Academic Appointments


Administrative Appointments


  • Chairman, Department of Cardiothoracic Surgery - Stanford (1993 - 2005)
  • Cardiac Surgeon-in-Charge, Johns Hopkins Hospital (1982 - 1992)

Professional Education


  • MD, Yale School of Medicine, Medicine (1970)
  • BS, Stanford University, Physiology (1966)

Current Research and Scholarly Interests


Mechanism of allograft rejection for the heart and, lung; late chronic effects of rejection, such as graft coronary, atherosclerosis in the heart and bronchiolitis obliterans in the, lung; treatment of rejection, including pharmacologic agents, total, lymphoid irradiation, and the induction of tolerance in fetal, animals; clinical studies include the results of lung and heart-lung, transplantation, modification of immunosuppressive protocols, and, factors contributing to late chronic rejection.

2018-19 Courses


All Publications


  • Combined heart lung transplantation: an updated review of the current literature. Transplantation Pasupneti, S., Dhillon, G., Reitz, B., Khush, K. 2017

    Abstract

    Heart lung transplantation is a viable treatment option for patients with many end stage heart and lung pathologies. However, given the complex nature of the procedure, it is imperative that patients are selected appropriately and the clinician is aware of the many unique aspects in management of this population. This review seeks to describe updated organ selection policies, peri and postoperative management strategies, monitoring of graft function, and clinical outcomes for patients following combined heart-lung transplantation in the current era.

    View details for DOI 10.1097/TP.0000000000001820

    View details for PubMedID 28505026

  • Changes in Risk Profile Over Time in the Population of a Pediatric Heart Transplant Program. Annals of thoracic surgery Reinhartz, O., Maeda, K., Reitz, B. A., Bernstein, D., Luikart, H., Rosenthal, D. N., Hollander, S. A. 2015; 100 (3): 989-994

    Abstract

    Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time.We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10 years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed.Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease.The risk profile of pediatric transplant patients in our institution has increased over time. In the last 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

    View details for DOI 10.1016/j.athoracsur.2015.05.111

    View details for PubMedID 26228604

  • Changes in Risk Profile Over Time in the Population of a Pediatric Heart Transplant Program. Annals of thoracic surgery Reinhartz, O., Maeda, K., Reitz, B. A., Bernstein, D., Luikart, H., Rosenthal, D. N., Hollander, S. A. 2015; 100 (3): 989-995

    Abstract

    Single-center data on pediatric heart transplantation spanning long time frames is sparse. We attempted to analyze how risk profile and pediatric heart transplant survival outcomes at a large center changed over time.We divided 320 pediatric heart transplants done at Stanford University between 1974 and 2014 into three groups by era: the first 20 years (95 transplants), the subsequent 10 years (87 transplants), and the most recent 10 years (138 transplants). Differences in age at transplant, indication, mechanical support, and survival were analyzed.Follow-up was 100% complete. Average age at time of transplantation was 10.4 years, 11.9 years, and 5.6 years in eras 1, 2, and 3, respectively. The percentage of infants who received transplants by era was 21%, 7%, and 18%, respectively. The indication of end-stage congenital heart disease vs cardiomyopathy was 24%, 22%, and 49%, respectively. Only 1 patient (1%) was on mechanical support at transplant in era 1 compared with 15% in era 2 and 30% in era 3. Overall survival was 72% at 5 years and 57% at 10 years. Long-term survival increased significantly with each subsequent era. Patients with cardiomyopathy generally had a survival advantage over those with congenital heart disease.The risk profile of pediatric transplant patients in our institution has increased over time. In the last 10 years, median age has decreased and ventricular assist device support has increased dramatically. Transplantation for end-stage congenital heart disease is increasingly common. Despite this, long-term survival has significantly and consistently improved.

    View details for DOI 10.1016/j.athoracsur.2015.05.111

    View details for PubMedID 26228604

  • Elevated pretransplant pulmonary vascular resistance index does not predict mortality after isolated orthotopic heart transplantation in children: A retrospective analysis of the UNOS database PEDIATRIC TRANSPLANTATION Chiu, P., Schaffer, J. M., Sheikh, A. Y., Ha, R., Reinhartz, O., Mainwaring, R., Reitz, B. A. 2015; 19 (6): 623-633

    Abstract

    OHT is the definitive therapy in end-stage heart failure. Elevated PVRI is considered a relative contraindication to isolated OHT; this assumption is re-evaluated using data from the UNOS database. A retrospective review of de-identified data from the UNOS dataset was performed. There were 1943 pediatric OHT recipients between 10/87 and 12/11 with sufficient data for analysis. Cox regression was performed to examine the effect of baseline characteristics on post-transplant survival. Patients were propensity matched, and Kaplan-Meier survival analysis was performed comparing cohorts of patients using thresholds of 6 and 9 WU × m(2) . PVRI was not a significant predictor of post-transplant outcomes in either univariate or multivariate Cox regression. Kaplan-Meier analysis revealed no difference in survival between both unmatched and propensity-matched OHT recipients. In conclusion, elevated PVRI was not associated with post-transplant mortality in pediatric OHT recipients. A prospective study assessing the current use of PVRI ≥6 as a threshold to contraindicate isolated OHT should be undertaken. Removing this potentially unnecessary restriction on transplant candidacy may make this life-saving therapy available to a greater number of patients.

    View details for DOI 10.1111/petr.12550

    View details for Web of Science ID 000358688400018

  • Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy. Journal of cardiology Sedehi, D., Finocchiaro, G., Tibayan, Y., Chi, J., Pavlovic, A., Kim, Y. M., Tibayan, F. A., Reitz, B. A., Robbins, R. C., Woo, J., Ha, R., Lee, D. P., Ashley, E. A. 2015; 66 (1): 57-62

    Abstract

    Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM.We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations.Surgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population.Long-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

    View details for DOI 10.1016/j.jjcc.2014.08.010

    View details for PubMedID 25238885

  • Long-term outcomes of septal reduction for obstructive hypertrophic cardiomyopathy JOURNAL OF CARDIOLOGY Sedehi, D., Finocchiaro, G., Tibayan, Y., Chi, J., Pavlovic, A., Kim, Y. M., Tibayan, F. A., Reitz, B. A., Robbins, R. C., Woo, J., Ha, R., Lee, D. P., Ashley, E. A. 2015; 66 (1-2): 57-62

    Abstract

    Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM.We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations.Surgical myectomy improved NYHA class (2.74±0.65 to 1.54±0.74, p<0.001), reduced resting gradient (67.4±43.4mmHg to 11.2±16.4mmHg, p<0.001), and inducible LVOT gradient (98.1±34.7mmHg to 33.6±34.9mmHg, p<0.001). Similarly, ASA improved functional class (2.99±0.35 to 1.5±0.74, p<0.001), resting gradient (67.1±26.9mmHg to 23.9±29.4mmHg, p<0.001) and provoked gradient (104.4±34.9mmHg to 35.5±38.6mmHg, p<0.001). Survival after myectomy at 5, 10, 15, and 20 years of follow-up was 92.9%, 81.1%, 68.9%, and 47.5%, respectively. Of note, long-term survival after myectomy was lower than for the general population [standardized mortality ratio (SMR)=1.40, p<0.005], but still compared favorably with historical data from non-operated HCM patients. Survival after ASA at 2 and 5 years was 97.8% and 94.7%, respectively. Short-term (5 year) survival after ASA (SMR=0.61, p=0.48) was comparable to that of the general population.Long-term follow-up of septal reduction strategies in obstructive HCM reveals that surgical myectomy and ASA are effective for symptom relief and LVOT gradient reduction and are associated with favorable survival. While overall prognosis for the community HCM population is similar to the general population, the need for surgical myectomy may identify a sub-group with poorer long-term prognosis. We await long-term outcomes of more extensive myectomy approaches adopted in the past 10 years at major institutions.

    View details for DOI 10.1016/j.jjcc.2014.08.010

    View details for Web of Science ID 000359684600010

  • Single- vs double-lung transplantation in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis since the implementation of lung allocation based on medical need. JAMA Schaffer, J. M., Singh, S. K., Reitz, B. A., Zamanian, R. T., Mallidi, H. R. 2015; 313 (9): 936-948

    Abstract

    Outcomes of single- and double-lung transplantation have not been rigorously assessed since the allocation of donor lungs according to medical need as quantified by the Lung Allocation Score, which began in 2005.To compare outcomes in single- and double-lung transplant recipients since the Lung Allocation Score was implemented.In this exploratory analysis, adults with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) who underwent lung transplantation in the United States between May 4, 2005, and December 31, 2012, were identified in the United Network for Organ Sharing thoracic registry, with follow-up to December 31, 2012. Posttransplantation graft survival was assessed with Kaplan-Meier analysis. Propensity scores were used to control for treatment selection bias. A multivariable flexible parametric prognostic model was used to characterize the time-varying hazard associated with single- vs double-lung transplantation.Single- or double-lung transplantation.Composite of posttransplant death and graft failure (retransplantation).Patients with IPF (n = 4134, of whom 2010 underwent single-lung and 2124 underwent double-lung transplantation) or COPD (n = 3174, of whom 1299 underwent single-lung and 1875 underwent double-lung transplantation) were identified as having undergone lung transplantation since May 2005. Median follow-up was 23.5 months. Of the patients with IPF, 1380 (33.4%) died and 115 (2.8%) underwent retransplantation; of the patients with COPD, 1138 (34.0%) died and 59 (1.9%) underwent retransplantation. After confounders were controlled for with propensity score analysis, double-lung transplants were associated with better graft survival in patients with IPF (adjusted median survival, 65.2 months [interquartile range {IQR}, 21.4-91.3 months] vs 50.4 months [IQR, 17.0-87.5 months]; P < .001) but not in patients with COPD (adjusted median survival, 67.7 months [IQR, 25.2-89.6 months] vs 64.0 months [IQR, 25.2-88.7 months]; P = .23). The interaction between diagnosis type (COPD or IPF) and graft failure was significant (P = .049). Double-lung transplants had a time-varying association with graft survival; a decreased instantaneous late hazard for death or graft failure among patients with IPF was noted at 1 year and persisted at 5 years postoperatively (instantaneous hazard at 5 years, hazard ratio, 0.67 [95% CI, 0.52-0.84] in patients with IPF and 0.89 [95% CI, 0.71-1.13] in patients with COPD).In an exploratory analysis of registry data since implementation of a medical need-based lung allocation system, double-lung transplantation was associated with better graft survival than single-lung transplantation in patients with IPF. In patients with COPD, there was no survival difference between single- and double-lung transplant recipients at 5 years.

    View details for DOI 10.1001/jama.2015.1175

    View details for PubMedID 25734735

  • Response to Letter Regarding Article Entitled "Heart and Combined Heart-Kidney Transplantation in Patients With Concomitant Renal Insufficiency and End-Stage Heart Failure'' AMERICAN JOURNAL OF TRANSPLANTATION SCHAFFER, J. M., Chiu, P., Singh, S. K., Oyer, P. E., Reitz, B. A., Mallidi, H. R. 2014; 14 (8): 1948-1949

    View details for DOI 10.1111/ajt.12817

    View details for Web of Science ID 000339433100037

    View details for PubMedID 25041450

  • Response to letter regarding article, "transplantation for idiopathic pulmonary arterial hypertension: improvement in the lung allocation score era". Circulation Schaffer, J. M., Singh, S. K., Joyce, D. L., Reitz, B. A., Robbins, R. C., Zamanian, R. T., Mallidi, H. R. 2014; 129 (16)

    View details for DOI 10.1161/CIRCULATIONAHA.113.007272

    View details for PubMedID 24753555

  • Combined Heart-Liver Transplantation in the MELD Era: Do Waitlisted Patients Require Exception Status? American journal of transplantation SCHAFFER, J. M., Chiu, P., Singh, S. K., Oyer, P. E., Reitz, B. A., Mallidi, H. R. 2014; 14 (3): 647-659

    Abstract

    Combined heart-liver transplant (HLT) is a viable therapy for patients with concomitant end-stage heart and liver failure. Using data from the United Network for Organ Sharing database, we examined the cumulative incidences of transplant and mortality in waitlisted candidates for HLT, isolated heart transplant (HRT) and isolated liver transplant (LIV) in the Model for End-Stage Liver Disease era. The incidence of waitlist mortality was higher in HLT candidates than in HRT candidates (p = 0.001, 26% vs. 12% at 1 year) or LIV candidates (p = 0.005, 26% vs. 14% at 1 year). These differences persisted after stratifying by disease severity. Posttransplant survival was not significantly different between HLT and HRT recipients or between HLT and LIV recipients. In a multivariable model, undergoing HLT was associated with enhanced survival for HLT candidates (hazard ratio, 0.41; confidence interval, 0.21-0.79; p = 0.008), but undergoing HRT alone was not. Interestingly, 90% of HLT recipients were allocated an organ locally, compared to 60% of HRT candidates and 73% of LIV candidates (both p < 0.001). These data suggest that the current cardiac and liver allocation systems may underestimate the risk of death for patients with concomitant end-stage heart and liver failure on the HLT waitlist.

    View details for DOI 10.1111/ajt.12595

    View details for PubMedID 24517245

  • Heart and combined heart-kidney transplantation in patients with concomitant renal insufficiency and end-stage heart failure. American journal of transplantation SCHAFFER, J. M., Chiu, P., Singh, S. K., Oyer, P. E., Reitz, B. A., Mallidi, H. R. 2014; 14 (2): 384-396

    Abstract

    In patients with end-stage heart failure (ESHF) who are candidates for isolated heart transplant (HRT), dialysis dependence (DD) is considered an indication for combined heart-kidney transplantation (HKT). HKT remains controversial in ESHF transplant candidates with nondialysis-dependent renal insufficiency (NDDRI). Using United Network for Organ Sharing data, we examined the cumulative incidences of transplant and mortality in patients with DD and NDDRI waitlisted for HKT or HRT. In all groups, 3-month waitlist mortality was dismal: 31% and 21% for HRT- and HKT-listed patients with DD and 12% and 7% for HRT- and HKT-listed patients with NDDRI. Five-year posttransplant survival was improved in HKT recipients compared with HRT recipients for both patients with DD (73% vs. 51%, p < 0.001) and NDDRI (80% vs. 69%, p < 0.001). Likewise, multivariable analysis associated HKT with better outcomes than HRT in HKT-listed patients, although both improved survival. These data argue strongly for HKT in ESHF transplant candidates with DD. However, in patients with NDDRI, HKT must be weighed against the possibility of renal recovery with isolated HRT. Whether HRT (followed by a staged kidney transplant in patients who do not recover renal function after HRT), as opposed to HKT, maximizes organ benefit for patients with NDDRI and ESHF requires assessment. Nevertheless, given their dismal waitlist outcomes and excellent posttransplant results, we suggest that patients with DD and NDDRI with ESHF be considered for early listing and transplant.

    View details for DOI 10.1111/ajt.12522

    View details for PubMedID 24279876

  • Adoption and Effectiveness of Internal Mammary Artery Grafting in Coronary Artery Bypass Surgery Among Medicare Beneficiaries JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Hlatky, M. A., Boothroyd, D. B., Reitz, B. A., Shilane, D. A., Baker, L. C., Go, A. S. 2014; 63 (1): 33-39

    Abstract

    The aim of this study was to assess the pattern of the adoption of internal mammary artery (IMA) grafting in the United States, test its association with clinical outcomes, and assess whether its effectiveness differs in key clinical subgroups.The effect of IMA grafting on major clinical outcomes has never been tested in a large randomized trial, yet it is now a quality standard for coronary artery bypass graft (CABG) surgery.We identified Medicare beneficiaries ≥66 years of age who underwent isolated multivessel CABG between 1988 and 2008, and we documented patterns of IMA use over time. We used a multivariable propensity score to match patients with and without an IMA and compared rates of death, myocardial infarction (MI), and repeat revascularization. We tested for variations in IMA effectiveness with treatment × covariate interaction tests.The IMA use in CABG rose slowly from 31% in 1988 to 91% in 2008, with persistent wide geographic variations. Among 60,896 propensity score-matched patients over a median 6.8-year follow-up, IMA use was associated with lower all-cause mortality (adjusted hazard ratio: 0.77, p < 0.001), lower death or MI (adjusted hazard ratio: 0.77, p < 0.001), and fewer repeat revascularizations over 5 years (8% vs. 9%, p < 0.001). The association between IMA use and lower mortality was significantly weaker (p ≤ 0.008) for older patients, women, and patients with diabetes or peripheral arterial disease.Internal mammary artery grafting was adopted slowly and still shows substantial geographic variation. IMA use is associated with lower rates of death, MI, and repeat coronary revascularization.

    View details for DOI 10.1016/j.jacc.2013.08.1632

    View details for Web of Science ID 000329838300007

    View details for PubMedID 24080110

    View details for PubMedCentralID PMC3947230

  • Transplantation for Idiopathic Pulmonary Arterial Hypertension Improvement in the Lung Allocation Score Era CIRCULATION Schaffer, J. M., Singh, S. K., Joyce, D. L., Reitz, B. A., Robbins, R. C., Zamanian, R. T., Mallidi, H. R. 2013; 127 (25): 2503-2513

    Abstract

    BACKGROUND: Lung transplant (LUT) and heart-lung transplant (HLT) represent surgical options for treating medically refractory idiopathic pulmonary arterial hypertension (IPAH). The effect of the lung allocation score (LAS) on waitlist and transplant outcomes in IPAH patients is poorly described. METHODS AND RESULTS: Adults diagnosed with IPAH and listed for transplant in the 80 months before and after the LAS algorithm was implemented (N=1430) were identified in the United Network for Organ Sharing thoracic registry. Patients were stratified by organ listed and pre- and post-LAS era. The cumulative incidences of transplant and mortality for waitlisted patients in both eras were appraised with competing outcomes analysis. Post-transplant survival was assessed with the Kaplan-Meier method. These analyses were repeated in propensity-matched subgroups. Cox proportional hazards analysis evaluated the effect of pre-listing and pre-transplant characteristics on mortality. We found that post-LAS-era patients had significantly worse comorbidities; nevertheless, both LUT and HLT candidates in this era enjoyed lower waitlist mortality and a higher incidence of transplant in our unmatched and propensity-matched analyses. On multivariable analysis, HLT and double-lung transplant (DLT) were associated with improved survival from the time of waitlisting, as was being listed at a medium-to-high-volume institution. Donor/recipient gender matching predicted post-transplant survival. CONCLUSIONS: The incidence of transplant has increased while waitlist mortality has decreased in IPAH patients waitlisted for transplant in the post-LAS era. Both HLT and DLT are predictive of survival in transplant candidates with IPAH, as is being listed at a medium-to-high-volume institution. Donor/recipient gender-matching is associated with better post-transplant survival.

    View details for DOI 10.1161/CIRCULATIONAHA.112.001080

    View details for Web of Science ID 000320916900014

    View details for PubMedID 23697910

  • Heart transplant graft survival is improved after a reduction in panel reactive antibody activity. journal of thoracic and cardiovascular surgery Schaffer, J. M., Singh, S. K., Reitz, B. A., Oyer, P. E., Robbins, R. C., Mallidi, H. R. 2013; 145 (2): 555-564

    Abstract

    Allosensitization in potential orthotopic heart transplant recipients is evaluated with the panel reactive antibody assay. Sensitized patients have prolonged wait times and increased waitlist and post-transplant mortality. Although low panel reactive antibody activity at the time of orthotopic heart transplantation is associated with improved outcomes, literature regarding the survival benefit of a panel reactive antibody reduction in the sensitized orthotopic heart transplant recipient remains limited.Adult orthotopic heart transplant recipients listed in the United Network for Organ Sharing database (October 1, 1987, to June 29, 2004) were stratified by peak panel reactive antibody activity and whether a substantial decline from peak to most recent panel reactive antibody activity occurred before transplant. Propensity matching adjusted for differences in recipient and donor characteristics. Graft survival was assessed with Kaplan-Meier analysis. Cox proportional hazards regression determined predictors of graft survival.Pretransplant characteristics differed between sensitized patients who had a substantial decline in panel reactive antibody activity and those who did not. Propensity matching compensated for these differences. Kaplan-Meier survival analysis of matched groups showed that the median graft survival was 120 months in patients with a significant panel reactive antibody reduction and 103 months in patients with a trivial reduction (P = .007, log-rank). In Cox proportional hazards modeling, a significant reduction in panel reactive antibody activity had an independent protective effect on graft survival (hazard ratio, 0.88; confidence interval, 0.80-0.96; P = .006).Sensitized patients who had a substantial reduction in panel reactive antibody activity had an associated decline in the incidence of graft failure compared with those without a panel reactive antibody activity reduction. These results support efforts to reduce panel reactive antibody activity before orthotopic heart transplantation in patients with high panel reactive antibody activity.

    View details for DOI 10.1016/j.jtcvs.2012.10.025

    View details for PubMedID 23246047

  • The first successful combined heart-lung transplantation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Reitz, B. A. 2011; 141 (4): 867-869

    View details for DOI 10.1016/j.jtcvs.2010.12.014

    View details for Web of Science ID 000288541300003

    View details for PubMedID 21419898

  • Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-Defined Morbidity and Mortality Associated With Pediatric Ventricular Assist Device Support at a Single US Center The Stanford Experience CIRCULATION-HEART FAILURE Stein, M. L., Robbins, R., Sabati, A. A., Reinhartz, O., Chin, C., Liu, E., Bernstein, D., Roth, S., Wright, G., Reitz, B., Rosenthal, D. 2010; 3 (6): 682-688

    Abstract

    The use of ventricular assist devices (VADs) to bridge pediatric patients to heart transplantation has increased dramatically over the last 15 years. In this report, we present the largest US single-center report of pediatric VAD use to date. We present detailed descriptions of morbidity and mortality associated with VAD support, using standard Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria for pediatrics to facilitate the comparison of these results to other studies.We retrospectively identified 25 patients younger than 18 years with 27 episodes of mechanical circulatory support using VADs as bridge to heart transplantation from January 1998 to December 2007. Survival to transplant for the entire cohort was 74%. The most common major morbidities, as defined by INTERMACS criteria for a pediatric population, were respiratory failure, major localized infections, major bleeding events, hepatic dysfunction, and right heart failure. Major neurological events occurred in 48% of the study population. The median time to the first occurrence of an adverse event was less than 14 days for respiratory failure, right heart failure, major localized infection, and major bleeding. Patients who died before transplantation had significantly more adverse events per day of support than did those who were successfully transplanted. Episodes of major bleeding, tamponade, acute renal failure, respiratory failure, and right heart failure were all associated with increased risk of mortality.INTERMACS criteria can be successfully used to analyze pediatric VAD outcomes. These data serve as a baseline for future studies of VAD support in children and indicate good survival rates but considerable morbidity.

    View details for DOI 10.1161/CIRCHEARTFAILURE.109.918672

    View details for Web of Science ID 000284261600011

    View details for PubMedID 20807863

  • Case report: a thrombus in the venous reservoir while using bivalirudin in a patient with heparin-induced thrombocytopenia undergoing heart transplantation. Anesthesia and analgesia Wong, J. K., Tian, Y., Shuttleworth, P., Caffarelli, A. D., Reitz, B. A., Mora-Mangano, C. T. 2010; 111 (3): 609-612

    Abstract

    Direct thrombin inhibitors are heparin alternatives for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. We report a case of a large thrombus forming in the venous reservoir while using bivalirudin. We suggest that blood stasis associated with the full venous reservoir maintained in this case led to formation of a large thrombus at the top of the venous canister. Furthermore, activated clotting times may not accurately reflect the magnitude of anticoagulation when using direct thrombin inhibitors.

    View details for DOI 10.1213/ANE.0b013e3181e9ead3

    View details for PubMedID 20686010

  • A Thrombus in the Venous Reservoir While Using Bivalirudin in a Patient with Heparin-Induced Thrombocytopenia Undergoing Heart Transplantation ANESTHESIA AND ANALGESIA Wong, J. K., Tian, Y., Shuttleworth, P., Caffarelli, A. D., Reitz, B. A., Mora-Mangano, C. T. 2010; 111 (3): 609-612

    Abstract

    Direct thrombin inhibitors are heparin alternatives for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. We report a case of a large thrombus forming in the venous reservoir while using bivalirudin. We suggest that blood stasis associated with the full venous reservoir maintained in this case led to formation of a large thrombus at the top of the venous canister. Furthermore, activated clotting times may not accurately reflect the magnitude of anticoagulation when using direct thrombin inhibitors.

    View details for DOI 10.1213/ANE.0b013e3181e9ead3

    View details for Web of Science ID 000281150100005

  • Review of Heart-Lung Transplantation at Stanford ANNALS OF THORACIC SURGERY Deuse, T., Sista, R., Weill, D., Tyan, D., Haddad, F., Dhillon, G., Robbins, R. C., Reitz, B. A. 2010; 90 (1): 329-337

    Abstract

    Long-term survival after heart-lung transplantation was first achieved in 1981 at Stanford and a total of 217 heart-lung transplantations had been performed by June 2008. This review summarizes Stanford's cumulative experience with heart-lung transplantation, demonstrates the progress that has been made, and discusses past and persistent problems. Diagnostic tools and treatment options for infectious diseases and rejection have changed and patient survival markedly improved over the almost three decades. Eight patients lived longer than 20 years. Further options to treat infections and strategies to control bronchiolitis obliterans syndrome, the main causes of early and long-term mortality, respectively, are required to achieve routine long-term survival.

    View details for DOI 10.1016/j.athoracsur.2010.01.023

    View details for Web of Science ID 000278998400070

    View details for PubMedID 20609821

  • Heart transplantation in situs inversus totalis JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Deuse, T., Reitz, B. A. 2010; 139 (2): 501-503

    View details for DOI 10.1016/j.jtcvs.2008.12.011

    View details for Web of Science ID 000274014300037

    View details for PubMedID 19660287

  • Outcomes of Septal Myectomy and Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy: The Stanford Experience 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Tibayan, Y., Sedehi, D., Chi, J., Pavlovic, A., Salisbury, H., Wheeler, M., Ho, M. Y., Sgroi, M., Kim, Y., Tibayan, F. A., Reitz, B. A., Robbins, R. C., Lee, D. P., Ashley, E. A. LIPPINCOTT WILLIAMS & WILKINS. 2009: S864–S864
  • Alternative Technique for Salvage of Donor Lungs With Insufficient Atrial Cuffs ANNALS OF THORACIC SURGERY Yarbrough, W. M., Bates, M. J., Deuse, T., Tang, D. G., Robbins, R. C., Reitz, B. A., Mallidi, H. R. 2009; 88 (4): 1374-1376

    Abstract

    Inadequate left atrial cuff surrounding donor pulmonary veins may present a technical challenge for successful lung transplantation. A simple technique for construction of venous anastomoses during lung transplantation when donor atrial cuff is lacking involves circumferential incorporation of surrounding donor pericardium into the anastomosis without directly suturing or augmenting donor venous structures.

    View details for DOI 10.1016/j.athoracsur.2008.11.031

    View details for Web of Science ID 000270388500066

    View details for PubMedID 19766854

  • Heart-Lung Transplantation In Situs Inversus Totalis ANNALS OF THORACIC SURGERY Deuse, T., Reitz, B. A. 2009; 88 (3): 1002-1003

    Abstract

    Situs inversus totalis is a condition with left-to-right reversal of the viscera combined with dextrocardia. It has long been regarded a contraindication for thoracic transplantation. Reconstruction of the mirror-image systemic venous pathways to accommodate normal donor organs remains the main surgical challenge. Here we present our simplified surgical technique for combined heart-lung transplantation and provide a concise review of the literature.

    View details for DOI 10.1016/j.athoracsur.2009.01.060

    View details for Web of Science ID 000269150500050

    View details for PubMedID 19699943

  • Dexmedetomidine and the Reduction of Postoperative Delirium after Cardiac Surgery PSYCHOSOMATICS Maldonado, J. R., Wysong, A., van der Starre, P. J., Block, T., Miller, C., Reitz, B. A. 2009; 50 (3): 206-217

    Abstract

    Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances.The authors investigated the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures.Patients underwent elective cardiac surgery with a standardized intraoperative anesthesia protocol, followed by random assignment to one of three postoperative sedation protocols: dexmedetomidine, propofol, or midazolam.The incidence of delirium for patients receiving dexmedetomidine was 3%, for those receiving propofol was 50%, and for patients receiving midazolam, 50%. Patients who developed postoperative delirium experienced significantly longer intensive-care stays and longer total hospitalization.The findings of this open-label, randomized clinical investigation suggest that postoperative sedation with dexmedetomidine was associated with significantly lower rates of postoperative delirium and lower care costs.

    View details for Web of Science ID 000267537700004

    View details for PubMedID 19567759

  • Use of INTERMACS Criteria To Assess Major Clinical Outcomes In Children Bridged to Heart Transplant Using Mechanical Circulatory Support 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation Stein, M. L., Robbins, R., Sabati, A., Reinhartz, O., Chin, C., Liu, E., Bernstein, D., Roth, S., Wright, G., Reitz, B. ELSEVIER SCIENCE INC. 2009: S207–S208
  • Twenty-year survivors of heart transplantation at Stanford University AMERICAN JOURNAL OF TRANSPLANTATION Deuse, T., Haddad, F., Pham, M., Hunt, S., Valantine, H., BATES, M. J., Mallidi, H. R., Oyer, P. E., Robbins, R. C., Reitz, B. A. 2008; 8 (9): 1769-1774

    Abstract

    Human heart transplantation started 40 years ago. Medical records of all cardiac transplants performed at Stanford were reviewed. A total of 1446 heart transplantations have been performed between January 1968 and December 2007 with an increase of 1-year survival from 43.1% to 90.2%. Sixty patients who were transplanted between 1968 and 1987 were identified who survived at least 20 years. Twenty-year survivors had a mean age at transplant of 29.4 +/- 13.6 years. Rejection-free and infection-free 1-year survivals were 14.3% and 18.8%, respectively. At their last follow-up, 86.7% of long-term survivors were treated for hypertension, 28.3% showed chronic renal dysfunction, 6.7% required hemodialysis, 10% were status postkidney transplantation, 13.3% were treated for diabetes mellitus, 36.7% had a history of malignancy and 43.3% had evidence of allograft vasculopathy. The half-life conditional on survival to 20 years was 28.1 years. Eleven patients received a second heart transplant after 11.9 +/- 8.0 years. The most common causes of death were allograft vasculopathy (56.3%) and nonlymphoid malignancy (25.0%). Twenty-year survival was achieved in 12.5% of patients transplanted before 1988. Although still associated with considerable morbidity, long-term survival is expected to occur at much higher rates in the future due to major advances in the field over the past decade.

    View details for DOI 10.1111/j.1600-6143.2008.02310.x

    View details for Web of Science ID 000258401700004

    View details for PubMedID 18557718

  • Unexpected findings during the anesthetic management of a patient with a cardiac paraganglioma JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Soran, P. D., Akram, S., Mihm, F., Fleischmann, D., Reitz, B., van der Starre, P. 2008; 22 (4): 570-572

    View details for DOI 10.1053/j.jvca.2008.01.019

    View details for Web of Science ID 000258388100011

    View details for PubMedID 18662633

  • Pneumatic paracorporeal ventricular assist device in infants and children: Initial Stanford experience 27th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation Malaisrie, S. C., Pelletier, M. P., Yun, J. J., Sharma, K., Timek, T. A., Rosenthal, D. N., Wright, G. E., Robbins, R. C., Reitz, B. A. ELSEVIER SCIENCE INC. 2008: 173–77

    Abstract

    Mechanical circulatory support with the Berlin Heart EXCOR pediatric ventricular assist device (VAD) has been used successfully in Europe for children with cardiac failure. Eighty-seven devices have been placed in North America through February 2007. We describe our single-center experience in 8 children.Eight children (ages 4 to 55 months), with median weight of 9.6 kg and body surface area of 0.48 m(2), received the Berlin Heart VAD as a bridge to transplantation. All patients were in cardiogenic shock requiring multiple inotropes. Primary diagnoses were idiopathic dilated cardiomyopathy (n = 4), congenital heart disease (n = 3) and restrictive cardiomyopathy (n = 1). After device insertion, all patients were treated with an anti-coagulant (heparin or coumadin) and one or more platelet inhibitors (aspirin with clopidogrel or dipyridamole).Five patients received support with a left ventricular assist device (LVAD) and 3 with a biventricular device (BiVAD). Duration of support ranged from 2 to 234 days (median 57 days). Five patients (63%) were successfully bridged to transplantation; of these, 4 were discharged home and 1 died from early graft failure. Five patients developed post-operative neurologic events. Of these 5 events, 4 could be explained by embolism or hemorrhage. Device exchange was performed in 4 patients in the intensive care unit.In selected children, the Berlin Heart VAD can be used as a bridge to transplantation. In contrast to the published European experience, neurologic events occur frequently. Anti-coagulation and platelet inhibition strategies continue to evolve. Device exchange is technically feasible at the bedside and should be considered at the earliest visualization of thrombus formation.

    View details for DOI 10.1016/j.healun.2007.11.567

    View details for Web of Science ID 000253258800005

    View details for PubMedID 18267223

  • Epicardial ablation of postinfarction ventricular tachycardia with an externally irrigated catheter in a patient with mechanical aortic and mitral valves HEART RHYTHM Anh, D. J., Hsia, H. H., Reitz, B., Zei, P. 2007; 4 (5): 651-654

    View details for DOI 10.1016/j.hrthm.2007.01.011

    View details for Web of Science ID 000246188800016

    View details for PubMedID 17467636

  • Plasma cefazolin levels during cardiovascular surgery: Effects of cardiopulmonary bypass and profound hypothermic circulatory arrest JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Caffarelli, A. D., Holden, J. P., Baron, E. J., Lemmens, H. J., D'Souza, H., Yau, V., Olcott, C., Reitz, B. A., Miller, D. C., van der Starre, P. J. 2006; 131 (6): 1338-1343

    Abstract

    We sought to assess the effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on plasma cefazolin levels administered for antimicrobial prophylaxis in cardiovascular surgery.Four groups (10 patients per group) were prospectively studied: vascular surgery without cardiopulmonary bypass (group A), cardiac surgery with a cardiopulmonary bypass time of less than 120 minutes (group B), cardiac surgery with a cardiopulmonary bypass time of greater than 120 minutes (group C), and cardiac surgery with cardiopulmonary bypass and profound hypothermic circulatory arrest (group D). Subjects received cefazolin at induction and a second dose before wound closure. Arterial blood samples were obtained preceding cefazolin administration, at skin incision, hourly during the operation, and before redosing. Cefazolin plasma concentrations were determined by using a radial diffusion assay, with Staphylococcus aureus as the indicator microorganism. Cefazolin plasma concentrations were considered noninhibitory at 8 microg/mL or less, intermediate at 16 mug/mL, and inhibitory at 32 microg/mL or greater.In group A cefazolin plasma concentrations remained greater than 16 microg/mL during the complete surgical procedure. In group B cefazolin plasma concentrations diminished to 16 microg/mL or less in 30% of the patients but remained greater than 8 microg/mL. In group C cefazolin plasma concentrations decreased to less than 16 microg/mL in 60% of patients and were less than 8 microg/mL in 50% of patients. In group D cefazolin plasma concentrations reached 16 microg/mL in 66% of the patients but decreased to 8 microg/mL in only 1 patient.For patients undergoing cardiac surgery with a cardiopulmonary bypass time of greater than 120 minutes, a single dose of cefazolin before skin incision with redosing at wound closure does not provide targeted antimicrobial cefazolin plasma levels during the entire surgical procedure. Patients undergoing profound hypothermic circulatory arrest are better protected, but the described protocol of prophylaxis is not optimal.

    View details for DOI 10.1016/j.jtcvs.2005.11.047

    View details for Web of Science ID 000238023300024

    View details for PubMedID 16733167

  • Heterotopic heart transplant combined with postoperative sildenafil use for the treatment of restrictive cardiomyopathy ANNALS OF THORACIC SURGERY Al-Khaldi, A., Reitz, B. A., Zhu, H., Rosenthal, D. 2006; 81 (4): 1505-1507

    Abstract

    We report successful management of a 22-month-old child with restrictive cardiomyopathy and severe pulmonary hypertension using the heterotopic heart transplant technique. Additional lessons learned from postoperative management, including the novel use of Sildenafil (Viagra, Pfizer, NY) for controlling pulmonary arterial pressure are described.

    View details for DOI 10.1016/j.athoracsur.2005.02.069

    View details for Web of Science ID 000236239200062

    View details for PubMedID 16564308

  • Ten- and 20-year survivors of pediatric orthotopic heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Ross, M., Kouretas, P., Gamberg, P., Miller, J., Burge, M., Reitz, B., Robbins, R., Chin, C., Bernstein, D. 2006; 25 (3): 261-270

    Abstract

    Pediatric heart transplantation is entering its third decade, allowing for the first time an analysis of a large group of true long-term survivors, specifically children who have survived > or =10 years post-transplantation.Fifty-two patients < or =18 years, who had undergone heart transplantation at Stanford between August 1974 and June 1993 and survived > or =10 years, were retrospectively reviewed.Forty (77%) patients are currently alive. Thirteen survived >15 years and 5 >20 years (the longest being 26 years). Actuarial survival was 79.4% at 14 years and 53.1% at 20 years. Cardiomyopathy was the reason for transplantation in 71% and congenital heart disease (CHD) in 29%. At last evaluation, 71% were on a cyclosporine-based regimen and 23% a tacrolimus-based regimen; 33% were steroid-free. Twenty-seven percent were totally free from treatable rejection, 44% developed serious infections, 69% were receiving anti-hypertensives, and 8% required renal transplantation. Neoplasms occurred in 23%, graft coronary artery disease (CAD) in 31%, and 15% required re-transplantation. Of the 12 deaths, CAD was the most common cause (n = 4), followed by non-specific late graft failure (n = 3), infection (n = 2), rejection (n = 1), non-lymphoid cancer (n = 1) and lymphoid cancer (n = 1). Physical rehabilitation and return to normal lifestyle has been nearly 100%.Heart transplantation in pediatric patients is compatible with true long-term survival with a growing cohort of children approaching their second and third decades. The gradual constant-phase decrease in survival noted in earlier studies appears to be continuing. Rejection and infection are low but persistent risks after the first years. Graft CAD and non-specific late graft dysfunction are the leading causes of death after 10 years. Rehabilitation is excellent.

    View details for DOI 10.1016/j.healun.2005.09.011

    View details for Web of Science ID 000235946000001

    View details for PubMedID 16507417

  • Primary cardiac angiosarcoma: case report and review of the literature CARDIOVASCULAR PATHOLOGY Kurian, K. C., Weisshaar, D., Parekh, H., Berry, G. J., Reitz, B. 2006; 15 (2): 110-112

    Abstract

    We report of a young man who was referred for evaluation of the right atrial mass. He had presented outside the hospital with shortness of breath. A transthoracic echocardiogram (TTE) done there showed a bright echodensity in the right atrium with moderate pericardial effusion. He was treated for presumed viral pericarditis. Pericardiocentesis showed a bloody effusion. Four weeks after this initial presentation, a repeat TTE was done to evaluate for recurrent pericardial effusion due to shortness of breath. The right atrial mass had increased in size and no effusion was noted. He was referred to us for further evaluation. The tumor was successfully resected during surgery, and the pathological examination revealed primary cardiac angiosarcoma. The case highlights the misdiagnosis in initial clinical presentation, current diagnostic modalities, and treatment options for cardiac angiosarcoma.

    View details for DOI 10.1016/j.carpath.2005.10.003

    View details for Web of Science ID 000236664600007

    View details for PubMedID 16533700

  • "One-and-half ventricle" cardiac transplantation for complex congenital heart disease. Clinical transplants Sharma, K., Reitz, B. A. 2006: 564-565

    View details for PubMedID 18365436

  • Combined use of the JAK3 inhibitor CP-690,550 with mycophenolate mofetil to prevent kidney allograft rejection in nonhuman primates TRANSPLANTATION Borie, D. C., Larson, M. J., Flores, M. G., Campbell, A., Rousvoal, G., Zhang, S., Higgins, J. P., Ball, D. J., Kudlacz, E. M., Brissette, W. H., Elliott, E. A., Reitz, B. A., Changelian, P. S. 2005; 80 (12): 1756-1764

    Abstract

    Immunosuppression via Janus kinase (JAK) 3 inhibition affords significant prolongation of allograft survival. We investigated the effects of an immunosuppressive regimen combining the JAK3 inhibitor CP-690,550 with mycophenolate mofetil (MMF) in nonhuman primates (NHPs).Life-supporting kidney transplantations were performed between ABO-compatible, MLR-mismatched NHPs. Animals were treated orally twice a day with CP-690,550 and MMF (n=8) or MMF alone (n=2) and were euthanized at day 90 or earlier due to allograft rejection.Mean survival time (+/-SEM) in animals treated with MMF alone (23+/-1 days) was significantly extended in animals that concurrently received CP-690,550 (59.5+/-9.8 days, P=0.02). Combination animals exposed to higher levels of CP-690,550 had a significantly better survival (75.2+/-8.7 days) than animals that received less CP-690,550 (33.3+/-12.6 days, P=0.02). Three combination therapy animals were euthanized at day 90 with a subnormal renal function and early-stage acute graft rejection. Rejection, delayed by treatment, ultimately developed in other animals. Anemia and gastrointestinal intolerance was seen in combination therapy animals that otherwise did not show evidence of viral or bacterial infection besides signs consistent with subclinical pyelonephritis (n=3). One incidental lymphosarcoma was noted.Addition of CP-690,550 to MMF significantly improved allograft survival. The observed side effects appear amenable to improvements upon alteration of dosing strategies. Efficacy of this combination regimen suggests that it could become the backbone of calcineurin inhibitor-free regimens.

    View details for DOI 10.1097/01.tp.0000184634.25042.ea

    View details for Web of Science ID 000234364200021

    View details for PubMedID 16378072

  • Effects of JAK3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts TRANSPLANTATION Paniagua, R., Si, M. S., Flores, M. G., Rousvoal, G., Zhang, S., Aalami, O., Campbell, A., Changelian, P. S., Reitz, B. A., Borie, D. C. 2005; 80 (9): 1283-1292

    Abstract

    Janus Kinase (JAK) 3 is a tyrosine kinase essential for proper signal transduction downstream of selected cytokine receptors and for robust T-cell and natural killer cells activation and function. JAK3 inhibition with CP-690,550 prevents acute allograft rejection. To provide further insight into the mechanisms of efficacy, we investigated the immunomodulatory effects of CP-690,550 in vitro and in vivo in nonhuman primates.Pharmacodynamic assessments of lymphocyte activation, function, proliferation and phenotype were performed in three settings: in vitro in whole blood isolated from untransplanted cynomolgus monkeys (cynos), in vivo in blood from untransplanted cynos dosed with CP-690,550 for 8 days, and in vivo in blood from transplanted cynos immunosuppressed with CP-690,550. Cell surface activation markers expression, IL-2- enhanced IFN-gamma production, lymphocyte proliferation and immune cell phenotype analyzes were performed with multiparametric flow cytometry.In vitro exposure to CP-690,550 resulted in significant reduction of IL-2-enhanced IFN-gamma production by T-cells (maximum inhibition of 55-63%), T-cell surface expression of CD25 (50% inhibitory concentration (IC50); 0.18 microM) and CD71 (IC50; 1.6 microM), and T-cell proliferative capacities measured by proliferating cell nuclear antigen expression (IC50; 0.87 microM). Similar results were observed in animals dosed with CP-690,550. In addition, transplanted animals displayed significant reduction of NK cell (90% from baseline) and T-cell numbers whereas CD8 effector memory T-cell populations were unaffected.Potent in vitro and in vivo immunomodulatory effects of the JAK3 inhibitor CP-690,550 likely contribute to its efficacy in the prevention of organ allograft rejection.

    View details for DOI 10.1097/01.tp.0000177643.05739.cd

    View details for Web of Science ID 000233732600021

    View details for PubMedID 16314797

  • Induction therapy for pediatric and adult heart transplantation: Comparison between OKT3 and daclizumab TRANSPLANTATION Chin, C., Pittson, S., Luikart, H., Bernstein, D., Robbins, R., Reitz, B., Oyer, P., Valantine, H. 2005; 80 (4): 477-481

    Abstract

    Induction therapy can reduce morbidity and early mortality in pediatric and adult heart transplant recipients. Monoclonal and polyclonal agents are most widely used; they nonspecifically deplete the T-cell pool and are thus associated with drug-induced side effects. The cytokine release syndrome is one of the most problematic events associated with induction. Daclizumab, a highly humanized, specific interleukin-2 receptor blocker, may be efficacious to the monoclonal agent, OKT3. Due to its specific action and properties, the safety profile of this agent may be superior to OKT3.Forty subjects received daclizumab and their clinical outcomes were compared against a historical group of 40 subjects who received OKT3. Three- and six-month outcome measures included survival, rejection history, steroid burden, and complications.Mortality was low between the groups with equivalent 6-month survival. No differences in rejection profile or time to the first significant rejection event were detected; no subject had severe acute rejection within the first 180 days. Steroid requirement for maintenance immunosuppression and treatment of rejection was also similar between the groups. Six-month prevalence for complications were significantly different; 55% of OKT3-treated subjects having at least one event compared to 33% of daclizumab-treated subjects (P=0.04). The likelihood of complications occurred within the first month after transplantation.Daclizumab induction therapy is as efficacious as OKT3 in the prevention of early acute rejection after heart transplantation among pediatric and adult subjects. Complications related to the induction agent are significantly lower in the humanized product.

    View details for DOI 10.1097/01.tp.0000168153.50774.30

    View details for Web of Science ID 000231566800008

    View details for PubMedID 16123721

  • Immunosuppression by the JAK3 inhibitor CP-690,550 delays rejection and significantly prolongs kidney allograft survival in nonhuman primates TRANSPLANTATION Borie, D. C., Changelian, P. S., Larson, M. J., Si, M. S., Paniagua, R., Higgins, J. P., Holm, B., Campbell, A., Lau, M., Zhang, S., Flores, M. G., Rousvoal, G., Hawkins, J., Ball, D. A., Kudlacz, E. M., Brissette, W. H., Elliott, E. A., Reitz, B. A., Morris, R. E. 2005; 79 (7): 791-801

    Abstract

    Janus kinase 3 (JAK3) mediates signal transduction from cytokine receptors using the common chain (gammac). Because mutations in genes encoding gammac or JAK3 result in immunodeficiency, we investigated the potential of a rationally designed inhibitor of JAK3, CP-690,550, to prevent renal allograft rejection in nonhuman primates.Life-supporting kidney transplantations were performed between mixed leukocyte reaction-mismatched, ABO blood group-matched cynomolgus monkeys. Animals were treated with CP-690,550 (n = 18) or its vehicle (controls, n = 3) and were euthanized at day 90 or earlier if there was allograft rejection.Mean survival time (+/- standard error of mean) in animals treated with CP-690,550 (53 +/- 7 days) was significantly longer than in control animals (7 +/- 1 days, P=0.0003) and was positively correlated with exposure to the drug (r = 0.79, P < 0.01). Four treated animals were euthanized at 90 days with a normal renal function and low-grade rejection at final pathology. Occurrence of rejection was significantly delayed in treated animals (46 +/- 7 days from transplantation vs. 7 +/- 1 days in controls, P = 0.0003). Persistent anemia, polyoma virus-like nephritis (n = 2), and urinary calcium carbonate accretions (n = 3) were seen in animals with high exposure. Natural killer cell and CD4 and CD8 T-cell numbers were significantly reduced in treated animals. Blood glucose, serum lipid levels, and arterial blood pressure were within normal range in treated animals, and no cancers were demonstrated.CP-690,550 is the first reported JAK3 inhibitor combining efficacy and good tolerability in a preclinical model of allotransplantation in nonhuman primates and thus has interesting potential for immunosuppression in humans.

    View details for DOI 10.1097/01.TP.0000157117.30290.6F

    View details for Web of Science ID 000228373100006

    View details for PubMedID 15818321

  • Lung transplantation: A decade of experience JOURNAL OF HEART AND LUNG TRANSPLANTATION Moffatt, S. D., Demers, P., Robbins, R. C., Doyle, R., Wienacker, A., Henig, N., Theodore, J., Reitz, B. A., Whyte, R. I. 2005; 24 (2): 145-151

    Abstract

    Over the past 3 decades, the field of lung transplantation has been refined. However, many barriers exist that limit long-term success. The purpose of this study was to review a single institution's long-term experience with single and double lung transplantation and to assess the effect of different immunosuppressive therapies on outcomes.Lung transplant recipients, both single and double, were reviewed, retrospectively. Patients were divided into five groups: group I, all lung transplants (n = 127); group II, single lung transplants (n = 73); group III, double lung transplants (n = 54); group IV, OKT3 induction therapy recipients (n = 27); and group V, RATG induction therapy recipients (n = 100). Rates of survival, rejection, bronchiolitis obliterans syndrome (BOS) and infection were analyzed at 1, 3, and 5 years.There were no significant differences in survival, acute rejection rate, freedom from BOS, nor infection between single and double lung transplant recipients. Induction therapy with RATG (group V) was associated with significantly improved survival and freedom from acute rejection, BOS, and infection when compared to OKT3 induction therapy (group IV).An earlier impression that RATG is superior to OKT3 induction therapy has borne true in terms of overall survival and incidence of BOS, acute rejection and infection rates. Lung transplantation, using RATG induction therapy, remains an important modality for end-stage pulmonary disease.

    View details for DOI 10.1016/j.healun.2003.10.020

    View details for Web of Science ID 000226922800005

    View details for PubMedID 15701428

  • Hyperacute rejection of hDAF-transgenic pig organ xenografts in cynomolgus monkeys: influence of pre-existing anti-pig antibodies and prevention by the alpha GAL glycoconjugate GAS914 XENOTRANSPLANTATION Lam, T. T., Hausen, B., Boeke-Purkis, K., Paniagua, R., Lau, M., Hook, L., Berry, G., Higgins, J., Duthaler, R. O., Katopodis, A. G., Robbins, R., Reitz, B., Borie, D., Schuurman, H. J., Morris, R. E. 2004; 11 (6): 517-524

    Abstract

    Our introductory pig-to-cynomolgus monkey heart or kidney transplantation using organs from pigs transgenic for human decay-accelerating factor (hDAF), showed a high incidence of hyperacute rejection (HAR), which was ascribed to extraordinary high levels of anti-pig antibodies. We evaluated the efficacy of GAS914, a Gal alpha 1-3Gal trisaccharide linked to a poly-l-lysine backbone, in inhibition of HAR.hDAF transgenic heterotopic heart (n = 15) or life-supporting kidney (n = 8) transplantation included induction with cyclophosphamide or anti-thymocyte globulin, and maintenance with cyclosporine or tacrolimus, steroids and mycophenolate sodium/mofetil. Four doses of GAS914 were given before transplantation. Rejection was confirmed by graft histology, and anti-pig antibody levels were determined in various assays.Four of six heart transplants without GAS914 treatment showed HAR. Nine subsequent transplants with GAS914 pre-treatment, did not show HAR (chi-square, P < 0.05). Two of four kidney transplants without GAS914 treatment ended with HAR. Four subsequent transplants with GAS914 did not show HAR. Animals with HAR showed extremely high antibody levels. Samples just before transplantation showed significantly higher antibody levels in recipients presenting with HAR. In all assays antibody levels were significantly lowered by GAS914 pre-treatment.HAR of hDAF solid organs could be ascribed to high levels of anti-pig antibodies. It is hypothesized that the hDAF transgene shows a threshold in efficacy, above which an overwhelming attack by antibodies and complement activation cannot be modulated to prevent HAR. HAR does not occur when animals with lower levels are used, or when antibodies are effectively depleted from the circulation by GAS914 treatment.

    View details for DOI 10.1111/j.1399-3089.2004.00173.x

    View details for Web of Science ID 000224432900005

    View details for PubMedID 15479461

  • Regression of severe pulmonary arteriovenous malformations after Fontan revision and "Hepatic factor" rerouting ANNALS OF THORACIC SURGERY Pike, N. A., Vricella, L. A., Feinstein, J. A., Black, M. D., Reitz, B. A. 2004; 78 (2): 697-699

    Abstract

    Although previously described in patients undergoing staged palliation for univentricular heart disease, the mechanism by which hepatic venous flow prevents development of pulmonary arteriovenous malformations is still not completely understood. We present a case in which successful H-type Fontan revision with rerouting of hepatic venous flow through a hemiazygous vein successfully reversed the progression of severe left pulmonary arteriovenous malformations.

    View details for DOI 10.1016/j.athorascur.2004.02.003

    View details for Web of Science ID 000222999300055

    View details for PubMedID 15276554

  • What's new in cardiac surgery JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Reitz, B. A. 2004; 198 (5): 784-797
  • Identifying cardiac transplant rejection in children: Diagnostic utility of echocardiography, right heart catheterization and endomyocardial biopsy data JOURNAL OF HEART AND LUNG TRANSPLANTATION Rosenthal, D. N., Chin, C., Nishimura, K., Perry, S. B., Robbins, R. C., Reitz, B., Bernstein, D., Feinstein, J. A. 2004; 23 (3): 323-329

    Abstract

    There has been a continued search for alternative diagnostic techniques that do not necessitate endomyocardial biopsy for diagnosing rejection in cardiac transplant recipients. The purpose of this study is to evaluate the role of echocardiography and hemodynamic catheterization data compared with endomyocardial biopsy results, in rejection surveillance for the pediatric heart transplant recipient.A prospective, blinded evaluation was performed utilizing echocardiographic and standard right heart catheterization parameters to predict acute rejection episodes.Forty-nine patients underwent 281 biopsies. Two groups were defined: those with Grade <2 rejection and those with grade > or =2 rejection. None of the echocardiographic variables showed significant differences between the study groups and all group data were within normal limits. Mixed venous saturation, mean right atrial pressure, right ventricular end-diastolic pressure and mean pulmonary artery pressure were found to be statistically significant between groups. Receiver-operator characteristic (ROC) curves were constructed to determine the extent to which the various parameters were clinically useful. The ROC found little clinical usefulness for all variables, including those found to be statistically significant.Differences in both echocardiographic and hemodynamic data were not clinically significant between the 2 groups of patients. Although many of the catheterization-derived parameters were statistically significant, they did not permit effective discrimination between groups. This is the only clinically relevant application of such data and may explain the conflicting previous reports. It is only through analyses such as ROC that the clinical application (or lack thereof) can be appreciated in this population.

    View details for DOI 10.1016/S1053-2498(03)00209-2

    View details for Web of Science ID 000220155700009

    View details for PubMedID 15019642

  • Obliterative bronchiolitis is prevented by JAK3 inhibition with the new immunosuppressant CP-690,550. 5th American Transplant Congress Rousvoal, G., Zhang, S., Larson, M., Berry, G., Si, M. S., Holm, B., Paniagua, R., Hawkins, J., Lau, M., Flores, M., Morris, R., Reitz, B., Borie, D. WILEY-BLACKWELL. 2004: 286–286
  • Superarray analysis of tracheal allografts under JAK3-targeted immunosuppression reveals a role for the B-cell chemoattractant BLC-BCA1. 5th American Transplant Congress Lau, M., Zhang, S., Larson, M., Flores, M., Si, M. S., Rousvoal, G., Hawkins, J., Holm, B., Berry, G., Morris, R., Reitz, B., Borie, D. WILEY-BLACKWELL. 2004: 197–197
  • In vitro evaluation of the effects of candidate immunosuppressive drugs: Flow cytometry and quantitative real-time PCR as two independent and correlated read-outs. 5th American Transplant Congress Flores, M., Zhang, S., Ha, A., Holm, B., Morris, R., Reitz, B., Borie, D. WILEY-BLACKWELL. 2004: 334–334
  • JAK3 inhibition as a new concept for immune suppression. Current opinion in investigational drugs Borie, D. C., Si, M., Morris, R. E., Reitz, B. A., Changelian, P. S. 2003; 4 (11): 1297-1303

    Abstract

    Although current immunosuppressive drugs are effective, they have numerous severe side effects that mandate the search for new agents. Mutations in the gene for janus kinase (JAK)3 result in severe combined immune deficiency with severely impaired humoral and cellular immunity, an observation that has prompted the development of JAK3 inhibitors. Due to its central role in lymphocyte activation, proliferation and homeostasis, targeting the JAK/signal transducer and activator of transcription (STAT) pathway may provide the required efficacy, without the toxicities associated with current therapies. Several studies conducted in rodents have validated the proof-of-concept, with a variety of JAK3 inhibitors demonstrating efficacy for immune suppression. In addition, the selective JAK3 inhibitor CP-690550 (Pfizer Inc) significantly improved allograft survival in a stringent preclinical model in primates and exhibited a good safety profile in non-human primates. This, along with studies of protein kinase inhibitors for cancer treatment, could demonstrate that development of effective, safe and selective kinase inhibitors for immunosuppression is possible.

    View details for PubMedID 14758768

  • Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor SCIENCE Changelian, P. S., Flanagan, M. E., Ball, D. J., Kent, C. R., Magnuson, K. S., Martin, W. H., Rizzuti, B. J., Sawyer, P. S., Perry, B. D., Brissette, W. H., McCurdy, S. P., Kudlacz, E. M., Conklyn, M. J., Elliott, E. A., Koslov, E. R., Fisher, M. B., Strelevitz, T. J., Yoon, K., Whipple, D. A., Sun, J. M., Munchhof, M. J., Doty, J. L., Casavant, J. M., Blumenkopf, T. A., Hines, M., Brown, M. F., Lillie, B. M., Subramanyam, C., Shang-Poa, C., MILICI, A. J., Beckius, G. E., Moyer, J. D., Su, C. Y., Woodworth, T. G., Gaweco, A. S., Beals, C. R., Littman, B. H., Fisher, D. A., Smith, J. F., Zagouras, P., Magna, H. A., Saltarelli, M. J., Johnson, K. S., Nelms, L. F., Des Etages, S. G., Hayes, L. S., Kawabata, T. T., Finco-Kent, D., Baker, D. L., Larson, M., Si, M. S., Paniagua, R., Higgins, J., Holm, B., Reitz, B., Zhou, Y. J., Morris, R. E., O'Shea, J. J., Borie, D. C. 2003; 302 (5646): 875-878

    Abstract

    Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.

    View details for Web of Science ID 000186258000052

    View details for PubMedID 14593182

  • Tolerability profile of the new JAK3 inhibitor CP-690,550: comparison to cyclosporine in renal transplantation of cynomolgus monkeys 89th Annual Clinical Congress of the American-College-of-Surgeons Si, M. S., Larson, M., Changelian, P., Lau, M., Flores, M., Paniagua, R., Holm, B., Morris, R., Reitz, B., Borie, D. ELSEVIER SCIENCE INC. 2003: S89–S89
  • Immunomodulatory effects of docetaxel on human lymphocytes INVESTIGATIONAL NEW DRUGS Si, M. S., Imagawa, D. K., Ji, P., Wei, X. B., Holm, B., Kwok, J., Lee, M., Reitz, B. A., Borie, D. C. 2003; 21 (3): 281-290

    Abstract

    Docetaxel is an antineoplastic taxoid that interferes with microtubule polymerization dynamics and is used clinically to treat advanced cancers. Because microtubules play significant roles in T lymphocyte activation and function we characterized the in vitro immunomodulatory properties of docetaxel. Effects of docetaxel on lectin-induced peripheral blood mononuclear cell (PBMC) proliferation were measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and proliferating cell nuclear antigen (PCNA) staining. In addition, apoptosis was measured by annexin V staining and cell activation by determination of CD25 and CD71 cell surface expression. Intracellular calcium kinetics in lectin-activated Jurkat T lymphocytes exposed to docetaxel were investigated. Th1 cytokine production was assessed in T lymphocytes by intracellular cytokine staining. Docetaxel significantly inhibited PBMC proliferation and promoted apoptosis of lectin-activated PBMCs. Docetaxel significantly decreased expression of CD71 but not that of CD25. Docetaxel altered intracellular calcium homeostasis but did not affect Th1 cytokine production in T lymphocytes. In conclusion we demonstrate that docetaxel, although exerting significant antiproliferative effects on lymphocytes and promoting activation-induced apoptosis does affect only partially lymphocyte activation and function and does not affect Th1 cytokine production. These results suggest maintenance of lymphocyte functions important for host tumor surveillance and suggest that this compound may have a role in the treatment of cancer arising organ transplant recipients.

    View details for Web of Science ID 000185010800003

    View details for PubMedID 14578678

  • Long-term results of heart transplantation in patients older than 60 years JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Demers, P., Moffatt, S., Oyer, P. E., Hunt, S. A., Reitz, B. A., Robbins, R. C. 2003; 126 (1): 224-231

    Abstract

    Advanced age has been traditionally considered a relative contraindication for heart transplantation. Older patients are now considered as potential candidates for heart transplantation. The objective of this study was to evaluate the long-term results of heart transplantation in patients older than 60 years.Between 1986 and 2001, 81 patients aged between 60 and 70 years (mean, 63 +/- 2 years) underwent heart transplantation. These patients were compared with 403 adult recipients younger than 60 years (mean, 47 +/- 11 years) who underwent transplantation during the same period.Thirty-day mortality was 6% (5/81) and 6% (25/403) in the older and younger patients, respectively (P = NS). Actuarial survival at 1, 5, and 10 years was 88% +/- 4% versus 83% +/- 2%, 75% +/- 5% versus 69% +/- 2%, and 50% +/- 9% versus 51% +/- 3% in the older and younger patients, respectively (P = NS). Older patients had significantly fewer rejection episodes (P =.003). Freedom from allograft coronary artery disease at 1, 5, and 10 years was 98% +/- 2% versus 92% +/- 2%, 85% +/- 6% versus 76% +/- 3%, and 81% +/- 7% versus 68% +/- 3% (P =.1). The incidences of infectious complication, cytomegalovirus infection, and posttransplant lymphoproliferative disorder were similar between the 2 groups, but older recipients were more likely to have a nonposttransplant lymphoproliferative disorder cancer (P =.002). Age at transplantation was not identified as an independent risk factor for early and late death.Heart transplantation in selected patients aged 60 years and older results in survival comparable with that of younger patients. Older patients have a lower risk of rejection but an increased risk of development of a nonposttransplant lymphoproliferative disorder cancer. Advanced age per se should not be considered as an exclusion criterion for transplantation.

    View details for DOI 10.1016/S0022-5223(03)00055-2

    View details for Web of Science ID 000184365400028

    View details for PubMedID 12878959

  • Simplified technique for correction of anomalous origin of left coronary artery from the anterior aortic sinus ANNALS OF THORACIC SURGERY Karamichalis, J. M., Vricella, L. A., Murphy, D. J., Reitz, B. A. 2003; 76 (1): 266-267

    Abstract

    Anomalous origin of the left main coronary artery from the right anterior coronary sinus has been associated with high incidence of sudden death in young adults. We describe a simplified approach to this rare congenital anomaly, which avoids the need for commissural post resuspension or relocation of the coronary button.

    View details for Web of Science ID 000183968400059

    View details for PubMedID 12842554

  • Surgical correction of tetralogy of Fallot in adults in the current era 52nd Annual Scientific Session of the American-College-of-Cardiology Cheng, C. W., Feinstein, J. A., Reitz, B., Murphy, D. J. ELSEVIER SCIENCE INC. 2003: 479A–479A
  • Bridge to heart transplantation: A comparison of LVAD and inotropic support American-Heart-Association Abstracts From Scientific Sessions Moffatt, S., Demers, P., Chan, M., Oyer, P., Reitz, B. A., Robbins, R. LIPPINCOTT WILLIAMS & WILKINS. 2002: 419–19
  • Is medical therapy still the optimal treatment strategy for patients with acute type B aortic dissections? 27th Annual Meeting of the Western-Thoracic-Surgical-Association Umana, J. P., Lai, D. T., Mitchell, R. S., Moore, K. A., Rodriguez, F., Robbins, R. C., Oyer, P. E., Dake, M. D., Shumway, N. E., Reitz, B. A., Miller, D. C. MOSBY-ELSEVIER. 2002: 896–910

    Abstract

    The optimal treatment of patients with acute type B dissections continues to be debated.A 36-year clinical experience of medical and surgical treatments in 189 patients was retrospectively analyzed (multivariable Cox proportional hazards model) with respect to three outcome end points: all deaths, freedom from reoperation, and freedom from late aortic complications or death. Propensity score analysis identified 2 quintiles (quintiles I and II, consisting of 142 comparable patients) for further comparison of the effects of surgical versus medical treatment.Shock (hazard ratio 14.5, 95% confidence interval 4.7-44.5, P <.001) and visceral ischemia (hazard ratio 10.9, 95% confidence interval 3.9-30.3, P <.001) largely predominated as determinants of death, along with 6 other risk factors (arch involvement, rupture, stroke, previous sternotomy, and coronary or lung disease), which roughly doubled the hazard of death. Female sex was a significant but weaker predictor of death. Renal dysfunction, year of presentation, age, and mode of therapy (medical vs surgical) had no important bearing on overall survival. The actuarial survival estimates for all patients were 71%, 60%, 35%, and 17% at 1, 5, 10, and 15 years, respectively, and were similar for the medical and surgical patients. Reoperation and late aortic complications were predicted by the presence of Marfan syndrome. For the propensity-matched patients in quintiles I and II, survival, freedom from reoperation, and freedom from aortic complications were almost identical in the medically treated and surgical subsets.The prognosis for patients with acute type B aortic dissection is bleak and determined primarily by dissection-related and patient-specific risk factors, which do not appear to be readily modifiable.

    View details for DOI 10.1067/mtc.2002.123131

    View details for Web of Science ID 000179012300006

    View details for PubMedID 12407372

  • Does profound hypothermic circulatory arrest improve survival in patients with acute type a aortic dissection? Circulation Lai, D. T., Robbins, R. C., Mitchell, R. S., Moore, K. A., Oyer, P. E., Shumway, N. E., Reitz, B. A., Miller, D. C. 2002; 106 (12): I218-28

    Abstract

    No evidence exists that profound hypothermic circulatory arrest (PHCA) improves survival or reduces the likelihood of distal aortic reoperation in patients with acute type A aortic dissection.Records of 307 patients with acute type A aortic dissection from 1967 to 1999 were retrospectively reviewed. The influence of repair using PHCA (n=121) versus without PHCA (n=186) on death and freedom from distal aortic reoperation was analyzed using multivariable Cox regression models. Propensity score analysis identified a subset of 152 comparable patients in 3 quintiles (QIII-V) in which the effects of PHCA (n=113) versus no PHCA (n=39) were further compared.For all patients, 30-day, 1-year, and 5-year survival estimates were 81+/-2%, 74+/-3%, and 63+/-3% (+/-1 SE). Survival rates and actual freedom from distal aortic reoperation was not significantly different between treatment methods in the entire patient cohort nor in the matched patients in quintiles III-V. Treatment method was not associated with differences in early major complications, late survival, or distal aortic reoperation rates in the entire patient sample or in quintiles III-V.Aortic repair with or without circulatory arrest was associated with comparable early complications, survival, and distal aortic reoperation rates in patients with acute type A aortic dissection. Despite the lack of concrete evidence favoring the use of PHCA, it does no harm, and most of our group uses PHCA regularly because of its practical technical advantages and theoretical potential merit.

    View details for PubMedID 12354737

  • Does profound hypothermic circulatory arrest improve survival in patients with acute type a aortic dissection? CIRCULATION Lai, D. T., Robbins, R. C., Mitchell, R. S., Moore, K. A., Oyer, P. E., Shumway, N. E., Reitz, B. A., Miller, D. C. 2002; 106 (13): I218-I228

    Abstract

    No evidence exists that profound hypothermic circulatory arrest (PHCA) improves survival or reduces the likelihood of distal aortic reoperation in patients with acute type A aortic dissection.Records of 307 patients with acute type A aortic dissection from 1967 to 1999 were retrospectively reviewed. The influence of repair using PHCA (n=121) versus without PHCA (n=186) on death and freedom from distal aortic reoperation was analyzed using multivariable Cox regression models. Propensity score analysis identified a subset of 152 comparable patients in 3 quintiles (QIII-V) in which the effects of PHCA (n=113) versus no PHCA (n=39) were further compared.For all patients, 30-day, 1-year, and 5-year survival estimates were 81+/-2%, 74+/-3%, and 63+/-3% (+/-1 SE). Survival rates and actual freedom from distal aortic reoperation was not significantly different between treatment methods in the entire patient cohort nor in the matched patients in quintiles III-V. Treatment method was not associated with differences in early major complications, late survival, or distal aortic reoperation rates in the entire patient sample or in quintiles III-V.Aortic repair with or without circulatory arrest was associated with comparable early complications, survival, and distal aortic reoperation rates in patients with acute type A aortic dissection. Despite the lack of concrete evidence favoring the use of PHCA, it does no harm, and most of our group uses PHCA regularly because of its practical technical advantages and theoretical potential merit.

    View details for DOI 10.1161/01.cir.000032890.55215.27

    View details for Web of Science ID 000178318900039

  • What cardiothoracic surgeons in the 21st century should be? Kyobu geka. The Japanese journal of thoracic surgery Reitz, B. A. 2002; 55 (8): 710-714

    View details for PubMedID 12174663

  • Long-term follow-up after total lymphoid irradiation in pediatric heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Chin, C., Hunt, S., Robbins, R., Hoppe, R., Reitz, B., Bernstein, D. 2002; 21 (6): 667-673

    Abstract

    Total lymphoid irradiation (TLI) is used to treat recurrent allograft rejection. Short-term success and complication rates have been reported in pediatric and adult cardiac transplant populations. We report the long-term efficacy and safety of TLI in treating intractable rejection in pediatric patients.Eight pediatric patients were treated with TLI (7 for recurrent rejection, 1 for risk of medication non-compliance). Therapy consisted of a mid-plane dose of 8 Gy administered with a 6-MeV linear accelerator using an anterior-posterior opposed technique. We reviewed outcomes for a total of 40 patient-years of follow-up.We encountered rejection (>Grade 2 by International Society for Heart and Lung Transplantation criteria) in 56.7% +/- 34.7% of biopsies performed within 90 days before TLI. Rejection rates dropped to 3.1% +/- 8.8% within the first 90 days (p < 0.005) after therapy and remained low at 5.6% +/- 1.3% (p < 0.05) during the first year after completion of TLI. Median time from TLI to the first subsequent rejection episode was 305 days (range, 77-1,920 days). Long-term follow-up (>3 years) of 5 patients demonstrated a continuing low incidence of rejection. Non-Hodgkin's lymphoma was diagnosed in 1 of 8 patients, graft coronary artery disease in 4 of 8 patients, and restrictive cardiomyopathy in 1 of 8 patients after TLI.Total lymphoid irradiation is an effective treatment for recurrent rejection and has short- and long-term efficacy. Morbid events may include cancer, graft coronary artery disease, and restrictive cardiomyopathy.

    View details for Web of Science ID 000176074500008

    View details for PubMedID 12057700

  • Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation - A comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone TRANSPLANTATION Valantine, H. A., Luikart, H., Doyle, R., Theodore, J., Hunt, S., Oyer, P., Robbins, R., Berry, G., Reitz, B. 2001; 72 (10): 1647-1652

    Abstract

    Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclovir compared with placebo in seronegative recipients of hearts from seropositive donors (D+/R-). This study tests the hypothesis that a combination of ganciclovir plus CMV hyperimmune globulin (CMVIG) is more effective than ganciclovir alone for preventing acute CMV illness and its long-term sequelae.The study population receiving CMVIG (n=80) included 27 heart transplant recipients (D+/R-) and 53 heart-lung and lung transplant recipients (R+ and/or D+). Each group was matched with historical controls who underwent transplantation within the preceding 2-3 years. Outcome measures compared were as follows: 3-year incidence of CMV disease; fungal infection; acute rejection; survival; rates and severity of transplant coronary artery disease (in heart patients) defined by intimal thickness (ultrasound) and coronary artery stenosis (angiographic); and incidence and death from obliterative bronchiolitis defined by pathological criteria on endobronchial biopsy specimens (in heart-lung/lung patients).Patients treated with CMVIG had a higher disease-free incidence of CMV, lower rejection incidence, and higher survival rate compared with the patients treated with ganciclovir alone. The coronary artery intimal thickness and the prevalence of intimal thickening were lower in the patients receiving CMVIG. Heart-lung and lung transplant patients treated with CMVIG had lower incidences of obliterative bronchiolitis and death from obliterative bronchiolitis and longer survival compared with the patients treated with ganciclovir alone.CMVIG plus ganciclovir seems to be more effective that ganciclovir alone for preventing the sequelae of CMV infection. A prospective randomized study is required to confirm these observations.

    View details for Web of Science ID 000172614200012

    View details for PubMedID 11726825

  • Does hypothermic circulatory arrest (PHCA) improve survival in patients with acute type A aortic dissection? Lai, D. T., Robbins, R. C., Mitchell, R. S., Moore, K. A., Oyer, P. E., Shumway, N. E., Reitz, B. A., Miller, D. C. LIPPINCOTT WILLIAMS & WILKINS. 2001: 524–24
  • Treatment of endocarditis with valve replacement: The question of tissue versus mechanical prosthesis ANNALS OF THORACIC SURGERY Moon, M. R., Miller, D. C., Moore, K. A., Oyer, P. E., Mitchell, R. S., Robbins, R. C., Stinson, E. B., Shumway, N. E., Reitz, B. A. 2001; 71 (4): 1164-1171

    Abstract

    It remains unknown whether there is any important clinical advantage to the use of either a bioprosthetic or mechanical valve for patients with native or prosthetic valve endocarditis.Between 1964 and 1995, 306 patients underwent valve replacement for left-sided native (209 patients) or prosthetic (97 patients) valve endocarditis. Mechanical valves were implanted in 65 patients, bioprostheses in 221 patients, and homografts in 20 patients.Operative mortality was 18+/-2% and was independent of replacement valve type (p > 0.74). Long-term survival was superior for patients with native valve endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve type (p > 0.27). The long-term freedom from reoperation for patients who received a biologic valve who were younger than 60 years of age was low (51+/-5% at 10 years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom from reoperation with a biological valve (84+/-7% at 15 years) was similar to that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64).Mechanical valves are most suitable for younger patients with native valve endocarditis; however, tissue valves are acceptable for patients greater than 60 years of age with native or prosthetic valve infections and for selected younger patients with prosthetic valve infections because of their limited life expectancy.

    View details for Web of Science ID 000168590600017

    View details for PubMedID 11308154

  • A report of two hundred twenty cases of regional anesthesia in pediatric cardiac surgery ANESTHESIA AND ANALGESIA Peterson, K. L., DeCampli, W. M., Pike, N. A., Robbins, R. C., Reitz, B. A. 2000; 90 (5): 1014-1019

    Abstract

    The use of regional anesthesia (ie, epidural, spinal, or caudal) has been reported in a few small series of children undergoing cardiac surgery, but not in larger studies. In this retrospective, descriptive study, we report the results of the use of regional anesthesia in 220 pediatric cardiac operations. We reviewed the records of children receiving a regional anesthetic for cardiothoracic surgery at Stanford Medical Center between January 1993 and February 1997. All patients were targeted for early tracheal extubation. A variety of regional techniques were used. Time to extubation, control of pain, incidence of respiratory depression and other complications, and length of hospital stay were determined. There were no deaths. Eighty-nine percent of the patients were tracheally extubated in the operating room; 4.1% of whom required reintubation within 24 h. Ninety-five percent +/-2.5% of the patients had pain scores < or =4.0 at all intervals postoperatively. Adverse effects of regional anesthesia included emesis (39%), pruritus (10%), urinary retention (7%), postoperative transient paresthesia (3%), and respiratory depression (1.8%). The incidence of peridural hematoma was zero. The rate of adverse effects was lower in the thoracic catheter epidural approach as compared with various caudal, lumbar epidural, and spinal approaches. Hospital duration of stay was not effected by the presence of regional anesthetic complications. In this study, regional anesthesia was safe and effective in the management of pediatric patients undergoing cardiac surgery.

    View details for Web of Science ID 000086764200002

    View details for PubMedID 10781445

  • Heart-lung versus double-lung transplantation for suppurative lung disease 78th Annual Meeting of the American-Association-for-Thoracic-Surgery Barlow, C. W., Robbins, R. C., Moon, M. R., Akindipe, O., Theodore, J., Reitz, B. A. MOSBY-ELSEVIER. 2000: 466–75

    Abstract

    The purpose of this study was to compare outcomes after heart-lung or double-lung transplantation in patients undergoing transplantation because of end-stage suppurative lung disease.We reviewed our experience in patients with cystic fibrosis or bronchiectasis who had heart-lung or double-lung transplantation between January 1988 and September 1997. Twenty-three patients (14 male, 21 cystic fibrosis) had heart-lung transplantation and 24 patients (8 male, 19 cystic fibrosis) had double-lung transplantation. There were no statistically significant differences between the groups in age, weight, preoperative creatinine level, cytomegalovirus status, maintenance immunosuppression, or donor demographics. Patients received induction therapy with monoclonal (OKT3) or polyclonal (rabbit anti-thymocyte globulin) antibody.Sixteen of 24 patients had double-lung transplantation after 1994 whereas 13 of 22 patients had heart-lung transplantation before 1991, allowing longer follow-up for the heart-lung group. Mean waiting times for transplantation were 270 +/- 245 days (heart-lung) and 361 +/- 229 days (double-lung; P =.20). The 1-, 3-, and 5-year actuarial survival figures were respectively 86%, 82%, and 65% (heart-lung) and 96%, 75%, and unavailable (double-lung; P = no significant difference). The 1-, 3-, and 5-year rates of freedom from obliterative bronchiolitis were respectively 77%, 61%, and 45% (heart-lung) and 86%, 78%, and unavailable (double-lung; P = no significant difference). Linearized overall infection rates (events/100 patient-days) were 2.05 +/- 0.33 (heart-lung) and 2.34 +/- 0.34 (double-lung; P = NS) at 3 months. Thirty-day survival was 100% (heart-lung) and 96% (double-lung). There were 7 late deaths among heart-lung recipients (3 obliterative bronchiolitis, 2 infection, 0 graft coronary artery disease, 2 other) whereas 2 late deaths related to obliterative bronchiolitis occurred in double-lung recipients. Graft coronary artery disease (all stenoses < 50%) affected 15% of heart-lung survivors, whereas 3 double-lung recipients (12.5%) required either bronchial dilatation or stenting.Heart-lung and double-lung transplantation provide similar palliation for patients with end-stage suppurative lung disease. Therefore double-lung transplantation should be the preferred operation for most patients with end-stage suppurative lung disease.

    View details for Web of Science ID 000085766600015

    View details for PubMedID 10694605

  • The use of advanced-age donor hearts adversely affects survival in pediatric heart transplantation. Pediatric transplantation Chin, C., Miller, J., Robbins, R., Reitz, B., Bernstein, D. 1999; 3 (4): 309-314

    Abstract

    There is a limited supply of adequate donor hearts for cardiac transplantation. The safety of using advanced-age donor hearts has been debated in adult transplantation but has not been studied previously in pediatric recipients. In this retrospective study, survival of 79 pediatric heart transplant recipients was reviewed. Pediatric recipient groups were stratified based on donor age (group 1 donor age > 40 yr, n = 5; group 2 donor age < or = 40 yr, n = 74). Survival of 267 adolescent (ages 11-17) heart transplant recipients in the United Network for Organ Sharing (UNOS) database was also reviewed. Patients were likewise divided into two groups based on donor age (> 40 yr, n = 12; < or = 40 yr, n = 255). Survival at one yr was 20% in group 1 vs. 78% in group 2 (p < 0.005). Cause of death in all group 1 patients was graft failure secondary to acute rejection. Analysis of risk of death was only significantly attributable to the age of the donor. The increased risk attributable to advanced donor age was also supported by the UNOS data. The UNOS one and two-year Kaplan-Meier survival curves were significantly lower in adolescent patients who received donor hearts > 40 yr of age. One-year survival was 58% (older donors) vs. 85% (younger donors, p < 0.005) and two-year survival was 44% (older donors) vs. 79% (younger donors, p < 0.005). Advanced-age donor hearts should be contraindicated in pediatric transplantation with the exception of critically ill patients who may not be able to wait for a younger heart.

    View details for PubMedID 10562976

  • Heart-lung transplantation for primary pulmonary hypertension 34th Annual Meeting of the Society-of-Thoracic-Surgeons Whyte, R. I., Robbins, R. C., Altinger, J., Barlow, C. W., Doyle, R., Theodore, J., Reitz, B. A. ELSEVIER SCIENCE INC. 1999: 937–41

    Abstract

    The operation of choice for primary pulmonary hypertension remains controversial, as heart-lung transplantation, single-lung transplantation, and double-lung transplantation have all been advocated.We reviewed our institution's experience with heart-lung transplantation for primary pulmonary hypertension.Thirty-nine patients had heart-lung transplantation for primary pulmonary hypertension. Operative mortality rate was 18%, and actuarial survival was 72% at 1 year, 67% at 2 years, and 42% at 5 years. Freedom from obliterative bronchiolitis was 91% at 1 year, 83% at 2 years, and 70% at 5 years. Freedom from obliterative bronchiolitis-related death was 100% at 1 year, 90% at 2 years, and 87% at 5 years. Freedom from accelerated graft coronary disease was 92% at 5 years. The most frequent causes of death were infection, obliterative bronchiolitis, and accelerated graft coronary disease.Heart-lung transplantation results in survival comparable to that reported for single or double lung transplantation. Obliterative bronchiolitis is a significant cause of late death but seems to occur less frequently with heart-lung transplantation than with lung transplantation alone. Accelerated coronary graft disease is rare in the first 5 years after transplantation.

    View details for Web of Science ID 000080115300010

    View details for PubMedID 10320232

  • Effect of low molecular weight heparin on graft vascular disease in the rat cardiac allograft model XVIIth World Congress of the Transplantation-Society Teranishi, K., Poston, R. S., Reitz, B. A., Robbins, R. C. ELSEVIER SCIENCE INC. 1999: 103–5

    View details for Web of Science ID 000078960600039

    View details for PubMedID 10083030

  • First report of the Port Access International Registry 34th Annual Meeting of the Society-of-Thoracic-Surgeons Galloway, A. C., Shemin, R. J., Glower, D. D., Boyer, J. H., Groh, M. A., Kuntz, R. E., Burdon, T. A., Ribakove, G. H., Reitz, B. A., Colvin, S. B. ELSEVIER SCIENCE INC. 1999: 51–56

    Abstract

    For minimally invasive cardiac operations to be widely applicable, the risks must be equivalent to those of standard open-chest operations. This study analyzed the outcomes of patients recorded in the multicenter Port Access (PA) International Registry to establish operative risks.Data were analyzed for intent to treat in 583 patients who underwent PA coronary artery bypass grafting (CABG), 184 who underwent PA mitral valve replacement, and 137 who underwent PA mitral valve repair at 121 centers.Port Access was attempted in 1,063 patients and completed in 1,004 (94%). The operative mortality rate was 1% for PA CABG, 3.3% for PA mitral valve replacement, and 1.5% for PA mitral valve repair. Perioperative morbidity was low in all categories: stroke = 1.1% to 3.6%, myocardial infarction = 0 to 1%, primary procedure reoperation = 0 to 0.7%, renal failure = 0.2% to 0.7%, multiorgan failure = 0 to 0.5%, and atrial fibrillation = 5% to 7.3%.Data on 1,063 patients from 121 centers demonstrate that PA CABG and PA mitral valve operations can be performed safely, with morbidity and mortality rates similar to those associated with open-chest operations. Further studies are indicated to establish the long-term efficacy of this method and to analyze its effect on recovery time.

    View details for Web of Science ID 000078970500008

    View details for PubMedID 10086524

  • The future of minimally invasive myocardial revascularization: A surgeon's view JOURNAL OF CARDIAC SURGERY Stevens, J. H., Reitz, B. A. 1998; 13 (4): 266-267

    View details for Web of Science ID 000081808900008

    View details for PubMedID 10225182

  • Effect of low molecular weight heparin on suppression of chronic graft vascular disease in a rat cardiac allograft model International Congress on Immunosuppression Teranishi, K., Poston, R. S., Reitz, B. A., Robbins, R. C. ELSEVIER SCIENCE INC. 1998: 1009–11

    View details for Web of Science ID 000074150800033

    View details for PubMedID 9636408

  • Effect of cyclosporine on chronic graft vascular disease in a rat cardiac isograft model International Congress on Immunosuppression Teranishi, K., Poston, R. S., Tsao, P. S., Asagami, T., Cooke, J. P., Reitz, B. A., Robbins, R. C. ELSEVIER SCIENCE INC. 1998: 1012–13

    View details for Web of Science ID 000074150800034

    View details for PubMedID 9636409

  • Oral delivery of low molecular weight heparin in rat cardiac allografts International Congress on Immunosuppression Teranishi, K., Poston, R. S., Reitz, B. A., Robbins, R. C. ELSEVIER SCIENCE INC. 1998: 996–97

    View details for Web of Science ID 000074150800027

    View details for PubMedID 9636402

  • Combined heart and single-lung transplantation in complex congenital heart disease ANNALS OF THORACIC SURGERY Fann, J. I., Wilson, M. K., Theodore, J., Reitz, B. A. 1998; 65 (3): 823-825

    Abstract

    We present a patient with a history of tricuspid and pulmonary atresia who underwent a classic Glenn shunt and a Potts shunt during childhood, resulting in different right and left pulmonary physiology. Because of progression of cardiopulmonary disease and the fact that the right lung was "protected," the patient underwent combined heart-left single-lung transplantation. The postoperative course was uneventful. Potential early and late advantages of this approach include simplifying of the operative procedure and mitigating the potential effects of obliterative bronchiolitis.

    View details for Web of Science ID 000072586100048

    View details for PubMedID 9527222

  • Arrhythmias and thromboembolic complications after the extracardiac Fontan operation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shirai, L. K., Rosenthal, D. N., Reitz, B. A., Robbins, R. C., Dubin, A. M. 1998; 115 (3): 499-505

    Abstract

    Late morbidity and mortality after the Fontan operation are largely due to atrial arrhythmias, ventricular failure, and thrombus formation. The extracardiac Fontan procedure avoids extensive atrial manipulation and suture lines, theoretically minimizing the impetus for these events. We examined our experience with the extracardiac Fontan operation with particular attention to thromboembolism and arrhythmias.We retrospectively reviewed the medical and surgical records of all 16 patients who underwent an extracardiac Fontan operation between July 1993 and May 1996. Fifteen patients (94%) were in sinus rhythm before the operation. In the immediate postoperative period, seven (44%) had arrhythmias consisting of accelerated junctional rhythm and ectopic atrial rhythm. No associated hemodynamic compromise and no early deaths occurred. Patients were followed up for 3 to 34 months after the Fontan operation. Arrhythmias were detected in eight patients (50%) on surface electrocardiograms, and seven (44%) showed evidence of sinus node dysfunction on 24-hour Holter monitor studies. Thrombi were found in three patients (19%). All patients were asymptomatic, with no evidence of conduit obstruction by echocardiogram.The incidence of hemodynamically significant tachyarrhythmias appears to be reduced after the extracardiac Fontan operation. A significant percentage of patients have evidence of sinus node dysfunction, suggesting the presence of other surgical or nonsurgical factors responsible for this finding. Our incidence of thrombotic events is similar to previous reports with other Fontan modifications. It appears to be a reasonable option to maintain these patients on anticoagulation indefinitely.

    View details for Web of Science ID 000072718800002

    View details for PubMedID 9535435

  • Composite valve graft versus separate aortic valve and ascending aortic replacement: is there still a role for the separate procedure? Circulation Yun, K. L., Miller, D. C., Fann, J. I., Mitchell, R. S., Robbins, R. C., Moore, K. A., Oyer, P. E., Stinson, E. B., Shumway, N. E., Reitz, B. A. 1997; 96 (9): II-368 75

    Abstract

    To ascertain if operative technique has any bearing on outcome, the surgical results after aortic root replacement using either a composite valve graft (CVG) or a separate graft and valve (GV) were analyzed.Three hundred and ninety consecutive, nonrandomized patients treated for aortic valve disease and ascending aortic aneurysm (n=278) or type A dissection (n=112 [45 acute]) between 1965 and 1995 were analyzed retrospectively. One hundred and thirty-five patients received a CVG, and 255 had separate GV replacement. Mean age was 52+/-16 years (+/-1 SD). Eighty-two patients (44% of the CVG group) had the Marfan syndrome (MFS). Follow-up (96% complete) totaled 2247 patient-years and extended to 27 years. The operative mortality rate was 10+/-3% (+/-70% confidence limits) for patients receiving a CVG and 15+/-2% for GV replacement (P=NS). The 15-year actuarial survival estimate was higher for the CVG group (53+/-14% [+/-SEM] versus 36+/-4%, P=.037). Seven patients in the CVG group required reoperation on the aortic valve or ascending aorta, as did 49 in the GV group. The probabilities of freedom from reoperation on the aortic rootwere 82+/-9% and 75+/-4% at 10 years for the CVG and GV group (P=NS). Thirty variables were analyzed in a multivariate model: pulmonary disease, higher New York Heart Association functional class, and longer cardiopulmonary bypass time were linked with higher operative mortality risk; older age, emergency operation, coronary artery disease, and liver dysfunction were independent determinants of late death. Younger age and use of a bioprosthesis were predictors of late reoperation. Type of procedure (GV versus CVG) was not a significant predictor of any outcome variable.The long-term results after CVG or GV were similar, which reflects proper patient selection. Use of a composite valve graft theoretically confers more protection against recurrent aortic root aneurysm, and, unless one opts for a valve-sparing aortic root replacement procedure, is most appropriate for younger patients, those with the MFS (including acute dissections), and others with marked pathological involvement of the sinuses. On the other hand, use of a separate GV should not be abandoned; in carefully selected patients (and if properly performed, eg, excision of the sinuses), GV also provides satisfactory results.

    View details for PubMedID 9386126

  • Composite valve graft versus separate aortic valve and ascending aortic replacement - Is there still a role for the separate procedure? 69th Annual Scientific Session of the American-Heart-Association Yun, K. L., Miller, D. C., Fann, J. I., Mitchell, S., Robbins, R. C., Moore, K. A., Oyer, P. E., Stinson, E. B., Shumway, N. E., Reitz, B. A. LIPPINCOTT WILLIAMS & WILKINS. 1997: 368–75
  • Surgical treatment of endocarditis: Is there a role for mechanical prostheses? Moon, M. R., Miller, D. C., Stinson, E. B., Mitchell, R. S., Oyer, P. E., Robbins, R. C., Shumway, N. E., Reitz, B. A. LIPPINCOTT WILLIAMS & WILKINS. 1997: 2409–
  • CMV hyperimmune globulin and ganciclovir is more effective than ganciclovir alone for CMV prophylaxis after cardiothoracic transplantation. vonKaeppler, H. A., Poirier, C. D., Doyle, R., Theodore, J., Woodley, S., Luikart, H., Hunt, S. A., Stinson, E. B., Reitz, B. A. LIPPINCOTT WILLIAMS & WILKINS. 1997: 350–50
  • Obliterative airway disease after heterotopic tracheal xenotransplantation: Pathogenesis and prevention using new immunosuppressive agents TRANSPLANTATION Reichenspurner, H., Soni, V., Nitschke, M., Berry, G. J., Brazelton, T. R., Shorthouse, R., Huang, X. F., Reitz, B. A., Morris, R. E. 1997; 64 (3): 373-383

    Abstract

    The purpose of this study was to investigate whether obliterative bronchiolitis might occur after xenogenic pulmonary transplantation. A model for obliterative airway disease (OAD) after tracheal allograft transplantation in the rat undergoes tracheal obliteration with histologic features characteristic of obliterative bronchiolitis in human lung transplant recipients. Using this model, the pathogenesis of OAD and its prevention with immunosuppressive drugs was studied in rat recipients of hamster tracheal grafts.Tracheae from 30 hamsters (xenografts) or 23 Brown-Norway rats (allografts) were implanted and wrapped in the greater omentum of untreated Lewis rats. The grafts were removed on day 1, 3, 7, 14, 21, or 28 after transplantation and stained with hematoxylin and eosin and Masson's trichrome and by immunohistochemistry and immunofluorescence (IFL) techniques. In addition, 25 recipients were treated with cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin (RPM, 6 mg/kg i.p.) for 14 or 21 days (5 animals per treatment group). Visual and morphometric analyses were used to evaluate the extent of airway obliteration, luminal coverage by respiratory or flattened cuboidal epithelium, and extent and density of peritracheal cellular inflammation.In all xenografts, a neutrophilic infiltration of the mucosa and submucosa was observed from day 1 until day 14 and was associated with complete loss of tracheal epithelium by day 14. A marked peritracheal mononuclear cellular infiltrate mixed with plasma cells and eosinophils was seen on days 7 and 14. Both the extent of peritracheal inflammation and the density of the mononuclear cell infiltrate were significantly increased in xenograft tracheae when compared with the allografts. Tracheal obliteration began on day 14 and reached a maximum of 43% on day 21 with evidence of intraluminal fibrosis. In contrast to IFL of allografts, IFL of xenografts demonstrated marked deposition of rat immunoglobulin in the peritracheal tissue on days 7 and 14. The effects of treatment with immunosuppressive drugs on tracheal graft narrowing and protection of respiratory epithelium were as follows: After 14 days of treatment, the percentage of tracheal graft narrowing was 12%, 23%, and 19% in the no treatment, CsA, and LFM groups, respectively; the percentage of respiratory epithelium at 14 days was 0%, 21%, and 95%. After 21 days of treatment, the percentage of tracheal graft narrowing was 43%, 49%, 12%, and 5% for the no treatment, CsA, LFM, and RPM groups, respectively; the percentage of respiratory epithelium at 21 days was 0%, 39%, 86%, and 0%. Using computerized morphometry, the extent and densities of the peritracheal cellular infiltrates were significantly reduced in LFM- and CsA-treated groups when compared with untreated xenograft controls. LFM and RPM, but not CsA, significantly reduced the degree of luminal obliteration compared with no treatment (P<0.05). LFM and, to a lesser extent, CsA were able to prevent the loss of normal respiratory epithelium. Analysis by IFL revealed a marked decrease in rat immunoglobulin deposition in xenografts from LFM- and RPM-treated groups compared with xenografts from CsA-treated or untreated rats.(1) OAD occurs not only after tracheal allotransplantation but also after xenotransplantation. (2) Subepithelial infiltration of neutrophils and the appearance of plasma cells and eosinophils in the peritracheal infiltrates distinguished the histology of rejected xenografts from allografts. (3) Antibody deposition was detected by IFL only in xenografts. (4) Treatment with LFM or RPM significantly decreased the severity of luminal obliteration. Importantly, LFM also prevented the loss of respiratory epithelium.

    View details for Web of Science ID A1997XR62400001

    View details for PubMedID 9275099

  • Monitoring considerations for port-access cardiac surgery CIRCULATION Siegel, L. C., STGOAR, F. G., Stevens, J. H., Pompili, M. F., Burdon, T. A., Reitz, B. A., Peters, W. S. 1997; 96 (2): 562-568

    Abstract

    A method for monitoring patients was evaluated in a clinical trial of minimally invasive port-access cardiac surgery with closed chest endovascular cardiopulmonary bypass.Cardiopulmonary bypass was conducted in 25 patients through femoral cannulas. An endovascular pulmonary artery vent was placed in the main pulmonary artery through a jugular vein. For mitral valve surgery, a catheter was placed in the coronary sinus for delivery of cardioplegia. A balloon catheter ("endoaortic clamp," EAC) used for occlusion of the ascending aorta, delivery of cardioplegia, aortic root venting, and pressure measurement was inserted through a femoral artery and initially positioned by use of fluoroscopy and transesophageal echocardiography (TEE). Potential migration of the EAC was monitored by (1) TEE of the ascending aorta, (2) pulsed-wave Doppler of the right carotid artery, (3) balloon pressure, (4) comparison of aortic root pressure and right radial artery pressure, and (5) fluoroscopy. TEE, fluoroscopy, and pressure measurement were effective in monitoring catheter insertion and position. With inadequate balloon inflation, migration of the EAC toward the aortic valve could be detected with TEE. During administration of cardioplegia, TEE showed movement of the balloon away from the aortic valve, and migration into the aortic arch was detectable with loss of carotid Doppler flow. Stability of EAC position was demonstrated with appropriate balloon volume. Cardioplegic solution was visualized in the aortic root, and aortic root pressure changed appropriately during administration of cardioplegia. Venous cannula position was optimized with TEE and endopulmonary vent flow measurement.An effective method has been developed for monitoring patients and the catheter system during port-access cardiac surgery.

    View details for Web of Science ID A1997XM00300034

    View details for PubMedID 9244226

  • Perinatal induction of immunotolerance to cardiac and pulmonary allografts JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yuh, D. D., Gandy, K. L., Reitz, B. A., Hoyt, G., Robbins, R. C. 1997; 114 (1): 64-75

    Abstract

    Tolerance appears to be more easily induced in the fetus before full immunocompetence is established, but elucidation of this process is needed. A model of perinatal tolerance induction to neonatal skin allografts followed by cardiac and pulmonary allografts is described.Sixty Lewis (RT11) rat fetuses were inoculated intraperitoneally at 18 days gestation with 1 x 10(7) ACI (RT1a) rat fetal liver cells (group I); 20 Lewis fetuses were inoculated with 2 x 10(7) ACI fetal liver cells (Group II). control groups consisted of Lewis fetuses inoculated with saline solution (n = 25, group III) and fetuses that were not inoculated (n = 25, group IV). Twenty-five of the 50 surviving group I rats received ACI skin (< 24 hours old) and heart (8 to 10 weeks old) allografts (group IA); the remaining 25 rats received only ACI heart grafts (group IB). Groups II, III, and IV received ACI skin and cardiac allografts. Recipients tolerant to both skin and cardiac grafts received orthotopic ACI lung grafts and third-party skin grafts. Tolerance was indicated by graft survival for more than 100 days. Limiting dilution and flow cytometric analyses were performed.Abortion rates in groups I, II, III, and IV were 17% (10/60), 65% (13/20), 8% (2/25), and 4% (1/25), respectively. Specific tolerance to skin, cardiac, and lung allografts was observed in seven of 25 group IA recipients (28%) and seven of seven group II recipients (100%) compared with no tolerance in any group IB, III, or IV recipients (p = 0.03, chi 2 test). A 100-fold reduction of precursor cytotoxic T lymphocytes and significant splenocyte and bone marrow chimerism in tolerant versus nontolerant rats were noted (p = 0.0001, Student's t test).Using donor-strain fetal liver cells and neonatal skin grafts, we achieved higher frequencies of tolerance to solid organ grafts in adulthood with lower cell inocula and abortion rates than previously described. Chimerism and depressed precursor cytotoxic T lymphocyte frequencies in tolerant recipients suggest that hematopoietic stem cell engraftment and clonal deletion/anergy are involved in induction of perinatal tolerance.

    View details for Web of Science ID A1997XM02300010

    View details for PubMedID 9240295

  • Perfusion during coronary and mitral valve surgery utilizing minimally invasive Port-Access technology. The Journal of extra-corporeal technology Toomasian, J. M., Williams, D. L., Colvin, S. B., Reitz, B. A. 1997; 29 (2): 66-72

    Abstract

    Minimally invasive surgery has been used in the treatment of some cardiovascular diseases. Port-Access surgery is a new minimally invasive technique that utilizes cardiopulmonary by-pass and a specialized catheter system that provides cardiopulmonary support and myocardial preservation. Extrathoracic cardiopulmonary support is established with femero-femoral bypass with kinetic assisted venous drainage. An endovascular catheter system allows for all the benefits of mechanical support as well as myocardial preservation. This catheter system includes an endoaortic balloon catheter which functions as an aortic cross clamp and antegrade cardioplegia delivery catheter, endopulmonary vent, and endocoronary sinus catheter used for administration of retrograde cardioplegia. An initial cohort of 20 patients was treated by the Port-Access surgical approach with cardiopulmonary bypass. Ten patients had coronary artery surgery and 10 patients had mitral valve surgery. The average bypass times were 94.4 min (coronary artery) and 152.8 min (mitral valve). The mean aortic occlusion times were 49.7 min (coronary artery) and 112.6 min (mitral valve). All patients were weaned from bypass. This initial patient series demonstrated that Port-Access surgery was feasible in selected patients.

    View details for PubMedID 10173052

  • Long-term survivors of pediatric heart transplantation: A multicenter report of sixty-eight children who have survived longer than five years JOURNAL OF PEDIATRICS Sigfusson, G., Fricker, F. J., Bernstein, D., Addonizio, L. J., Baum, D., Hsu, D. T., Chin, C., Miller, S. A., Boyle, G. J., Miller, J., Lawrence, K. S., DOUGLAS, J. F., Griffith, B. P., Reitz, B. A., Michler, R. E., Rose, E. A., Webber, S. A. 1997; 130 (6): 862-871

    Abstract

    Short-term survival after pediatric heart transplantation is now excellent, but ultimately the efficacy of this procedure will depend on duration and quality of survival. We sought to evaluate the clinical course of long-term survivors of heart transplantation in childhood.Patients who had undergone heart transplantation at the university hospitals of Stanford, Columbia, and Pittsburgh between 1975 and 1989 and survived longer than 5 years from transplantation were identified and their clinical courses retrospectively reviewed.Sixty eight children have survived more than 5 years from transplantation, and 60 (88%) are currently alive with a median follow-up of 6.8 years (5 to 17.9 years). Thirteen have survived more than 10 years from transplantation. Renal dysfunction caused by immunosuppressive agents was common, and two patients required late renal transplantation. Lymphoproliferative disease or other neoplasm occurred in 12 patients, but none resulted in death. Coronary artery disease was diagnosed in 13 patients (19%), leading to retransplantation in eight. Death after 5 years was related to acute or chronic rejection in 5 of 8 cases. Two of the deaths were directly related to noncompliance with immunosuppressive medication. All survivors are in New York Heart Association class 1.Long-term survival with good quality of life can be achieved after heart transplantation in childhood, though complications of immunosuppression remain common. Posttransplantation coronary artery disease is emerging as the main factor limiting long term graft and patient survival.

    View details for Web of Science ID A1997XE50200008

    View details for PubMedID 9202606

  • Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis XVI International Congress of the Transplantation-Society Reichenspurner, H., Gamberg, P., Nitschke, M., Valantine, H., Hunt, S., Oyer, P. E., Reitz, B. A. ELSEVIER SCIENCE INC. 1997: 627–28

    View details for Web of Science ID A1997WM12700260

    View details for PubMedID 9123449

  • A rodent model of in utero chimeric tolerance induction JOURNAL OF HEART AND LUNG TRANSPLANTATION Yuh, D. D., Gandy, K. L., Hoyt, G., Reitz, B. A., Robbins, R. C. 1997; 16 (2): 222-230

    Abstract

    In utero tolerance induction has potential application in pediatric heart transplantation. Immunotolerance appears to be more easily induced in the fetus before full immunocompetence is established; however, the mechanisms behind this phenomenon are still undefined.One hundred thirty Lewis (RT1l) rat fetuses from 10 litters were inoculated intraperitoneally at 18 days gestation with 1 x 10(7) ACI (RT1a) rat fetal liver cells. Fifty of the 100 viable neonates successfully brought to term were grafted with neonatal ACI skin within 24 hours of birth and heterotopic ACI hearts at 8 to 10 weeks of age (group 1A); the remaining 50 neonates only received heterotopic ACI heart grafts at 8 to 10 weeks (group 1B). Control groups consisted of 50 Lewis fetuses (five litters) inoculated in utero with phosphate-buffered saline solution (group 2) and 50 Lewis fetuses (five litters) that received no inoculum (group 3); all of these surviving progeny received both neonatal ACI skin and adult ACI cardiac allografts. Skin and cardiac grafts were monitored by daily visual inspection and palpation, respectively. Limiting dilution analysis was performed among all groups to assess precursor cytotoxic lymphocyte frequencies. Likewise, peripheral blood lymphocyte and splenocyte populations were analyzed with flow cytometry to detect allogeneic chimerism.Abortion rates among groups 1, 2, and 3 were 23% (30/130 abortions), 10% (5/50 abortions), and 6% (3/50 abortions), respectively. Tolerance to both ACI skin and cardiac allografts was induced in 14 of the 50 group 1A Lewis recipients (28%). Tolerance was not achieved in any of the recipients in groups 1B, 2, or 3. Limiting dilution analysis among all groups revealed a marked reduction of precursor cytotoxic T-lymphocytes in tolerant allograft recipients compared with recipients in the other groups. Flow cytometry detected significant splenocyte chimerism among tolerant rats; significant peripheral blood chimerism was not noted.We describe allogeneic tolerance induction in utero to both rat skin and heart tissue by use of donor-strain fetal liver cells. Compared with previous studies with adult splenocytes as the tolerogen, we achieved a higher frequency of tolerance with a markedly lower cell inoculum and lower abortion rate. Allogeneic chimerism was noted in the tolerant recipients, suggesting hematopoietic stem cell engraftment. Cytotoxic T-lymphocyte precursor frequencies were markedly depressed in tolerant animals. Interestingly, both donor-strain fetal liver cells and neonatal skin grafts were required to induce tolerance. These data suggest a period of hematopoietic "education" during and shortly after hematopoietic stem cell engraftment.

    View details for Web of Science ID A1997WL96500009

    View details for PubMedID 9059934

  • Port-access bilateral internal mammary artery grafting for left main coronary artery disease: Canine feasibility study 76th Annual Meeting of the American-Association-for-Thoracic-Surgery Peters, W. S., Burdon, T. A., Siegel, L. C., Pompili, M. F., Stevens, J. H., STGOAR, F. G., Reichenspurner, H., FRISCHMEYER, K., Cohen, R., Reitz, B. A. BLACKWELL PUBLISHING. 1997: 1–7

    Abstract

    To extend the applications of minimal access cardiac surgery, an endovascular cardiopulmonary bypass (CPB) system that allows cardioplegia delivery and cardiac venting was used to perform bilateral internal mammary artery (IMA) bypass grafting in six dogs.The left IMA (LIMA) was taken down thoracoscopically from three left lateral chest ports, followed by the right IMA (RIMA) from the right side. One left-sided port was extended medially 5 cm with or without rib resection, to expose the pericardium. Both IMAs were divided and exteriorized through the left anterior mediastinotomy. Flow and pedicle length were satisfactory in all cases. Femoral-femoral bypass was used and the heart arrested with antegrade delivery of cardioplegic solution via the central lumen of a balloon catheter inflated to occlude the ascending aorta. All anastomoses were made through the mediastinotomy under direct vision. In five studies the RIMA was attached to the left anterior descending artery (LAD) and the LIMA to the circumflex, and in one study the RIMA was tunneled through the transverse sinus to the circumflex and the LIMA was anastomosed to the LAD. All animals were weaned from CPB in sinus rhythm without inotropes. CPB duration was 108 +/- 27 minutes (mean +/- SD) and the clamp duration was 54 +/- 10 minutes.Preoperative and postoperative cardiac outputs were 2.9 +/- 0.71/min and 2.4 +/- 0.31/min, respectively (p = NS), and corresponding pulmonary artery occlusion pressures were 6 +/- 3 mmHg and 7 +/- 2 mmHg, respectively (p = NS). All 12 grafts were demonstrated to be fully patent. Postmortem examination revealed well aligned pedicles and correctly grafted target vessels.This canine model demonstrates the potential for a less invasive approach to the surgical management of left main coronary artery disease in humans.

    View details for Web of Science ID A1997XU60700002

    View details for PubMedID 9169362

  • A single center experience with heart retransplantation: the 29 year experience at a single institution 29th Conference on Transplantation and Clinical Immunology Hunt, S. A., Robbins, R. C., Stinson, E. B., Dyer, P. E., Shumway, N. E., Reitz, B. A. KLUWER ACADEMIC PUBL. 1997: 229–236
  • Risk factors for the development of obliterative bronchiolitis after lung transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Girgis, R. E., Tu, I. P., Berry, G. J., Reichenspurner, H., Valentine, V. G., Conte, J. V., Ting, A., Johnstone, I., Miller, J., Robbins, R. C., Reitz, B. A., Theodore, J. 1996; 15 (12): 1200-1208

    Abstract

    Acute rejection has emerged as an important risk factor for obliterative bronchiolitis after lung transplantation. We performed a multivariate analysis to assess the impact of additional variables.Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung recipients) who survived longer than 90 days and underwent transplantation more than 15 months before data analysis were included in this study. Several variables were entered into a Cox regression analysis to determine their association with the development of bronchiolitis obliterans syndrome.Bronchiolitis obliterans syndrome developed in 48 (65%) of 74 patients. Significant correlations were detected for acute rejection score, defined as the sum of pathologic grades of each separate acute rejection episode (p = 0.0004, likelihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03). In a bivariate model, episodes of organizing pneumonia and bacterial or fungal pneumonia significantly increased the likelihood ratio test value of the acute rejection score. The addition of the cytomegalovirus infection score, reflecting the frequency and severity of infection, to the combination of the acute rejection score and episodes of bacterial or fungal pneumonia resulted in a further significant increase in the likelihood ratio test value. Significant risk factors for moderate to severe stages of airflow limitation were at least one episode of acute rejection of grade > or = 2, younger recipient age, and any acute rejection episode 180 days or longer after transplantation.Increasing frequency and severity of acute rejection episodes are strongly associated with the development of bronchiolitis obliterans syndrome. Lymphocytic bronchiolitis appeared to be significant by univariate analysis, but in a two-risk factor model, it did not augment the influence of acute rejection. Organizing pneumonia, bacterial or fungal pneumonia, and increasing severity and frequency of cytomegalovirus infections potentiate the effect of acute rejection. Late episodes of acute rejection and younger recipient age increase the risk for development of advanced disease.

    View details for Web of Science ID A1996WA94600005

    View details for PubMedID 8981205

  • Port-access mitral valve replacement in dogs 76th Annual Meeting of the American-Association-for-Thoracic-Surgery Pompili, M. F., Stevens, J. H., Burdon, T. A., Siegel, L. C., Peters, W. S., Ribakove, G. H., Reitz, B. A. MOSBY-ELSEVIER. 1996: 1268–74

    Abstract

    The objective was to assess mitral valve replacement in a minimally invasive fashion by means of port-access technology.Fifteen dogs, 28 +/- 3 kg (mean +/- standard deviation), were studied with the port-access mitral valve replacement system (Heartport, Inc., Redwood City, Calif.). Eleven dogs underwent acute studies and were sacrificed immediately after the procedure. Four dogs were allowed to recover and then were sacrificed 4 weeks after operation. Cardiopulmonary bypass was conducted by femoral cannulation with an endovascular balloon catheter for aortic occlusion, root venting, and antegrade delivery of cardioplegic solution. Catheters were inserted in the jugular vein for pulmonary artery venting and retrograde delivery of cardioplegic solution. Through the oval port, a prosthesis (St. Jude Medical, Inc., St. Paul, Minn., or CarboMedics, Inc., Austin, Texas) was inserted through the left atrial appendage and secured to the anulus with sutures. Deairing was performed.Cardiopulmonary bypass duration was 114 +/- 24 minutes and aortic crossclamp time was 68 +/- 14 minutes. All animals were weaned from cardiopulmonary bypass in sinus rhythm. Cardiac output and pulmonary artery occlusion pressure were unchanged (2.8 +/- 0.7 L/min and 7 +/- 3 mm Hg before operation vs 2.6 +/- 0.6 L/min and 9 +/- 4 mm Hg after operation). There was no mitral regurgitation according to left ventriculography in 13 of 15 dogs. In two dogs there was interference with prosthetic valve closure by residual native anterior leaflet tissue. Pathologic examination otherwise showed normal healing without perivalvular discontinuity. Microscopic studies showed no damage to the valve surfaces. Transthoracic echocardiography of the four dogs in the long-term study showed normal ventricular and prosthetic valve function 4 weeks after the operation.Mitral valve replacement with a minimally invasive method has been demonstrated in dogs. A clinical trial is in progress.

    View details for Web of Science ID A1996VV63200028

    View details for PubMedID 8911323

  • Tolerance to cardiac allografts induced in utero with fetal liver cells CIRCULATION Yuh, D. D., Gandy, K. L., Hoyt, G., Reitz, B. A., Robbins, R. C. 1996; 94 (9): 304-307
  • Stanford experience with obliterative bronchiolitis after lung and heart lung transplantation 32nd Annual Meeting of the Society-of-Thoracic-Surgeons Reichenspurner, H., Girgis, R. E., Robbins, R. C., Yun, K. L., Nitschke, M., Berry, G. J., Morris, R. E., Theodore, J., Reitz, B. A. ELSEVIER SCIENCE INC. 1996: 1467–72

    Abstract

    Obliterative bronchiolitis (OB) is the main chronic complication after heart-lung (HLTx) and lung transplantation (LTx), limiting the long-term success of both transplant procedures.Since 1981, 135 HLTxs and 61 isolated LTxs were performed in 184 patients at Stanford University.The overall prevalence of OB in patients surviving longer than 3 months postoperatively was 64% after HLTx and 68% after LTx. The actuarial freedom from OB was 72%, 51%, 44%, and 29% at 1, 2, 3, and 5 years, respectively, after HLTx and LTx. An analysis of potential risk factors revealed that the frequency and severity of acute rejection episodes (p < 0.001) and the appearance of lymphocytic bronchiolitis on biopsy (p < 0.05) were significantly associated with the development of OB. With regard to diagnosis of OB, pulmonary function tests show early reductions of the forced expiratory flow between 25% and 75% of the forced vital capacity with subsequent decreases in the forced expiratory volume in 1 second. The sensitivity of transbronchial biopsies has increased to 71% since 1993. Current treatment consists of augmented immunosuppression. Concurrent acute rejection episodes or active OB on biopsy have been treated aggressively with high-dose steroid pulses. Analysis of data from 73 patients with OB after HLTx and LTx revealed actuarial 1-, 3-, 5-, and 10-year survival of 89%, 71%, 44%, and 17% versus 86%, 77%, 63% and 56% in patients without OB (p < 0.05 by log-rank analysis). The main complication and cause of death in patients with OB was superimposed respiratory tract infection, which was treated aggressively.Early diagnosis of OB using pulmonary function tests or transbronchial biopsy is possible and important, because immediate treatment initiation has led to acceptable survival rates, with nearly 50% of affected patients still alive 5 years after transplantation. Current experimental research on OB suggests that immune injury is the main pathogenetic event of airway obliteration in animal models; rapamycin and leflunomide are new immunosuppressive agents that may have the potential to prevent and treat airway obliteration.

    View details for Web of Science ID A1996VQ16700050

    View details for PubMedID 8893585

  • Tolerance to cardiac allografts induced in utero with fetal liver cells. Circulation Yuh, D. D., Gandy, K. L., Hoyt, G., Reitz, B. A., Robbins, R. C. 1996; 94 (9): II304-7

    Abstract

    Induction of immunological tolerance in utero has potential application in pediatric cardiac transplantation. We describe an inexpensive, reproducible, and well-characterized model of allogeneic tolerance induction in utero using donorstrain fetal liver cells.Each of 9 Lewis (LEW, RTl1) rat fetuses in one litter (group 1) and 10 LEW fetuses in another litter (group 2) were inoculated intraperitoneally at 17 to 18 days of gestation with 1 x 10(6) ACI (RTla) rat fetal liver cells. Ten LEW fetuses in a third litter inoculated with PBS (group 3) and 10 LEW noninoculated fetuses in a fourth litter (group 4) served as controls. The LEW rats were brought to term, and groups 1, 3, and 4 were grafted with neonatal ACI skin within 24 hours of birth and with heterotopic ACI hearts at 8 to 10 weeks of age; group 2 rats received only an ACI heart graft at 8 to 10 weeks. Skin and cardiac grafts were monitored by daily visual inspection and palpation, respectively. Peripheral blood lymphocyte (PBL) populations in all LEW recipients were analyzed with flow cytometry. All LEW fetuses survived to term and developed normally. The ACI skin and cardiac allografts on 3 of the 9 LEW rats in group 1 are viable to date (skin, > 170 days; cardiac, > 100 days). The remaining 6 recipients of this group and all animals in groups 2, 3, and 4 rejected their skin and cardiac grafts by postgrafting day 7. Significant PBL chimerism (1.57%) was observed in only 1 tolerant rat.We describe allogeneic tolerance induction in utero to both rat skin and cardiac tissue with donor-strain fetal liver cells. Compared with previous studies using adult splenocytes as the tolerogen, we achieved a higher frequency of tolerance with a markedly lower cell inoculum and no abortions. Interestingly, both donor-strain fetal liver cells and neonatal skin grafts were required to maintain tolerance into adulthood. Immunocompetence sufficient to reject allografts was noted in neonates, and PBL chimerism was not prominent in tolerant recipients.

    View details for PubMedID 8901765

  • Twenty-year clinical experience with porcine bioprostheses 32nd Annual Meeting of the Society-of-Thoracic-Surgeons Fann, J. I., Miller, D. C., Moore, K. A., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Robbins, R. C., Reitz, B. A., Shumway, N. E. ELSEVIER SCIENCE INC. 1996: 1301–11

    Abstract

    For the past 25 years, porcine valves have been the most widely implanted bioprosthesis, thereby becoming the standard for comparison with newer bioprosthetic valves.We retrospectively analyzed 2,879 patients who underwent aortic (AVR; n = 1,594) or mitral (MVR; n = 1,285) valve replacement between 1971 and 1990. Follow-up was 97% complete and extended to 20 years (total, 17,976 patient-years). Patient age ranged from 16 to 94 years; mean age in patients who underwent AVR was 60 +/- 15 (+/- standard deviation) years; that for patients who underwent MVR was 58 +/- 13 years.The operative mortality rates were 7% +/- 1% (70% confidence limits) for AVR and 10% +/- 1% for MVR. Actuarial estimates of freedom from structural valve deterioration at 10 and 15 years were 78% +/- 2% (SE) and 49% +/- 4%, respectively, for the AVR subgroup; and 69% +/- 2% and 32% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from reoperation at 10 and 15 years were 76% +/- 2% and 53% +/- 4%, respectively, for the AVR subgroup and 70% +/- 2% and 33% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from thromboembolism at 10 and 15 years were 92% +/- 1% and 87% +/- 2%, respectively, for the AVR subgroup and 86% +/- 1% and 77% +/- 3%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from anticoagulant-related hemorrhage at 10 and 15 years were both 96% +/- 1% for the AVR subgroup and 93% +/- 1% and 90% +/- 2%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from valve-related mortality at 10 and 15 years were 86% +/- 1% and 78% +/- 3%, respectively, for the AVR subgroup and 84% +/- 2% and 70% +/- 4%, respectively, for the MVR subgroup (p = not significant). Multivariate analysis (Cox model) showed younger age, later year of operation, and valve site (MVR > AVR) to be significant risk factors for structural valve deterioration. Younger age, later year of operation, valve site (MVR > AVR), and renal insufficiency were the significant, independent risk factors for reoperation. Multivariate analysis revealed that higher New York Heart Association functional class, longer cardiopulmonary bypass time, congestive heart failure, renal insufficiency, and longer cross-clamp time were significant risk factors for valve-related mortality. Valve manufacturer did not emerge as a factor in any analysis.These long-term results with porcine bioprostheses were satisfactory, particularly in older patients and those undergoing AVR. As expected, younger age was a significant risk factor for structural valve deterioration and reoperation in both groups. Surprisingly, the durability of porcine bioprosthetic valves has not improved over time, which possibly can be attributed to more enhanced postoperative surveillance and earlier reintervention. These first-generation Hancock and Carpentier-Edwards porcine bioprostheses achieved similar long-term performance.

    View details for Web of Science ID A1996VQ16700014

    View details for PubMedID 8893561

  • Composite versus separate aortic valve and ascending aortic replacement - 30 year experience Yun, K. L., Fann, J. I., Miller, D. C., Mitchell, R. S., Robbins, R. C., Oyer, P. E., Stinson, E. B., Reitz, B. A., Shumway, N. E. LIPPINCOTT WILLIAMS & WILKINS. 1996: 1017–17
  • Port-access coronary artery bypass with cardioplegic arrest: Acute and chronic canine studies 32nd Annual Meeting of the Society-of-Thoracic-Surgeons Stevens, J. H., Burdon, T. A., Siegel, L. C., Peters, W. S., Pompili, M. F., STGOAR, F. G., Berry, G. J., Ribakove, G. H., Vierra, M. A., Mitchell, R. S., Toomasian, J. M., Reitz, B. A. ELSEVIER SCIENCE INC. 1996: 435–40

    Abstract

    Our goal is to perform minimally invasive coronary artery bypass grafting without sacrificing the benefits of myocardial protection with cardioplegia.Twenty-three dogs underwent acute studies and 4 dogs underwent survival studies. The left internal mammary artery was taken down using a thoracoscope. Cardiopulmonary bypass was conducted via femoral cannulas and using an endovascular balloon catheter for ascending aortic occlusion, root venting, and delivery of antegrade blood cardioplegia. Pulmonary artery venting was achieved with a jugular vein catheter. An internal mammary artery-to-coronary artery anastomosis was performed using a microscope through a 10 mm port.All animals were weaned from cardiopulmonary bypass in sinus rhythm without inotropes. Cardiopulmonary bypass duration was 104 +/- 28 minutes and aortic clamp duration was 61 +/- 22 minutes. Cardiac output and pulmonary artery occlusion pressure were unchanged. The internal mammary artery was anastomosed to the left anterior descending artery (25) or the first diagonal (2) with patency shown in 25 of 27. One dog in the survival study had a very short internal mammary artery pedicle under tension and was euthanized for excessive postoperative hemorrhage. Three weeks postoperatively the remaining dogs had angiographically patent anastomoses, normal transthoracic echocardiograms, and histologically normal healing and patent grafts.Endovascular cardiopulmonary bypass using a balloon catheter is effective in arresting and protecting the heart to allow thoracoscopic internal mammary artery-to-coronary artery anastomosis.

    View details for Web of Science ID A1996VA28700026

    View details for PubMedID 8694602

  • Pediatric heart-lung transplantation: Intermediate-term results JOURNAL OF HEART AND LUNG TRANSPLANTATION Conte, J. V., Robbins, R. C., Reichenspurner, H., Valentine, V. G., Theodore, J., Reitz, B. A. 1996; 15 (7): 692-699

    Abstract

    Adult heart-lung transplantation was initiated at Stanford in 1981 and the first pediatric heart-lung transplantation was done in 1986. Intermediate-term results of pediatric heart-lung transplantation at Stanford University are presented.A retrospective review of the records of all pediatric heart-lung transplantations done since 1986 was conducted.Nineteen heart-lung transplantations were done in 17 patients. Ages ranged from 2 months to 18 years with a median age of 10 years. At the time of transplantation 5 patients were infants, 7 children, and 7 adolescents. The mean follow-up was 29 +/- 6.2 months (range 1 to 77, median 16) and follow-up was 100% complete. Diagnoses were congenital heart disease in 13, primary pulmonary hypertension in 2, and cystic fibrosis, cystic lymphangiectasia, viral pneumonia, and obliterative bronchiolitis in 1 each. Median wait on the heart-lung transplantation list was 91 days (range 2 to 707). All patients had New York Heart Association class III to IV symptoms, two were receiving ventilator support, and six were receiving oxygen. Fifteen of 19 transplant recipients were discharged from the hospital. The 30-day operative mortality rate was 5.2% (1 of 19). The actuarial survival at 1, 3, and 5 years for all patients was 67%, 51%, and 41%, respectively, and for hospital survivors was 82%, 62%, and 51%. The cause of death was obliterative bronchiolitis in 4, multisystem organ failure in 3, and graft coronary artery disease and chronic airway disease in 1 each. Three patients required retransplantation, 2 because of obliterative bronchiolitis and 1 because of viral pneumonia. Two patients underwent repeat heart-lung transplantation and 1 patient underwent single lung transplantation. Rejection was diagnosed in 73% of recipients, and obliterative bronchiolitis has developed in 32% of recipients.Survival in pediatric heart-lung transplantation approximates that in the adult procedure at 1, 3, and 5 years. Long-term survival has been achieved but the primary factors limiting further improved survival remain infection and obliterative bronchiolitis.

    View details for Web of Science ID A1996VA15400004

    View details for PubMedID 8820785

  • Obliterative airway disease after heterotopic tracheal xenotransplantation in a concordant rodent model: Pathogenesis and treatment 3rd International Congress for Xenotransplantation Reichenspurner, H., Adams, B., Soni, V., Brazelton, T., Shorthouse, R., Reitz, B. A., Berry, G. J., Morris, R. E. ELSEVIER SCIENCE INC. 1996: 729–30

    View details for Web of Science ID A1996UG38300121

    View details for PubMedID 8623368

  • Actuarial survival of heart-lung and bilateral sequential lung transplant recipients with obliterative bronchiolitis JOURNAL OF HEART AND LUNG TRANSPLANTATION Valentine, V. G., Robbins, R. C., Berry, G. J., Patel, H. R., Reichenspurner, H., Reitz, B. A., Theodore, J. 1996; 15 (4): 371-383

    Abstract

    Obliterative bronchiolitis is a progressive form of obstructive airway disease that threatens long-term survival in lung transplant recipients. Its incidence and the long-term survival of lung transplant recipients with obliterative bronchiolitis are unknown.The results of 89 heart-lung and 13 bilateral sequential lung transplant survivors beyond 90 days of their operation were analyzed. The date of diagnosis for obliterative bronchiolitis was established histologically (presence of submucosal fibrosis) or physiologically by a persistent reduction in the forced vital capacity to less than 0.7 for greater than 6 weeks. There were 43 patients without obliterative bronchiolitis and 59 patients with obliterative bronchiolitis.No differences were found in the mean age and gender ratios between the two groups. The actuarial 1-, 5-, and 10-year percentage freedom from obliterative bronchiolitis was 72 +/- 4.6, 30 +/- 5.6, and 15 +/- 7.4, respectively, with a median onset of 689 days (range 55 to 3404 days). About half the patients with biopsy-proven obliterative bronchiolitis had a fall in their forced expiratory flow at 50% of forced vital capacity/forced vital capacity nearly 4 months before fulfilling the forced expiratory volume in 1 second criteria established by the Working Group on chronic lung dysfunction. The actuarial 1-, 5-, and 10-year percentage survival of obliterative bronchiolitis negative patients was 90 +/- 4.5, 74 +/- 8.4, and 66 +/- 10.6, respectively, versus 90 +/- 3.9, 49 +/- 6.9, and 27 +/- 10.0, respectively, for obliterative bronchiolitis positive patients (p = 0.38). The actuarial 1-, 3-, 5-, 8-, and 10-year percentage survival of lung transplant recipients after the diagnosis of obliterative bronchiolitis was 74 +/- 5.8, 50 +/- 7.5, 43 +/- 7.8, 23 +/- 8.7, and 11 +/- 9.1, respectively, with a median survival of 1084 days (range 0 to 3442 days).The forced expiratory flow at 50% of forced vital capacity/forced vital capacity is a more sensitive indicator for the early detection of obliterative bronchiolitis than the forced expiratory volume in 1 second after heart-lung or bilateral sequential lung transplantation. The obliterative bronchiolitis negative group survival tends to be better than the obliterative bronchiolitis positive group. The obliterative bronchiolitis positive lung transplant recipients have reasonable outcomes with a median survival time of nearly 3 years after the diagnosis of obliterative bronchiolitis. Earlier detection of obliterative bronchiolitis and refinements in management may further improve these results.

    View details for Web of Science ID A1996UJ09600006

    View details for PubMedID 8732596

  • Port-access coronary artery bypass grafting: A proposed surgical method JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Stevens, J. H., Burdon, T. A., Peters, W. S., Siegel, L. C., Pompili, M. F., Vierra, M. A., STGOAR, F. G., Ribakove, G. H., Mitchell, R. S., Reitz, B. A. 1996; 111 (3): 567-573

    Abstract

    Minimally invasive surgical methods have been developed to provide patients the benefits of open operations with decreased pain and suffering. We have developed a system that allows the performance of cardiopulmonary bypass and myocardial protection with cardioplegic arrest without sternotomy or thoracotomy. In a canine model, we successfully used this system to anastomose the internal thoracic artery to the left anterior descending coronary artery in nine of 10 animals. The left internal thoracic artery was dissected from the chest wall, and the pericardium was opened with the use of thoracoscopic techniques and single lung ventilation. The heart was arrested with a cold blood cardioplegic solution delivered through the central lumen of a balloon occlusion catheter (Endoaortic Clamp; Heartport, Inc., Redwood City, Calif.) in the ascending aorta, and cardiopulmonary bypass was maintained with femorofemoral bypass. An operating microscope modified to allow introduction of the 3.5x magnification objective into the chest was positioned through a 10 mm port over the site of the anastomosis. The anastomosis was performed with modified surgical instruments introduced through additional 5 mm ports. In the cadaver model (n = 7) the internal thoracic artery was harvested and the pericardium opened by means of similar techniques. A precise arteriotomy was made with microvascular thoracoscopic instruments under the modified microscope on four cadavers. In three other cadavers we assessed the exposure provided by a small anterior incision (4 to 6 cm) over the fourth intercostal space. This anterior port can assist in dissection of the distal internal thoracic artery and provides direct access to the left anterior descending, circumflex, and posterior descending arteries. We have demonstrated the potential feasibility of grafting the internal thoracic artery to coronary arteries with the heart arrested and protected, without a major thoracotomy or sternotomy.

    View details for Web of Science ID A1996UB98000013

    View details for PubMedID 8601971

  • The utility of annual surveillance bronchoscopy in heart-lung transplant recipients 14th Annual Meeting of the American-Society-of-Transplant-Physicians Girgis, R. E., Reichenspurner, H., Robbins, R. C., Reitz, B. A., Theodore, J. WILLIAMS & WILKINS. 1995: 1458–61

    Abstract

    Bronchoscopy with transbronchial biopsy (TBBx) and bronchoalveolar lavage (BAL) has an appreciable yield in detecting asymptomatic abnormalities in heart-lung transplant recipients (HLTR) during the early postoperative period. The utility of annual surveillance procedures has not been critically evaluated. We reviewed all annual bronchoscopies performed on 29 HLTR to determine the frequency of asymptomatic abnormalities. Surveillance bronchoscopies (SB) were performed on asymptomatic subjects with unchanged lung function compared with baseline. Surveillance/clinical bronchoscopies (SCB) were those performed in patients with stable decrements in lung function. Nineteen patients underwent 48 SB and 8 had 18 SCB. Five of 15 (33%) SB performed at one year yielded an abnormal TBBx (1 grade 2 acute rejection [AR], 1 grade 1 AR, 1 grade 1 AR with obliterative bronchiolitis [OB] and 2 Pneumocystis carinii pneumonia). At 2 or more years, TBBx was abnormal in 2 of 33 (6%, p = 0.024 compared with first year TBBx) (1 grade 1 AR, 1 lymphocytic bronchiolitis). Pathogens were identified in BAL in 19 (40%) SB. Fourteen (78%) SCB were abnormal. Nine (50%) revealed an abnormal TBBx (all OB), but only 2 (11%) of these altered patient management. Seven (39%) demonstrated pathogens in BAL. We conclude that in HLTR (1) surveillance TBBx rarely yields positive findings 2 or more years posttransplant, (2) surveillance TBBx seldom alters management in patients with stable decrements in lung function, and (3) BAL is useful to screen for potential pathogens.

    View details for Web of Science ID A1995TN23000015

    View details for PubMedID 8545874

  • Obliterative bronchiolitis after lung and heart-lung transplantation ANNALS OF THORACIC SURGERY Reichenspurner, H., Girgis, R. E., Robbins, R. C., Conte, J. V., Nair, R. V., Valentine, V., Berry, G. J., Morris, R. E., Theodore, J., Reitz, B. A. 1995; 60 (6): 1845-1853

    Abstract

    Obliterative bronchiolitis (OB) has emerged as the main cause of morbidity and mortality in the long-term follow-up after lung and heart-lung transplantation. The pathogenesis of OB is multifactorial, with acute rejection and cytomegalovirus infection being the main risk factors for the development of OB. The final common pathway of all inciting events seems to be an alloimmune injury, with subsequent release of immunologic mediators and production of growth factors leading to luminal obliteration and fibrous scarring of the small airways. Analyzing the 14 years of experience in 163 patients at Stanford University, we found a current incidence of bronchiolitis obliterans syndrome or histologically proven OB within the first 3 years after lung and heart-lung transplantation of 36.3%, with an overall prevalence of 58.1% after heart-lung and 51.4% after lung transplantation. Both pulmonary function indices (forced expiratory flow between 25% and 75% of forced vital capacity and forced expiratory volume in 1 second) and transbronchial biopsies have proven helpful in diagnosing bronchiolitis obliterans syndrome or OB at an early stage. Early diagnosis of OB and improved management have achieved survival rates in patients with OB after 1, 3, 5, and 10 years of 83%, 66%, 46%, and 22%, compared with 86%, 83%, 67%, and 67% in patients without OB. Recently, different experimental models have been developed to investigate the cellular and molecular events leading to OB and to evaluate new treatment strategies for this complication, which currently limits the long-term success of heart-lung and lung transplantation.

    View details for Web of Science ID A1995TV39200074

    View details for PubMedID 8787504

  • The use of neonatal blood to reconstitute lethally irradiated animals across major histocompatibility barriers and to facilitate subsequent solid organ alloengraftment in the rodent. Gandy, K. L., Morrison, S. J., Reitz, B. A., Weissman, I. L., CLAYBERGER, C. AMER SOC HEMATOLOGY. 1995: 2274–74
  • Leflunomide prolongs pulmonary allograft and xenograft survival JOURNAL OF HEART AND LUNG TRANSPLANTATION Yuh, D. D., Gandy, K. L., Morris, R. E., Hoyt, G., Gutierrez, J., Reitz, B. A., Robbins, R. C. 1995; 14 (6): 1136-1144

    Abstract

    Leflunomide, an isoxazole derivative, has been shown to effectively prolong rodent allograft and cardiac xenograft survival. In vitro studies suggest that leflunomide inhibits the production of donor-specific antibodies and is capable of blocking both T- and B-cell proliferation. In light of the significant role that humoral immunity is believed to play in chronic pulmonary allograft rejection as well as hyperacute and accelerated acute xenograft rejection, we examined the efficacy of leflunomide in prolonging pulmonary allografts and xenografts and its effect on donor-specific antibody production.Lungs from Brown Norway rats or Golden Syrian hamsters were orthotopically transplanted into Lewis rat recipients. Allograft recipients were treated daily for 14 days with vehicle, leflunomide (15 mg/kg/day orally), or cyclosporine (7.5 mg/kg/day orally) starting on the day of grafting (day 0). In xenograft recipients, leflunomide (20 mg/kg/day orally) or cyclosporine (7.5 mg/kg/day orally) treatment initiated on day 0 was continued until complete graft rejection; the leflunomide dosage was reduced to 10 mg/kg/day after day 14 because of weight loss and leukopenia. Graft viability was assessed with chest radiography in conjunction with open lung biopsies. Toxicity was monitored with body weight measurements, complete blood counts, and serum chemistries. Flow cytometric analysis of serum samples taken from graft recipients on day 7 was used to measure donor-specific immunoglobulin M and immunoglobulin G antibody titers.Allograft and xenograft control animals receiving vehicle yielded graft survival times of 6.0 +/- 0.0 and 5.4 +/- 0.6 days, respectively. Although xenograft recipients treated with cyclosporine (7.5 mg/kg/day orally) showed no significant graft prolongation, pulmonary allograft survival in recipients receiving cyclosporine alone was significantly prolonged to 28.2 +/- 0.7 days. Leflunomide-treated allograft (15 mg/kg/day orally) and xenograft (20 mg/kg/day orally) recipients displayed significant graft prolongation to 28.2 +/- 0.7 days and 15.8 +/- 3.3 days, respectively. Cyclosporine (7.5 mg/kg/day orally) enhanced the effect of leflunomide (20 mg/kg/day orally) in xenograft recipients with a mean graft survival time of 36.0 +/- 3.0 days achieved when both drugs were administered concomitantly. Cyclosporine significantly suppressed donor-specific immunoglobulin G antibody titers in both pulmonary allograft and xenograft recipients while not affecting immunoglobulin M levels. Leflunomide markedly suppressed both immunoglobulin G and immunoglobulin M donor-specific antibody titers in allograft and xenograft recipients. Except for mild leukopenia and anemia, both cyclosporine- and leflunomide-treated allograft recipients showed no evidence of toxic side effects after 14 days of therapy. However, leflunomide-treated xenograft recipients displayed significant weight loss, anemia, and leukopenia after 14 days of treatment with one death in each treatment group.

    View details for Web of Science ID A1995TM55700018

    View details for PubMedID 8719461

  • SURGICAL-MANAGEMENT OF AORTIC DISSECTION DURING A 30-YEAR PERIOD CIRCULATION Fann, J. I., Smith, J. A., Miller, D. C., Mitchell, R. S., Moore, K. A., Grunkemeier, G., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1995; 92 (9): 113-121
  • Surgical management of aortic dissection during a 30-year period. Circulation Fann, J. I., Smith, J. A., Miller, D. C., Mitchell, R. S., Moore, K. A., Grunkemeier, G., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1995; 92 (9): II113-21

    Abstract

    Certain recent studies have demonstrated improved surgical outcome in patients with aortic dissection. We analyzed the surgical survival rates of patients with acute aortic dissections and the late prognosis of those with aortic dissection during a 30-year period.Between 1963 and 1992, 360 patients (256 men and 104 women; mean +/- 1 SD age, 57 +/- 14 years) underwent surgery for aortic dissection: 174 patients had an acute type A (AcA), 46 an acute type B (AcB), 106 a chronic type A (ChA), and 34 a chronic type B (ChB) aortic dissection. The overall operative mortality rate was 24 +/- 8% (26 +/- 3% for AcA, 39 +/- 8% for AcB, 17 +/- 4% for ChA, and 15 +/- 6% for ChB, [+/- 70% confidence limit]). The operative mortality rates for patients with acute aortic dissection (AcA or AcB) were assessed for five time "windows": 1963 to 1972 (42 +/- 8%), 1973 to 1977 (37 +/- 8%), 1978 to 1982 (15 +/- 6%), 1983 to 1987 (27 +/- 6%), and 1988 to 1992 (26 +/- 6%). Logistic regression analysis suggested that the low operative mortality rate during the 1978-to-1982 interval occurred by chance. Multivariate analysis showed earlier operative year, hypertension, cardiac tamponade, renal dysfunction, and older age were independent determinants of operative death. Actuarial survival rates (including early deaths) after 5, 10, and 15 years for AcA patients were 55%, 37%, and 24%; for AcB, 48%, 29%, and 11%; for ChA, 65%, 45%, and 27%; and for ChB, 59%, 45%, and 27%. Multivariate analysis revealed that older age and previous operation were significant predictors for late death. Freedom from reoperation for all patients was 84%, 67%, and 57% at 5, 10, and 15 years, respectively.Although the operative mortality rate decreased over time for patients with aortic dissection, the risk for those with acute aortic dissection during the last 10 years (1983 to 1992) is probably more realistic than that observed in the preceding 5-year interval (1978 to 1982). The operative mortality rates for patients with chronic aortic dissection have remained relatively static. Earlier diagnosis of acute aortic dissection before development of cardiac tamponade and renal impairment is critical to improve the operative salvage rate. Long-term outcome still is not optimal, which emphasizes the need for better serial postoperative aortic imaging surveillance and medical follow-up and blood pressure control.

    View details for PubMedID 7586393

  • HEART RETRANSPLANTATION - THE 25-YEAR EXPERIENCE AT A SINGLE INSTITUTION JOURNAL OF HEART AND LUNG TRANSPLANTATION Smith, J. A., Ribakove, G. H., Hunt, S. A., Miller, J., Stinson, E. B., Oyer, P. E., Robbins, R. C., Shumway, N. E., Reitz, B. A. 1995; 14 (5): 832-839

    Abstract

    The current critical shortage of cardiac allograft donors means that the decision to offer a patient repeat heart transplantation must be carefully considered. Since 1968, a total of 66 heart retransplantation procedures (63 first-time and three second-time) have been performed in 63 patients at Stanford.There were 52 male and 11 female patients, ranging in age from 3 to 62 years with a mean age of 41 years. Indications for retransplantation were primary allograft failure in nine patients, acute rejection in 17, graft atherosclerosis in 37, and constrictive disease in three. Six of the seventeen patients (35%) who underwent retransplantation before 1981 died in the hospital, and none are currently alive. Of the 46 patients who underwent retransplantation since 1981 treated with cyclosporine-based immunosuppression, 11 (24%) died in the hospital. Actuarial survival estimates for the whole retransplantation group at 1, 5, and 10 years were 55% +/- 8%, 33% +/- 8%, and 22% +/- 7%, respectively.This survival was significantly worse (p < 0.05) than that in patients undergoing primary heart transplantation (81% +/- 2%, 62% +/- 2%, 44% +/- 13% at 1, 5, and 10 years). Those patients who underwent retransplantation for graft atherosclerosis since 1981 had a significantly better 1-year survival (p < 0.05) than those who underwent retransplantation for allograft rejection (69% +/- 10% versus 33% +/- 16%), but the 5-year survival was similar in both groups (34% +/- 11% versus 33% +/- 16%). Since 1981, actuarial freedoms from infection and rejection were 22% +/- 8% and 41% +/- 9%, respectively, at 1 year, and 7% +/- 7% and 36% +/- 9% at 5 years. Patients with cyclosporine-induced renal dysfunction (serum creatinine level of greater than 2.0 mg/dl) had a high probability of requiring postoperative dialysis and also of death after retransplantation. Three patients with significant cyclosporine-induced renal dysfunction underwent simultaneous kidney transplantation and heart retransplantation, and all were alive and well at the time this article was written. Sixteen patients were also currently alive at a mean follow-up of 44 months, and 15 were in New York Heart Association functional class I.We continue to list carefully selected candidates with good rehabilitation potential for heart retransplantation.

    View details for Web of Science ID A1995RY62700004

    View details for PubMedID 8800717

  • DURABILITY OF THE HANCOCK-MO BIOPROSTHESIS COMPARED WITH STANDARD AORTIC-VALVE BIOPROSTHESES VI International Symposium for Cardiac Bioprostheses Yun, K. L., Miller, D. C., Moore, K. A., Mitchell, R. S., Oyer, P. E., Stinson, E. B., Robbins, R. C., Reitz, B. A., Shumway, N. E. ELSEVIER SCIENCE INC. 1995: S221–S228

    Abstract

    To compare the durability of the Hancock modified orifice (Hancock MO, model 250 [H-MO]) valve with two other commonly used standard aortic valve bioprostheses, a cohort of 1,602 patients undergoing aortic valve replacement using porcine valves between 1971 and 1990 (excluding simultaneous mitral valve replacement) was analyzed retrospectively using Cox model multivariate techniques. Five hundred sixty-one patients received a composite H-MO valve, 652 received a standard Hancock model 242 (H) valve, and 389 received a Carpentier-Edwards model 2625 (C-E) valve. Mean age was 60 +/- 15 years (+/- 1 standard deviation) (71% male). Follow-up (10,247 patient-years) extended to 15 years and was 97% complete. The main focus of this study was bioprosthetic durability, using The American Association for Thoracic Surgery/The Society of Thoracic Surgeons guidelines to define structural valve deterioration (SVD). Multivariate analysis revealed that (younger) age (p < 10(-5), liver disease (p = 0.02), and 1981 to 1985 operative period (p = 0.012) were the only significant, independent predictors of SVD. In concordance with previous reports, the SVD freedom estimate was greater than 90% at 15 years for patients older than 70 years of age. Hepatic dysfunction had an adverse effect on SVD (estimated freedom from event at 10 years was 34 +/- 17% [standard error of mean] versus 78 +/- 2% for those without liver disease), but this affected only 3% of patients. Interestingly, one operative period (1981 to 1985) was associated with a slightly higher risk of SVD compared to the three other 5-year time windows. Valve type did not emerge as a significant risk factor for SVD.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1995RT15700035

    View details for PubMedID 7646163

  • ARTERIAL SWITCH AND RESECTION OF HEPATIC HEMANGIOENDOTHELIOMA ANNALS OF THORACIC SURGERY Robbins, R. C., Chin, C., Yun, K. L., Berry, G. J., Bernstein, D., Reitz, B. A. 1995; 59 (6): 1575-1577

    Abstract

    We report on the management of a neonate undergoing arterial switch for transposition of the great arteries and concomitant resection of a hepatic infantile hemangioendothelioma. A preoperative aortogram demonstrated the arterial supply of the hepatic hemangioendothelioma. Pulmonary artery hypertension and myocardial ischemia were noted after separation from cardiopulmonary bypass. Resection of the hepatic malformation produced an immediate reduction in pulmonary hypertension and resolution of the myocardial ischemia. The patient had an uneventful postoperative recovery.

    View details for Web of Science ID A1995RB62100052

    View details for PubMedID 7771849

  • IN-VIVO STUDIES OF THE MAINTENANCE OF PERIPHERAL TRANSPLANT TOLERANCE AFTER CYCLOSPORINE - RADIOSENSITIVE ANTIGEN-SPECIFIC SUPPRESSOR CELLS MEDIATE LASTING GRAFT PROTECTION AGAINST PRIMED EFFECTOR-CELLS TRANSPLANTATION Nisco, S. J., Hissink, R. J., Vriens, P. W., Hoyt, E. G., Reitz, B. A., CLAYBERGER, C. 1995; 59 (10): 1444-1452

    Abstract

    Cellular mechanisms responsible for maintenance of peripheral transplant tolerance in a rodent model were evaluated. Donor-specific tolerance was established in ACI rats given a vascularized heterotopic cardiac allograft followed by a 10-day course of cyclosporine. Tolerance was associated with a reduction in donor-specific cytotoxic T lymphocyte precursors and the presence within the spleen of cells capable of transferring suppression in adoptive transfer assays. Experiments using thymectomized animals revealed that the establishment and maintenance of tolerance occurred peripherally, independently of the thymus. Adoptive transfer experiments demonstrated that ongoing graft tolerance was mediated by suppressor cells that were antigen-restricted, radiosensitive, and capable of preventing allograft rejection by naive as well as sensitized cells in vivo. Studies designed to disrupt tolerance demonstrated a remarkable durability of graft protection once established, and give insight into the identity and mechanism of action of suppressor cells generated in this model.

    View details for Web of Science ID A1995RB42900015

    View details for PubMedID 7539554

  • Diagnosis of acute pulmonary rejection episodes after lung- and heart-lung transplantation 4th International Symposium on Nursing, Coordinating, Bridging and Rehabilitation in Organ Transplantation/1st International Meeting of Organ Recipients Reichenspurner, H., Berry, G., Reichart, B., Reitz, B. A. ELSEVIER SCIENCE PUBL B V. 1995: 141–144
  • PEDIATRIC CARDIAC TRANSPLANTATION - THE STANFORD EXPERIENCE 66th Scientific Sessions of the American-Heart-Association:Cardiovascular Surgery 1993 Sarris, G. E., Smith, J. A., Bernstein, D., Griffin, M. L., Pitlick, P. T., Baum, D., Billingham, M. E., Oyer, P. E., Stinson, E. B., Starnes, V. A., Shumway, N. E., Reitz, B. A. AMER HEART ASSOC. 1994: 51–55
  • SURGICAL-MANAGEMENT OF AORTIC DISSECTION IN PATIENTS WITH THE MARFAN-SYNDROME 66th Scientific Sessions of the American-Heart-Association:Cardiovascular Surgery 1993 Smith, J. A., Fann, J. I., Miller, D. C., Moore, K. A., DeAnda, A., Mitchell, R. S., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. AMER HEART ASSOC. 1994: 235–42
  • CLOSED-CHEST CORONARY-ARTERY BYPASS WITH CARDIOPLEGIC ARREST IN THE DOG Stevens, J. H., Siegel, L. C., Mitchell, R. S., Burdon, T. A., Ribakove, G. H., Smith, J. A., STGOAR, F. G., Peters, W. S., Vierra, M. A., Pompili, M. F., Reitz, B. A. LIPPINCOTT WILLIAMS & WILKINS. 1994: 251–51
  • LONG-TERM SURVIVORS OF PEDIATRIC HEART-TRANSPLANTATION - A MULTICENTER REPORT OF 65 CHILDREN WHO HAVE SURVIVED GREATER-THAN 5 YEARS Sigfusson, G., Fricker, F. J., Lawrence, K., Miller, S. A., Armitage, J. M., Bernstein, D., Baum, D., Hunt, S. A., Miller, J., Reitz, B. A., Stinson, E. B., Hsu, D. T., Addonizio, L. J., Rose, E. A. LIPPINCOTT WILLIAMS & WILKINS. 1994: 97–97
  • SURGICAL-MANAGEMENT OF AORTIC DISSECTION OVER 30 YEARS Fann, J. I., Smith, J. A., Miller, D. C., Mitchell, R. S., Moore, K., Oyer, P. E., STINSOUN, E. B., Reitz, B. A., Shumway, N. E. LIPPINCOTT WILLIAMS & WILKINS. 1994: 96–96
  • CARDIAC TRANSPLANTATION - THE STANFORD EXPERIENCE IN THE CYCLOSPORINE ERA JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Sarris, G. E., Moore, K. A., Schroeder, J. S., Hunt, S. A., Fowler, M. B., VALANTINE, H. B., Vagelos, R. H., Billingham, M. E., Oyer, P. E., Stinson, E. B., Reitz, B. A., Shumway, N. E. 1994; 108 (2): 240-252

    Abstract

    We analyzed our experience with 496 patients who underwent primary cardiac transplantation since the introduction of cyclosporine immunosuppression (Dec. 16, 1980, to Jan. 7, 1993). There were 388 male and 108 female patients. Mean recipient age was 40 +/- 16 years (range 0.1 to 70 years, median 44 years). Recipient diagnoses included coronary disease in 188, idiopathic cardiomyopathy in 196, viral cardiomyopathy in 35, and congenital heart disease in 28 patients. Donor age was 25 +/- 10 years (range 1 to 53 years, median 24 years). Graft ischemic time was 148 +/- 57 minutes (range 38 to 495 minutes, median 149 minutes). Operative mortality (hospital death) rate was 7.9% +/- 1.3% (70% confidence intervals). Multivariate logistic regression analysis revealed that (higher) pulmonary vascular resistance and gender (female) were the only independent predictors of hospital death (p < 0.05). Actuarial survival estimates for all patients at 1, 5, and 10 years are 82% +/- 1.7% (83% +/- 1.8% adult, 77% +/- 5.2% pediatric), 61% +/- 2.5% (65% +/- 2.5% adult, 64% +/- 6.6% pediatric), and 41% +/- 3.7% (40% +/- 4% adult, 54% +/- 8.6% pediatric), respectively. For 232 patients treated with triple-drug immunosuppression and induction with OKT3 since 1987, survival estimates at 1 and 5 years are 82% +/- 2.6% and 67% +/- 3.7%, respectively. Causes of death for the entire group were rejection in 29 (14% of deaths), infection in 69 (34%), graft coronary disease in 36 (18%), nonspecific graft failure in 6 (3%), malignancy in 19 (10%), stroke in 6 (3%), pulmonary hypertension in 6 (3%), and other causes in 30 (15%) patients. Actuarial freedom from rejection at 3 months, 1 year, and 5 years was 21% +/- 1.9%, 14% +/- 1.7%, and 7.2% +/- 1.5%, respectively (+/- 1 standard error of the mean). Estimates of freedom from rejection-related death at 1, 5, and 10 years were 96% +/- 1%, 93% +/- 1.4%, and 93% +/- 1.4%, respectively. Actuarial freedom from any infection at 3 months and at 1 and 5 years was 40% +/- 2.3%, 27% +/- 2.1%, and 15% +/- 2.0% and from infection-related death, 95% +/- 1.0%, 93% +/- 1.2%, and 85% +/- 1.9%, respectively. Actuarial freedom from (angiographic or autopsy proved) graft coronary artery disease at 1, 5, and 10 years was 95% +/- 1.2%, 73% +/- 2.7%, and 65% +/- 3.6% and from coronary disease-related death or retransplantation 98% +/- 0.7%, 84% +/- 2.2%, and 66% +/- 4.3%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for Web of Science ID A1994PB11400006

    View details for PubMedID 8041172

  • SUCCESSFUL THROMBOLYSIS OF A THROMBOSED ST-JUDE MEDICAL MITRAL PROSTHESIS IN A 2-MONTH-OLD INFANT JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Smith, J. A., Desai, K., Bernstein, D., Reitz, B. A. 1994; 108 (1): 187-187

    View details for Web of Science ID A1994NW67700034

    View details for PubMedID 8028369

  • DEVELOPMENTS IN CARDIAC TRANSPLANTATION CURRENT OPINION IN CARDIOLOGY Nisco, S. J., Reitz, B. A. 1994; 9 (2): 237-246

    Abstract

    Cardiac transplantation has matured as a therapeutic intervention, allowing definitive treatment of critically ill children and adults with end-stage heart disease. The ongoing critical shortage of donor organs continues to deny hundreds of individuals access to this intervention. Accordingly, many of the most meaningful recent advances made in the field of cardiac transplantation involve means of expanding our donor pool. While current immunosuppressive regimens have been considerably successful in the management of acute cellular rejection, management of the problems of acute and chronic vascular rejection remains disappointing. Advances in this arena remain particularly urgent for physicians and surgeons involved in the care of heart transplant recipients.

    View details for Web of Science ID A1994NC26700014

    View details for PubMedID 8199391

  • Randomized, prospective assessment of bioprosthetic valve durability. Hancock versus Carpentier-Edwards valves. Circulation Sarris, G. E., Robbins, R. C., Miller, D. C., Mitchell, R. S., Moore, K. A., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1993; 88 (5): II55-64

    Abstract

    Although the major limitation of porcine valves is their finite durability, no controlled clinical data exist regarding the relative durability of the two porcine bioprostheses implanted most commonly today, the Carpentier-Edwards (C-E) and Medtronic Hancock I (H) valves.To assess this question, 174 patients undergoing aortic (AVR) or mitral (MVR) valve replacement with a bioprosthesis between March 1980 and March 1982 were randomized to receive either a C-E or a H valve. There were 102 AVRs (54 C-E and 48 H) and 74 MVRs (39 C-E and 35 H). For both the AVR and MVR cohorts, the average patient age was 58 +/- 14 years (+/- SD). The male/female ratio was 2.2:1 for AVR and 0.57:1 for MVR. Clinical follow-up was undertaken periodically; the most recent follow-up closing interval was July through October 1992, and current follow-up was 96% complete. Cumulative follow-up totaled 1369 patient-years (mean, 7.7 +/- 3.6 years; median, 9.1 years; maximum, 12.0 years). The main focus of this analysis was bioprosthetic durability, using the AATS/STS guidelines defining "Structural Valve Deterioration" (SVD). Multivariate analysis revealed that (younger) age was the only significant (P = .024) independent predictor of SVD. Valve manufacturer (C-E versus H) and valve site (aortic versus mitral) did not emerge as significant independent risk factors for SVD. Actuarial rates (Cutler-Ederer) expressed as percent free of SVD (+/- SEM) at 10 years (n = number of patients remaining at risk) were 71 +/- 7% and 59 +/- 9% for the C-E (n = 26) and H (n = 17) groups, respectively, for the AVR cohort; for the MVR cohort, these estimates were 60 +/- 10% (n = 12) and 72 +/- 10% (n = 11), respectively, but these differences were not statistically significant (P = NS, Lee-Desu).After 10 years, there was no statistically significant difference in durability or other valve-related complications between the H and C-E aortic or mitral valves. Based on current information, the choice of a porcine bioprosthesis should be based on factors other than durability, including ease of implantation, hemodynamic performance, and cost.

    View details for PubMedID 8222197

  • RANDOMIZED, PROSPECTIVE ASSESSMENT OF BIOPROSTHETIC VALVE DURABILITY - HANCOCK VERSUS CARPENTIER-EDWARDS VALVES CIRCULATION Sarris, G. E., Robbins, R. C., Miller, D. C., Mitchell, R. S., Moore, K. A., Stinson, E. B., Oyer, P. E., Reitz, B. A., Shumway, N. E. 1993; 88 (5): 55-64
  • PEDIATRIC HEART-LUNG AND LUNG TRANSPLANTATION PROGRESS IN PEDIATRIC CARDIOLOGY Nisco, S. J., Reitz, B. A. 1993; 2 (4): 47-58
  • HYPOTHERMIC PRESERVATION OF THE HEART AND LUNGS WITH COLLINS SOLUTION - EFFECT ON CARDIORESPIRATORY FUNCTION FOLLOWING HEART-LUNG ALLOTRANSPLANTATION IN DOGS ANNALS OF THORACIC SURGERY Feeley, T. W., Mihm, F. G., DOWNING, T. P., Sadeghi, A. M., Baumgartner, W. A., Reitz, B. A., Shumway, N. E. 1986; 41 (3): 301-306

    Abstract

    The effect of preserving the heart and lungs with hypothermia and Collins solution was studied in 13 mongrel dogs undergoing combined heart-lung transplantation. The five control animals who underwent an immediate transplant following Collins solution perfusion had small increases in extravascular lung water when measured 2.5 hours posttransplant as seen in a previous study. The eight animals who had hypothermic preservation following Collins solution perfusion had significantly higher extravascular lung water than controls (16.3 +/- 1.8 ml/kg in preserved animals; 11.2 +/- 1.7 ml/kg in controls p less than 0.05). The level of lung water reached at 2.5 hours postoperatively was similar to that reached with a previously reported, unacceptable preservation technique. Survival beyond this point was poor due to severe pulmonary edema. We conclude that the use of this solution, given under the experimental conditions which we describe, is not acceptable for hypothermic preservation of the heart and lungs for combined transplantation.

    View details for Web of Science ID A1986A544400015

    View details for PubMedID 3082303

  • COMBINED HEART-LUNG TRANSPLANTATION FOR END-STAGE EISENMENGERS SYNDROME JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY McGregor, C. G., Jamieson, S. W., Baldwin, J. C., Burke, C. M., Dawkins, K. D., Stinson, E. B., Oyer, P. E., Billingham, M. E., Zusman, D. R., Reitz, B. A., Yousem, S., Hunt, S. A., Shumway, N. E. 1986; 91 (3): 443-450

    Abstract

    Between May, 1981, and December, 1984, thirteen combined heart-lung transplants were performed in 12 patients for the treatment of Eisenmenger's syndrome. The age range of the recipients was 22 to 42 years. Two patients had undergone previous open cardiac operations; in addition, one had had closure of a persistent ductus arteriosus, one an open lung biopsy, one a pulmonary artery banding, and one patient received a second heart-lung transplant after 3 years. Four recipients died before hospital discharge, one at operation and three at 4, 10, and 33 days after operation. Early symptomatic results and cardiopulmonary function were excellent in all of the survivors. Two patients died 14 and 15 months after transplantation of accelerated graft arteriosclerosis and respiratory failure, respectively, and six remain alive 7 to 44 months after transplantation. Four of these surviving patients and the two patients who died late subsequently had major pulmonary complications. Symptoms included progressive breathlessness, cough (often productive), and fever with physical signs of diffuse crepitations and expiratory rhonchi. Serial pulmonary function tests showed progressive obstructive physiology in all six patients with superimposed restrictive defects in four. Histologic examination of tissue from open lung biopsy or autopsy displayed bronchiolitis obliterans in five of these patients, one of whom required retransplantation. It is possible that these late changes are the result of rejection, since similar changes in one other patient have now been reversed with augmented immunosuppression. Further understanding of the causes and manifestations of late pulmonary deterioration should improve the late functional results of this operation for Eisenmenger's syndrome.

    View details for Web of Science ID A1986A435500016

    View details for PubMedID 3081765

  • SURGICAL REPAIR OF TETRALOGY OF FALLOT - LONG-TERM FOLLOW-UP WITH PARTICULAR EMPHASIS ON LATE DEATH AND REOPERATION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Zhao, H. X., Miller, D. C., Reitz, B. A., Shumway, N. E. 1985; 89 (2): 204-220

    Abstract

    Early and late results in 309 patients undergoing repair of tetralogy of Fallot between 1960 and 1982 were analyzed with respect to independent determinants of operative mortality, late reoperation, and late death. Follow-up extended to 22 years and totaled 2,743 patient-years. The operative mortality rate was 4.9% +/- 1.3%. Multivariate logistic regression analysis revealed that only young age, long cardiopulmonary bypass time, and (probably) extent of right ventricular outflow tract patch were independent significant determinants of operative mortality. Patients who required a transannular right ventricular outflow tract patch and those who underwent repair without any outflow tract patch were at higher risk than those who received a separate right ventricular and/or pulmonary artery patch. The long-term results were highly satisfactory: Only 15% +/- 3% of patients required reoperation 13 years postoperatively, and 85% +/- 4% of discharged patients were alive 16 years later. Time-dependent linear stepwise multivariate discriminant analysis showed that extent of right ventricular outflow tract patch (transannular greater than none greater than right ventricular and/or [separate] pulmonary arterial), longer ischemic arrest time, previous palliative shunt, and primary suture closure of the ventricular septal defect were the only covariates that independently portended a higher likelihood of reoperation. Similarly, only older age, absence of hypoxic spells, and reoperation were significantly and independently related to the probability of late death. The results of these analyses demonstrate that intracardiac repair of tetralogy is a durable procedure for upwards of 20 years; however, high-risk subsets of patients can be identified in terms of operative mortality, reoperation, and late death. Thus, there is still a need for improvement, particularly future research devoted to better understanding of the electrophysiological mechanisms responsible for arrhythmias, electrosurgical and medical arrhythmia therapy, and right and left ventricular mechanics after repair of tetralogy of Fallot.

    View details for Web of Science ID A1985ABW9100006

    View details for PubMedID 3968904

  • LONG-TERM HEMODYNAMICS FOLLOWING COMBINED HEART AND LUNG TRANSPLANTATION IN PRIMATES JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Dawkins, K. D., Haverich, A., Derby, G. C., Scott, W. C., Reitz, B. A., Stinson, E. B., Jamieson, S. W., Shumway, N. E. 1985; 89 (1): 55-62

    Abstract

    To assess the long-term hemodynamic consequences of combined heart and lung transplantation, we investigated six rhesus monkeys 2.6 to 4.6 years (mean 4.0) after operation. Total follow-up was 24.0 primate-years. Autotransplantation had been carried out in four animals and allotransplantation in two, and the hemodynamic results were compared with those in three normal monkeys of similar size. Each animal underwent simultaneous right and left heart catheterization and pulmonary arteriography. Hemodynamic measurements were made at three levels of inspired oxygen. Arterial oxygen tension was within normal limits in all animals, and pulmonary artery pressure and pulmonary vascular resistance index did not change significantly with changes in the levels of inspired oxygen. Indices of left ventricular systolic function were normal in all animals. Values for pulmonary artery pressure and pulmonary vascular resistance index were similar in the autograft and normal groups: in the allograft group, the average pressure was 30/17 mm Hg (mean 24) and the index was 5.6 units . m2--both levels significantly higher than normal (pressure was 16/10 mm Hg, mean 13, [p less than 0.001] and index was 2.5 units . m2 [p less than 0.02]). Pulmonary arteriography in the allograft group with the highest pulmonary vascular resistance index (6.1 units . m2) was compatible with pulmonary vascular disease. Pulmonary arteriograms in the remaining eight monkeys were normal. Prolonged survival following combined heart and lung transplantation is possible in primates. Autotransplantation (and probable persisting denervation of the cardiopulmonary axis) does not necessarily result in abnormal long-term hemodynamics. The elevation in pulmonary artery pressure and pulmonary vascular resistance index in the allograft group may be related to previous episodes of pulmonary rejection, infection, or drug reaction.

    View details for Web of Science ID A1985AAG3900008

    View details for PubMedID 3917517

  • LONG-TERM CARDIAC AND PULMONARY HISTOLOGY IN PRIMATES FOLLOWING COMBINED HEART AND LUNG TRANSPLANTATION TRANSPLANTATION Haverich, A., Dawkins, K. D., Baldwin, J. C., Reitz, B. A., Billingham, M. E., Jamieson, S. W. 1985; 39 (4): 356-360

    Abstract

    To investigate the long-term histologic consequences of combined heart and lung transplantation, heart and lung biopsies were obtained from six rhesus monkeys; two had undergone heart-lung autotransplantation 3.5 and 4.5 years previously, two were the recipients of heart-lung allografts 4.1 and 4.5 years previously, and the results were compared with two normal control animals. Cyclosporine had been used as maintenance immunosuppression in the allograft group. The heart and lung biopsies in the autograft animals were essentially normal. Dense adhesions were noted in the allografts, adn in one the visceral pleura was grossly thickened. Cardiac biopsies in the allografts were unimpressive, with a normal myocardium in one, and minimal interstitial fibrosis in the other. Intimal hyperplasia was present in the pulmonary arterioles of one of the allografted animals. Focal scarring was present in the lung of one allograft recipient, and the other animal showed severe thickening and fibrosis of the alveolar septae, as well as marked interstitial fibrosis such that large areas of the specimen were replaced by connective tissue. Histologic abnormalities in the allografted lungs correlated with the abnormal hemodynamics in these animals reported in a previous study. It is suggested that the histologic appearances in the lung are a consequence of chronic rejection, and that these findings may become a significant problem in human heart-lung transplant recipients.

    View details for Web of Science ID A1985AFP8600003

    View details for PubMedID 3920794

  • THE EFFECT OF HYPOTHERMIC PRESERVATION OF THE HEART AND LUNGS ON CARDIORESPIRATORY FUNCTION FOLLOWING CANINE HEART-LUNG TRANSPLANTATION ANNALS OF THORACIC SURGERY Feeley, T. W., Mihm, F. G., DOWNING, T. P., Sadeghi, A. M., Baumgartner, W. A., Reitz, B. A., Shumway, N. E. 1985; 39 (6): 558-562

    Abstract

    The effect of hypothermic preservation of the heart and lungs with a crystalloid solution was evaluated in 12 mongrel dogs receiving heart-lung allografts. Six animals served as controls and received an immediate heart-lung transplant. Six animals were in the experimental group and received a heart-lung transplant after 5 hours of preservation at 4 degrees C following perfusion of both organs with a crystalloid solution. Physiological function of the heart and lungs was studied for 20 hours after transplantation. While cardiac function was minimally depressed following preservation, pulmonary function testing demonstrated significantly greater increases in extravascular lung water in experimental animals, suggesting that an ischemic lung injury occurred with this preservation technique. The model allows for future evaluation of other methods of combined preservation of both the heart and lungs for transplantation.

    View details for Web of Science ID A1985AJU9100014

    View details for PubMedID 3923955

  • LATE RESULTS OF COMBINED HEART LUNG TRANSPLANTATION TRANSPLANTATION PROCEEDINGS Jamieson, S. W., Dawkins, K. D., Burke, C., Baldwin, J. W., YOUSEUR, S., Billingham, M. E., Hunt, S. A., Reitz, B. A., Theodore, J., Oyer, P. E., Stinson, E. B., Shumway, N. E. 1985; 17 (1): 212-214
  • CYCLOSPORINE IN HEART AND HEART-LUNG TRANSPLANTATION CANADIAN JOURNAL OF SURGERY Modry, D. L., Oyer, P. E., Jamieson, S. W., Stinson, E. B., Baldwin, J. C., Reitz, B. A., Dawkins, K. D., McGregor, C. G., Hunt, S. A., Moran, M., Myers, B., Shumway, N. E. 1985; 28 (3): 274-?

    Abstract

    At Stanford University Medical Center from January 1968 until January 1984, 288 patients received 313 heart transplants. The immunosuppressive regimen before December 1980 consisted of azathioprine and prednisone, with or without rabbit antithymocyte globulin. After that time cyclosporine replaced azathioprine. In 92 recipients of 95 heart allografts, the 1- and 3-year survival rates were 82% and 65% to 70% respectively. In the 3 years from March 1981 to March 1984, successful heart-lung transplantation was accomplished in 13 of 19 recipients, using cyclosporine-based immunosuppression. Survival ranged from 1 to 38 months. While it is true that cyclosporine has improved survival in heart transplant recipients, has allowed successful heart-lung transplantation to be performed, has shortened intensive care unit and total hospital stays and therefore hospital costs, and has allowed easier management of rejection and infection, several disconcerting problems have not yet been resolved. These include hypertension that is difficult to control and renal dysfunction in all patients, and the fact that cellular and humoral rejection still occurs, as manifested by graft atherosclerosis, bronchiolitis obliterans and classic acute rejection. Better understanding and application of cyclosporine immunosuppression will undoubtedly minimize both cyclosporine- and non-cyclosporine-related postoperative complications and will improve survival even further.

    View details for Web of Science ID A1985AHW9000026

    View details for PubMedID 3922606

  • TELEMETRY OF ELECTROPHYSIOLOGIC VARIABLES FROM CONSCIOUS DOGS - SYSTEM-DESIGN, VALIDATION, AND SERIAL STUDIES AMERICAN HEART JOURNAL Rubenson, D., Griffin, J. C., Ford, A., Claude, J., Reitz, B., KNUTTI, J., Billingham, M., HARRISON, D. C. 1984; 107 (1): 90-96

    Abstract

    The necessity for conscious animal models in the study of cardiac physiology has been established for hemodynamics. The characterization of the electrophysiologic properties of the heart has not been performed in a serial fashion in a conscious animal model. Implanted telemetry sensing devices for recording atrial, ventricular, and His electrograms and stimulation systems for both atrium and ventricle allowed serial evaluation of eight dogs for up to 4 months. There were significant fluctuations in some electrophysiologic variables with time, particularly heart rate, sinus node recovery time, and pacing rate for induction of Wenckebach block. This variability did not appear to deviate with time after implantation, and no significant differences in the basal electrophysiologic state were found between the period early after surgery (0 to 2 1/2 weeks) and later (3 to 8 weeks).

    View details for Web of Science ID A1984RZ08700016

    View details for PubMedID 6691246

  • ACUTE PHYSIOLOGICAL-CHANGES FOLLOWING HEART-LUNG ALLOTRANSPLANTATION IN DOGS ANNALS OF THORACIC SURGERY DOWNING, T. P., Sadeghi, A. M., Baumgartner, W. A., Reitz, B. A., Brackup, A., Feeley, T., Mihm, F., Shumway, N. E. 1984; 37 (6): 479-483

    Abstract

    The feasibility of clinical heart-lung transplantation requires a better understanding of the physiological consequences of the operation, heart-lung denervation, and the quality of graft preservation. An acute canine model was used to evaluate heart-lung function during the first 24 hours after transplantation. Measurements of cardiopulmonary dynamics were performed in 5 donor animals and compared sequentially after transplantation in the respective recipients. Orthotopic allotransplantation was performed on cardiopulmonary bypass with moderate hypothermia after perfusion of both the heart and lung with a clinical cardioplegic solution (4 degrees C; potassium chloride, 30 mEq/L; mannitol, 20 gm/L). Postoperatively, the animals were ventilated continuously and anesthetized. Hemodynamic variables were monitored, and measurements were made of arterial and venous oxygen, carbon dioxide, saturation, and pulmonary mechanics. Cardiac output and a derived measurement of lung water were determined. Pulmonary vascular resistance, arteriovenous shunt, resistance, and compliance were calculated. At the termination of the experiment, significant differences were observed between donor and recipient lung-water levels (7.7 +/- 0.9 ml/kg versus 12.0 +/- 3.1 ml/kg, respectively; p less than 0.05); 100% arterial oxygen tension (509 +/- 37 mm/Hg versus 227 +/- 114 mm/Hg, respectively; p less than 0.01); and pulmonary compliance (38 +/- 18 ml/cm H2O versus 11 +/- 4 ml/cm H2O, respectively; p less than 0.05). Arteriovenous shunt increased from 12.2 +/- 4 to 16.5 +/- 5% (p = 0.2). This model evaluates the technique currently employed clinically and will be used in the future to compare methods of heart-lung preservation with the goal of allowing distant heart-lung procurement.

    View details for Web of Science ID A1984SV28100008

    View details for PubMedID 6428335

  • HEART-LUNG TRANSPLANTATION FOR IRREVERSIBLE PULMONARY-HYPERTENSION ANNALS OF THORACIC SURGERY Jamieson, S. W., Stinson, E. B., Oyer, P. E., Reitz, B. A., Baldwin, J., Modry, D., Dawkins, K., Theodore, J., Hunt, S., Shumway, N. E. 1984; 38 (6): 554-562

    Abstract

    Combined heart and lung transplantation was carried out in 17 patients at Stanford University between March, 1981, and December, 1983. The recipients were between 22 and 45 years old. All patients had end-stage pulmonary hypertension; 10 had Eisenmenger's syndrome and the remaining 7, primary pulmonary hypertension. Five patients died within the first few postoperative weeks. The remainder are well between four weeks and 33 months from operation. The immunosuppressive protocol has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin. Azathioprine also was given for the first two weeks and then was replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with high doses of methylprednisolone. Modifications of technique that have developed include the removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution. Rejection occurred in 6 of the 12 survivors. Infections developed in 9 patients, but only one resulted in a fatal outcome (Legionella). Thus, the results of clinical heart-lung transplantation have been considerably superior to clinical efforts in lung transplantation. It is suggested that the combined operation is preferable for the following reasons: (1) all diseased tissue is removed, thus eliminating recurrent infection and ventilation/perfusion disparity; (2) transplantation of the entire heart-lung block preserves coronary-bronchial vascular anastomoses and makes airway dehiscence less likely; and (3) to date, diagnosis of rejection by cardiac biopsy has appeared to be a satisfactory method of diagnosing and treating pulmonary rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1984TW37500004

    View details for PubMedID 6439134

  • PHYSIOLOGIC ASPECTS OF HUMAN HEART-LUNG TRANSPLANTATION - PULMONARY-FUNCTION STATUS OF THE POST-TRANSPLANTED LUNG CHEST Theodore, J., Jamieson, S. W., Burke, C. M., Reitz, B. A., Stinson, E. B., VANKESSEL, A., Dawkins, K. D., Herran, J. J., Oyer, P. E., Hunt, S. A., Shumway, N. E., Robin, E. D. 1984; 86 (3): 349-357

    Abstract

    Pulmonary function measurements were performed before and after heart-lung transplantation in nine patients who had undergone surgery for end-stage pulmonary hypertension. In seven of them, sequential follow-up studies were performed at variable times postoperatively with the longest period 27 months. Pre-transplant studies showed a mild restrictive defect in 33 percent and obstructive disease in 50 percent of the patients, respectively. Arterial hypoxemia was present in all patients. The degree of mechanical changes found did not appear severe enough to account for the marked dyspnea and disability characterizing this group of patients with pulmonary hypertension. Following transplantation, all patients showed striking improvement of symptoms and general physical status. In the early post-transplant period, there was a marked decrease in most lung volumes resulting in a moderately severe restrictive ventilatory defect. Flow parameters that were reduced could be related to decreased volumes and not to intrinsic airway obstruction. Arterial O2 tensions improved dramatically and gas exchange was maintained at essentially normal levels. Lung function tended to improve progressively following transplantation with the passage of time. Heart-lung transplant is consistent with an adequate long-term pulmonary functional state which has the capacity to sustain the normal activities of daily living. From the standpoint of lung function, heart-lung transplantation appears to be acceptable as a form of therapy in selected patients.

    View details for Web of Science ID A1984TG73000007

    View details for PubMedID 6432455

  • CLINICAL HEART-LUNG TRANSPLANTATION TRANSPLANTATION Jamieson, S. W., Baldwin, J., Stinson, E. B., Reitz, B. A., Oyer, P. E., Hunt, S., Billingham, M., Theodore, J., Modry, D., BIEBER, C. P., Shumway, N. E. 1984; 37 (1): 81-84

    Abstract

    Combined heart and lung transplantation was carried out in thirteen patients at Stanford University between March 1981 and May 1983. The recipients were between 22 and 45 years old. All patients were suffering from end-stage pulmonary hypertension; nine patients had Eisenmenger's syndrome; the remaining four were transplanted for primary pulmonary hypertension. Three patients died within one month of surgery. The remainder are well at between 22 months and three weeks from operation. The duration of stay in the hospital for the surviving patients ranged from 38 to 85 days. The immunosuppressive protocol has been essentially the same for all recipients, and has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin (RATG) with azathioprine given for the first two weeks, and then replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with pulses of methylprednisolone. Early complications included bleeding that necessitated reexploration (five patients); damage to the vagus, recurrent laryngeal, or phrenic nerves (three patients); and failure of the donor lungs (one patient). Modifications of technique that have developed include removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution. The results of this operation are considerably superior to clinical efforts in lung transplantation. The combined operation may be preferable for the following reasons: All diseased tissue is removed, thus eliminating recurrent infection, and also perfusion/ventilation disparity. Transplantation of the entire heart and lung block preserves coronary-tracheal vascular anastomoses and makes airway dehiscence less likely. Diagnosis of rejection by cardiac biopsy seems to be a satisfactory method of diagnosis and treatment of pulmonary rejection.

    View details for Web of Science ID A1984RZ82600022

    View details for PubMedID 6420957

  • SURGICAL-TREATMENT OF PROSTHETIC VALVE ENDOCARDITIS ANNALS OF THORACIC SURGERY Baumgartner, W. A., Miller, D. C., Reitz, B. A., Oyer, P. E., Jamieson, S. W., Stinson, E. B., Shumway, N. E. 1983; 35 (1): 87-104

    View details for Web of Science ID A1983PX59600012

    View details for PubMedID 6849584

  • REVASCULARIZATION OF TRACHEAL ANASTOMOSIS FOLLOWING HEART LUNG TRANSPLANTATION INVESTIGATIVE RADIOLOGY GUTHANER, D. F., Wexler, L., Sadeghi, A. M., BLANK, N. E., Reitz, B. A. 1983; 18 (6): 500-503

    Abstract

    The mechanism by which tracheobronchial arterial supply is reconstituted following heart-lung transplantation was investigated in seven monkeys (3 allografts, 2 autografts, and 2 nontransplanted control monkeys) and three patients. Descending tracheal branches of the thyrocervical arteries provided the major tracheal vascular supply. A collateral branch arising from atrial branches of the left coronary artery supplied tracheobronchial branches in the region of the carina in one allograft. In the three patients studied to date by coronary arteriography, a similar collateral supply to the region of the carina and proximal bronchi was demonstrated from atrial branches of both the left and right coronary circulation.

    View details for Web of Science ID A1983RQ66200002

    View details for PubMedID 6417043

  • SIMPLE ADJUNCTS WHICH MAINTAIN SEPTAL TEMPERATURE BELOW 20-DEGREES-C DURING ISCHEMIC ARREST FOR CORONARY-ARTERY BYPASS-GRAFTING AMERICAN HEART JOURNAL Baumgartner, W. A., Miller, D. C., Stinson, E. B., Reitz, B. A., Oyer, P. E., Jamieson, S. W. 1983; 105 (3): 440-444

    View details for Web of Science ID A1983QF05800013

    View details for PubMedID 6338684

  • DIAGNOSIS AND TREATMENT OF ALLOGRAFT-REJECTION IN HEART-LUNG TRANSPLANT RECIPIENTS JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Reitz, B. A., Gaudiani, V. A., Hunt, S. A., Wallwork, J., Billingham, M. E., Oyer, P. E., Baumgartner, W. A., Jamieson, S. W., Stinson, E. B., Shumway, N. E. 1983; 85 (3): 354-361

    Abstract

    Six patients received heart-lung transplants between March, 1981, and January, 1982. There were four women and two men between 26 and 45 years of age, three with primary pulmonary hypertension and three with congenital heart disease and pulmonary hypertension (Eisenmenger's syndrome). Immunosuppression was primarily with cyclosporin-A, with additional corticosteroid, azathioprine, and rabbit antihuman thymocyte globulin. Six episodes of allograft rejection in four patients (10, 11, 21, 24, 53, and 86 days after transplantation) were detected by means of transvenous endomyocardial biopsy. All patients experienced pulmonary edema early after transplantation (reimplantation response), and two patients required mechanical ventilatory support for allograft rejection at 10 and 11 days. Treatment of rejection consisted of intravenous methylprednisolone (four episodes) or augmented oral prednisone (two episodes), with resolution. No episode thought to be pulmonary rejection has occurred in the absence of cardiac findings. Four patients are alive from 6 to 15 months after transplantation and are functionally normal. Early experience with heart-lung transplantation suggests (1) that allograft rejection can be detected by cardiac findings and successfully treated by augmented corticosteroids, (2) that lung rejection does not occur in the absence of cardiac findings, (3) that the frequency and severity of rejection episodes are not greater than with standard cardiac transplantation, and (4) that the frequency of rejection episodes is highest within the first 60 days after transplantation.

    View details for Web of Science ID A1983QG01700005

    View details for PubMedID 6402622

  • COMBINED HEART AND LUNG TRANSPLANTATION LANCET Jamieson, S. W., Baldwin, J., Reitz, B. A., Stinson, E. B., Oyer, P. E., Hunt, S., Billingham, M., Theodore, J., Modry, D., BIEBER, C. P., Shumway, N. E. 1983; 1 (8334): 1130-1132

    Abstract

    Combined heart and lung transplantation was carried out in ten patients at Stanford University Medical Center between March, 1981, and December, 1982. All patients had end-stage pulmonary hypertension. 7 of them had Eisenmenger's syndrome and 3 primary pulmonary hypertension. 3 patients died within a month of operation, but the remaining recipients are well 2 months to 2 years after transplantation. The hospital stay of the survivors ranged from 38 to 85 days. All survivors have returned to normal activity. The results of heart and lung transplantation have thus been considerably superior to those reported previously for lung transplantation. It is suggested that cardiopulmonary replacement is suitable treatment for end-stage pulmonary hypertension with or without associated congenital heart disease and that its application to other forms of advanced pulmonary failure may be warranted.

    View details for Web of Science ID A1983QQ80700005

    View details for PubMedID 6133156

  • CARDIAC ALLOGRAFT SURVIVAL FOLLOWING PRETREATMENT WITH DONOR SPLEEN-CELLS AND CYCLOSPORIN-A TRANSPLANTATION PROCEEDINGS Aziz, S., Oyer, P., Reitz, B., Jamieson, S. W., Bieber, C., Stinson, E. B., Shumway, N. E. 1983; 15 (1): 809-813
  • HEALING AND REVASCULARIZATION OF THE TRACHEAL ANASTOMOSIS FOLLOWING HEART-LUNG TRANSPLANTATION SURGICAL FORUM Sadeghi, A. M., GUTHANER, D. F., Wexler, L., SHOCAT, S. J., DOWNING, T. P., BLANK, N. E., Reitz, B. A. 1982; 33: 236-238
  • MYOCARDIAL PROTECTION DURING CARDIAC-SURGERY ANNUAL REVIEW OF MEDICINE Reitz, B. A. 1982; 33: 151-162

    View details for Web of Science ID A1982NJ65500009

    View details for PubMedID 7081957

  • TEMPERATURE CORRECTION OF PCO2 AND PH IN ESTIMATING ACID-BASE STATUS - AN EXAMPLE OF THE EMPERORS NEW CLOTHES ANESTHESIOLOGY REAM, A. K., Reitz, B. A., Silverberg, G. 1982; 56 (1): 41-44

    View details for Web of Science ID A1982MY12800009

    View details for PubMedID 6797331

  • HYPOTHERMIA AND CARDIAC-ARREST IN THE TREATMENT OF GIANT ANEURYSMS OF THE CEREBRAL-CIRCULATION AND HEMANGIOBLASTOMA OF THE MEDULLA JOURNAL OF NEUROSURGERY Silverberg, G. D., Reitz, B. A., REAM, A. K. 1981; 55 (3): 337-346

    View details for Web of Science ID A1981MC92400002

    View details for PubMedID 7196440

  • ACCEPTANCE OF BONE-MARROW AND ORGAN ALLOGRAFTS AFTER TOTAL LYMPHOID IRRADIATION (TLI) Strober, S., Gottlieb, M. S., King, D. P., KORETZ, S. H., BIEBER, C. P., Reitz, B. A., Hoppe, R. T., KAPLAN, H. S. FEDERATION AMER SOC EXP BIOL. 1980: 1202–
  • OPERATIVE TREATMENT OF A GIANT CEREBRAL-ARTERY ANEURYSM WITH HYPOTHERMIA AND CIRCULATORY ARREST - REPORT OF A CASE NEUROSURGERY Silverberg, G. D., Reitz, B. A., REAM, A. K., Taylor, G., Enzmann, D. R. 1980; 6 (3): 301-305

    Abstract

    A patient with a giant left middle cerebral artery aneurysm is presented. Because of previous operations and dense adhesions of the dominant frontal and temporal lobes to the aneurysm sac, we elected to obliterate the aneurysm by endaneurysmorrhaphy with the patient under hypothermia and cardiac arrest. Elective cardiac arrest has become a relatively safe, controllable procedure and may be of significant value in the treatment of difficult neurosurgical problems.

    View details for Web of Science ID A1980JN05200015

    View details for PubMedID 7383297

  • TRANSPLANTATION TOLERANCE IN ADULT RATS USING TOTAL LYMPHOID IRRADIATION - PERMANENT SURVIVAL OF SKIN, HEART, AND MARROW ALLOGRAFTS JOURNAL OF EXPERIMENTAL MEDICINE Slavin, S., Reitz, B., BIEBER, C. P., KAPLAN, H. S., Strober, S. 1978; 147 (3): 700-707

    Abstract

    Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors. The chimeras showed no clinical signs of graft-versus-host disease. Skin allografts from the marrow donor strain survived for more than 150 days on the chimeras. However, third-party skin grafts were rejected promptly. Although heart allografts survived more than 300 days in Lewis recipients given TLI and bone marrow allografts, detectable levels of chimerism were not required for permanent survival.

    View details for Web of Science ID A1978EQ03200007

    View details for PubMedID 147301

    View details for PubMedCentralID PMC2184184

  • EFFECT OF MAXIMUM EXERCISE AND ATRIAL-PACING ON LEFT-VENTRICULAR VOLUME AND CONTRACTILITY IN INNERVATED AND DENERVATED HUMAN HEARTS McLaughlin, P. R., Kleiman, J. H., Martin, R. P., DOHERTY, P. W., Reitz, B., Stinson, E. B., Daughters, G. T., Ingels, N. B., Alderman, E. L. SLACK INC. 1977: A238–A238
  • FREQUENCY-DEPENDENT CHANGES IN INOTROPIC STATE OF INNERVATED AND DENERVATED HUMAN VENTRICLE Ricci, D. R., ORLICK, A. E., Reitz, B. A., Baumgartner, W. A., Kusnick, C. A., Oyer, P. E., Daughters, G. T., Ingels, N. B., Stinson, E. B., Alderman, E. L. SLACK INC. 1977: A249–A249