- Pediatric Cardiology
- Pediatric Cardiac Intensive Care
Director, The Children's Heart Center, Lucile Packard Children's Hospital, Stanford University (2011 - Present)
Chief, Division of Pediatric Cardiology, Lucile Packard Children's Hospital, Stanford University (2011 - Present)
James Baxter & Yvonne Craig Wood Medical Director, CVICU, Lucile Packard Children's Hospital, Stanford University (2005 - Present)
Honors & Awards
Scholarship for Academic Achievement, Harvard University (1977-1979)
A.B. magna cum laude with High Honors, Harvard University (1980)
M.D. cum laude, Yale University (1986)
Norma Bailey Berniker Prize, Yale University (1986)
New England Pediatric Society Prize, New England Pediatric Society (1986)
Clinical Investigator Development Award, National Institutes of Health (1992-1997)
Faculty Teaching Award, Department of Cardiology, Children's Hospital Boston (1999)
Listed, Best Doctors in America (2001-present)
Medical Education:Yale School Of Medicine Office of Student Affairs (1986) CT
Fellowship:Children's Hospital Boston (1992) MA
Residency:Children's Hospital Boston (1989) MA
Board Certification: Pediatric Cardiology, American Board of Pediatrics (1994)
Internship:Children's Hospital Boston (1987) MA
M.P.H., Harvard School of Public Health, Tropical Public Health (1986)
M.D., Yale University School of Medicine (1986)
Current Research and Scholarly Interests
Randomized Therapeutic Trials in Pediatric Heart Disease, NIH/U01 GrantNo. HL68285 2001-2006.
Heparin and the Reduction of Thrombosis (HART) Study. Pediatric Health Research Fund Award, Stanford Univ Sch of Medicine, 2005-2006.
A Pilot Trial fo B-type Natriuretic Peptide for Promotion of Urine Output in Diuretic-Resistant Infants Following Cardiovascular Surgery.Pediatric Health Research Fund Award, Stanford Univ Sch of Medicine, 2005-2006.
- Independent Studies (5)
- Practice Patterns in Postoperative Echocardiographic Surveillance after Congenital Heart Surgery in Children: A Single Center Experience JOURNAL OF PEDIATRICS 2017; 180: 87-?
Training fellows and residents in paediatric cardiac critical care.
Cardiology in the young
2016; 26 (8): 1531-1536
As pediatric cardiac critical care becomes more sub-specialized it is reasonable to assume that dedicated units may provide a better infrastructure for improved multidisciplinary care, cardiac-specific patient safety initiatives, and dedicated training of fellows and residents. The knowledge base required to optimally manage pediatric patients with critical cardiac disease has evolved sufficiently to consider a standardized training curriculum and board certification for pediatric cardiac critical care. This strategy would potentially provide consistency of training and healthcare and improve quality of care and patient safety.
View details for DOI 10.1017/S1047951116002468
View details for PubMedID 28148334
Silver-Impregnated Dressings for Sternotomy Incisions to Prevent Surgical Site Infections in Children.
American journal of critical care
2016; 25 (5): 402-408
The consequences of surgical site infections can be severe and range from short-term delays in discharge from the hospital to life-threatening infections such as mediastinitis.To evaluate the effectiveness of silver-impregnated dressings in decreasing surgical site infections in children after cardiac surgery.A randomized, controlled trial was used to compare silver-impregnated dressings (59 participants) with standard dressings (58 participants). The study team supervised all dressing changes after a sternotomy and ensured adherence with the hospital's bundle for reduction of surgical site infections. The ASEPSIS tool was used to evaluate sternal wounds for evidence of infection.The 2 groups had comparable Risk Adjustment for Congenital Heart Surgery scores, age, sex, weight, height, operating room characteristics, and number of chest tubes and/or pacemaker wires. No surgical site infections occurred in any study participant. Infections did occur, however, during the same period, in cardiac surgical patients who were not enrolled in the study.The evidence did not support the superiority of silver-impregnated dressings for prevention of surgical site infections in children after cardiac surgery. Adherence to a bundle for prevention of surgical site infections may have decreased the incidence of such infections in the study population during the study period.
View details for DOI 10.4037/ajcc2016843
View details for PubMedID 27587419
Changes in Efficiency and Safety Culture After Integration of an I-PASS-Supported Handoff Process.
2016; 137 (2): 1-9
Recent publications have shown improved outcomes associated with resident-to-resident handoff processes. However, the implementation of similar handoff processes for patients moving between units and teams with expansive responsibilities presents unique challenges. We sought to determine the impact of a multidisciplinary standardized handoff process on efficiency, safety culture, and satisfaction.A prospective improvement initiative to standardize handoffs during patient transitions from the cardiovascular ICU to the acute care unit was implemented in a university-affiliated children's hospital.Time between verbal handoff and patient transfer decreased from baseline (397 ± 167 minutes) to the postintervention period (24 ± 21 minutes) (P < .01). Percentage positive scores for the handoff/transitions domain of a national culture of safety survey improved (39.8% vs 15.2% and 38.8% vs 19.6%; P = .005 and 0.03, respectively). Provider satisfaction improved related to the information conveyed (34% to 41%; P = .03), time to transfer (5% to 34%; P < .01), and overall experience (3% to 24%; P < .01). Family satisfaction improved for several questions, including: "satisfaction with the information conveyed" (42% to 70%; P = .02), "opportunities to ask questions" (46% to 74%; P < .01), and "Acute Care team's knowledgeabout my child's issues" (50% to 73%; P = .04). No differences in rates of readmission, rapid response team calls, or mortality were observed.Implementation of a multidisciplinary I-PASS-supported handoff process for patients transferring from the cardiovascular ICU to the acute care unit resulted in improved transfer efficiency, safety culture scores, and satisfaction of providers and families.
View details for DOI 10.1542/peds.2015-0166
View details for PubMedID 26743818
A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass.
Pediatric critical care medicine
2016; 17 (2): 135-143
Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass.Single-center, double-blinded, placebo-controlled, randomized clinical trial.Tertiary center, pediatric cardiovascular ICU.A total of 144 children after congenital heart surgery with cardiopulmonary bypass.Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours.The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30).In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.
View details for DOI 10.1097/PCC.0000000000000612
View details for PubMedID 26669642
- Exploring Value in Congenital Heart Disease: An Evaluation of Inpatient Admissions CONGENITAL HEART DISEASE 2015; 10 (6): E278-E287
- Task Force 5: Pediatric Cardiology Fellowship Training in Critical Care Cardiology CIRCULATION 2015; 132 (6): E81-E90
- Association of presence and timing of invasive airway placement with outcomes after pediatric in-hospital cardiac arrest RESUSCITATION 2015; 92: 53-58
Utility of Clinical Biomarkers to Predict Central Line-associated Bloodstream Infections After Congenital Heart Surgery.
Pediatric infectious disease journal
2015; 34 (3): 251-254
Central line associated bloodstream infections is an important contributor of morbidity and mortality in children recovering from congenital heart surgery. The reliability of commonly used biomarkers to differentiate these patients have not been specifically studied.This was a retrospective cohort study in a university-affiliated children's hospital examining all patients with congenital or acquired heart disease admitted to the cardiovascular intensive care unit following cardiac surgery who underwent evaluation for a catheter-associated bloodstream infection.Among 1260 cardiac surgeries performed, 451 encounters underwent an infection evaluation post-operatively. Twenty-five instances of CLABSI and 227 instances of a negative infection evaluation were the subject of analysis. Patients with CLABSI tended to be younger (1.34 vs 4.56 years, p = 0.011) and underwent more complex surgery (RACHS-1 score 3.79 vs 3.04, p = 0.039). The two groups were indistinguishable in WBC, PMNs and band count at the time of their presentation. On multivariate analysis, CLABSI was associated with fever (adjusted OR 4.78; 95% CI, 1.6 to 5.8) and elevated CRP (adjusted OR 1.28; 95% CI, 1.09 to 1.68) after adjusting for differences between the two groups. Receiver operating characteristic analysis demonstrated the discriminatory power of both fever and CRP (area under curve 0.7247, 95% CI, 0.42 to 0.74 and 0.58, 95% CI 0.4208 to 0.7408). We calculated multilevel likelihood ratios for a spectrum of temperature and CRP values.We found commonly used serum biomarkers such as fever and CRP not to be helpful discriminators in patients following congenital heart surgery.
View details for DOI 10.1097/INF.0000000000000553
View details for PubMedID 25232780
Incidence, Predictors, and Outcomes of Extubation Failure in Children After Orthotopic Heart Transplantation: A Single-Center Experience
2015; 36 (2): 300-307
The objective of this study is to describe the incidence, etiologies, predictors, and outcomes of extubation failure in children undergoing orthotopic heart transplantation (OHT). A Retrospective, observational study was designed to evaluate clinical outcomes. . The study was conducted in a cardiovascular intensive care unit (CVICU) setting at a single, tertiary care, academic children's hospital. We collected demographic, pre-operative, intra-operative, post-operative and peri-extubation data in a retrospective, observational format from patients who underwent OHT at our institution. Clinical outcomes evaluated included the success or failure of extubation, CVICU length of stay (LOS), hospital LOS, and in-hospital mortality. We utilized descriptive and univariate statistics to compare the group with extubation failure to the group with extubation success. There were no interventions in this study. During the study period, 127 patients qualified for inclusion. The median age of patients was 108 months [interquartile range (IQR): 25-169] and median weight was 23 kg (IQR: 10.6-48). Extubation failure occurred in 12.5 % (16/127) of the patients. Median duration of mechanical ventilation was 2 days (IQR: 1-4.5), median CVICU LOS was 7 days (IQR: 5-13), and the median hospital LOS was 36 days (IQR: 20-74). Overall in-hospital mortality was 2 % (2/127). There was a significant improvement in blood pressure (p < 0.001) with a decrease in inotropic score (p < 0.001) after removal of positive pressure ventilation among the patients with extubation success. Independent factors associated with extubation failure included lower body weight, need for mechanical ventilation prior to heart transplantation, renal failure prior to extubation attempt, and right ventricular diastolic dysfunction prior to extubation attempt. Our study demonstrates that extubation failure in patients after OHT is infrequent and the causes are diverse. Extubation success in children after OHT is associated with improvement in mean arterial blood pressure, decrease in inotropic support, and decrease in supplemental oxygen requirement.
View details for DOI 10.1007/s00246-014-1003-6
View details for Web of Science ID 000348566100009
View details for PubMedID 25135601
Predictors of Mortality in Pediatric Patients on Venoarterial Extracorporeal Membrane Oxygenation
PEDIATRIC CRITICAL CARE MEDICINE
2014; 15 (9): 870-877
Currently, there are no established echocardiographic or hemodynamic predictors of mortality after weaning venoarterial extracorporeal membrane oxygenation in children. We wished to determine which measurements predict mortality.Over 3 years, we prospectively assessed six echo and six hemodynamic variables at 3-5 circuit rates while weaning extracorporeal membrane oxygenation flow. Hemodynamic measurements were heart rate, inotropic score, arteriovenous oxygen difference, pulse pressure, oxygenation index, and lactate. Echo variables included shortening/ejection fraction, outflow tract Doppler-derived stroke distance (velocity-time integral), degree of atrioventricular valve regurgitation, longitudinal strain (global longitudinal strain), and circumferential strain (global circumferential strain).Cardiovascular ICU at Lucille Packard Children's Hospital Stanford, CA.Patients were stratified into those who died or required heart transplant (Gr1) and those who did not (Gr2). For each patient, we compared the change for each variable between full versus minimum extracorporeal membrane oxygenation flow for each group.None.We enrolled 21 patients ranging in age from 0.02 to 15 years. Five had dilated cardiomyopathy, and 16 had structural heart disease with severe ventricular dysfunction. Thirteen of 21 patients (62%) comprised Gr1, including two patients with heart transplants. Eight patients constituted Gr2. Gr1 patients had a significantly greater increase in oxygenation index (35% mean increase; p < 0.01) off extracorporeal membrane oxygenation compared to full flow, but no change in velocity-time integral or arteriovenous oxygen difference. In Gr2, velocity-time integral increased (31% mean increase; p < 0.01), with no change in arteriovenous oxygen difference or oxygenation index. Pulse pressure increased modestly with flow reduction only in Gr1 (p < 0.01).Failure to augment velocity-time integral or an increase in oxygenation index during the extracorporeal membrane oxygenation weaning is associated with poor outcomes in children. We propose that these measurements should be performed during extracorporeal membrane oxygenation wean, as they may discriminate who will require alternative methods of circulatory support for survival.
View details for DOI 10.1097/PCC.0000000000000236
View details for Web of Science ID 000346400100015
View details for PubMedID 25230312
- Reperfusion pulmonary edema in children with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries undergoing unifocalization procedures: A pilot study examining potential pathophysiologic mechanisms and clinical significance JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2014; 148 (4): 1560-1565
- Outcomes Following Cardiac Catheterization After Congenital Heart Surgery CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 2014; 84 (4): 622-628
Sedative and analgesic use on night and day shifts in a pediatric cardiovascular intensive care unit.
AACN advanced critical care
2014; 25 (2): 114-118
The use of sedative and analgesic medications is directly linked to patient outcomes. The practice of administering as-needed sedative or analgesic medications deserves further exploration. We hypothesized that important variations exist in the practice of administering as-needed medications in the intensive care unit (ICU). We aimed to determine the influence of time of day on the practice of administering as-needed sedative or analgesic medications to children in the ICU.Medication administration records of patients admitted to our pediatric cardiovascular ICU during a 4-month period were reviewed to determine the frequency and timing of as-needed medication usage by shift.A total of 152 ICU admissions (1854 patient days) were reviewed. A significantly greater number of as-needed doses were administered during the night shift (fentanyl, P = .005; lorazepam, P = .03; midazolam, P = .0003; diphenhydramine, P = .0003; and chloral hydrate, P = .0006). These differences remained statistically significant after excluding doses given during the first 6 hours after cardiovascular surgery. Morphine administration was similar between shifts (P = .08).We identified a pattern of increased administration of as-needed sedative or analgesic medications during nights. Further research is needed to identify the underlying causes of this practice variation.
View details for DOI 10.1097/NCI.0000000000000023
View details for PubMedID 24752023
- Variability of Characteristics and Outcomes Following Cardiopulmonary Resuscitation Events in Diverse ICU Settings in a Single, Tertiary Care Children's Hospital*. Pediatric critical care medicine 2014; 15 (3): e128-41
Initial Experience Using Aminophylline to Improve Renal Dysfunction in the Pediatric Cardiovascular ICU
PEDIATRIC CRITICAL CARE MEDICINE
2014; 15 (1): 21-27
To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU.Single-center retrospective cohort study.Pediatric cardiovascular ICU, university-affiliated children's hospital.Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload.Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload.Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration.Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.
View details for DOI 10.1097/01.pcc.0000436473.12082.2f
View details for Web of Science ID 000329368400007
View details for PubMedID 24212284
One hundred useful references in pediatric cardiac intensive care: the 2012 update.
Pediatric critical care medicine
2013; 14 (8): 770-785
The specialty of pediatric cardiac critical care has undergone rapid scientific and clinical growth in the last 25 years. The Board of Directors of the Pediatric Cardiac Intensive Care Society assembled an updated list of sentinel references focused on the critical care of children with congenital and acquired heart disease. We encouraged board members to select articles that have influenced and informed their current practice or helped to establish the standard of care. The objective of this article is to provide clinicians with a compilation and brief summary of these updated 100 useful references.The list of 'One Hundred Useful References for Pediatric Cardiac Intensive Care' (2004) and relevant literature to the practice of cardiac intensive care.A subset of Pediatric Cardiac Intensive Care Society board members compiled the initial list of useful references in 2004, which served as the basis of the new updated list. Suggestions for relevant articles were submitted by the Pediatric Cardiac Intensive Care Society board members and selected pediatric cardiac intensivists with an interest in this project following the Society's meeting in 2010. Articles were considered for inclusion if they were named in the original list from 2004 or were suggested by Pediatric Cardiac Intensive Care Society board members and published before December 31, 2011.Following submission of the complete list by the Pediatric Cardiac Intensive Care Society board and contributing Society members, articles were complied by the two co-first authors (D.A., D.K.). The authors also performed Medline searches to ensure comprehensive inclusion of all relevant articles. The final list was then submitted to the Pediatric Cardiac Intensive Care Society board members, who ranked each publication.Rankings were compiled and the top 100 articles with the highest scores were selected for inclusion in this publication. The two co-first authors (D.A., D.K.) reviewed all existing summaries and developed summaries of the newly submitted articles.An updated compilation of 100 useful references for the critical care of children with congenital and acquired heart disease has been compiled and summarized here. Clinicians and trainees may wish to use this document as a reference for education in this complex and challenging subspecialty.
View details for DOI 10.1097/01.PCC.0000434621.25332.71
View details for PubMedID 24088673
Clinical outcome score predicts the need for neurodevelopmental intervention after infant heart surgery
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2013; 145 (5): 1248-?
Our goal was to determine if a clinical outcome score derived from early postoperative events is associated with 18- to 24-month Psychomotor Developmental Index (PDI) score among infants undergoing cardiopulmonary bypass surgery.We included infants aged ≤6 weeks who underwent surgery during 2002-2006, all of whom were referred for neurodevelopmental evaluation at age 18 to 24 months. We excluded children with chromosomal abnormalities, hearing loss, cerebral palsy, or a Bayley III assessment. The prespecified clinical outcome score had a range of 0 to 7. Lower scores indicated a more rapid postoperative recovery. Patients requiring extracorporeal membrane oxygenation were assigned a score of 7.Ninety-nine subjects were included. Surgical procedures were arterial switch (n = 36), Norwood (n = 26), repair of total anomalous pulmonary venous connection (n = 16), and other (n = 21). Four subjects had postoperative extracorporeal membrane oxygenation. Clinical outcome scores were highest in the Norwood group (mean 4.1 ± 1.4) compared with the arterial switch group (1.9 ± 1.6) (P < .001), total anomalous pulmonary venous connection group (1.6 ± 2.0) (P < .001), and other group (3.3 ± 1.6, P = not significant). A mean decrease in PDI of 10.9 points (95% confidence interval, 4.9-16.9; P = .0005) was observed among children who had a clinical outcome score ≥3, compared with those with a clinical outcome score <3. Time until lactate ≤2.0 mmol/L increased with increasing clinical outcome score (P = .0003), as did highest 24-hour inotrope score (P < .0001).Clinical outcome scores of ≥3 were associated with a significantly lower PDI at age 18 to 24 months. This score may be valuable as an end point when evaluating novel potential therapies for this high-risk population.
View details for DOI 10.1016/j.jtcvs.2012.04.029
View details for Web of Science ID 000317840600018
View details for PubMedID 22959319
Postoperative respiratory failure in children with tetralogy of fallot, pulmonary atresia, and major aortopulmonary collaterals: a pilot study.
Pediatric critical care medicine
2013; 14 (4): 384-389
: Children with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collaterals (TOF/PA/MAPCAs), who undergo unifocalization surgery are at risk for prolonged postoperative respiratory failure. We sought to identify risk factors that are associated with prolonged mechanical ventilation in this population.: We collected preoperative and operative data from medical records and postoperative data prospectively. Mechanical ventilation beyond postoperative day 5, which was greater than the 50th percentile for the subjects enrolled, was considered prolonged. Risk factors were analyzed using multiple logistic regression, independent samples t test, Fisher's exact test, and Kruskal-Wallis test. Enrollment occurred over a 20-month period between May 2009 and January 2011.: Lucile Packard Children's Hospital (Palo Alto, CA).: All patients with TOF/PA/MAPCAs presenting for unifocalization or pulmonary artery revision procedures were eligible, including those with additional structural cardiac abnormalities requiring surgical intervention. We excluded patients with single-ventricle cardiac anatomy and preoperative respiratory failure or infection.: We enrolled 35 consecutive patients undergoing 37 procedures over the study period. One patient was excluded for single-ventricle anatomy. There were 12 cases (32%) of prolonged mechanical ventilation. Delayed sternal closure was the only risk factor associated with prolonged mechanical ventilation (p = 0.01). Age, weight, cardiopulmonary bypass time, 22q11 microdeletion, postoperative fluid balance, bronchospasm, and nonrespiratory infection were not significantly associated with prolonged mechanical ventilation. Respiratory complications occurred in both groups, and patients with pneumonia were more likely to have a prolonged course (p = 0.03). There was no significant association between the type of surgery performed and duration of mechanical ventilation.: Prolonged postoperative respiratory failure in children undergoing surgery for TOF/PA/MAPCAs was independently associated with delayed sternal closure. Respiratory complications occur after unifocalization surgery, and pneumonia is associated with prolonged mechanical ventilation. Our pilot study suggests that clinical features common in this patient population, such as bronchospasm and 22q11 microdeletion, were not associated with more postoperative respiratory failure.
View details for DOI 10.1097/PCC.0b013e318272062b
View details for PubMedID 23439458
Efficacy and Predictors of Success of Noninvasive Ventilation for Prevention of Extubation Failure in Critically Ill Children With Heart Disease
2013; 34 (4): 964-977
The study aimed primarily to evaluate the efficacy of noninvasive ventilation (NIV) and to identify possible predictors for success of NIV therapy in preventing extubation failure in critically ill children with heart disease. The secondary objectives of this study were to assess the efficacy of prophylactic NIV therapy initiated immediately after tracheal extubation and to determine the characteristics, outcomes, and complications associated with NIV therapy in pediatric cardiac patients. A retrospective review examined the medical records of all children between the ages 1 day and 18 years who sustained acute respiratory failure (ARF) that required NIV in the cardiovascular intensive care unit (CVICU) at Lucile Packard Children's Hospital between January 2008 and June 2010. Patients were assigned to a prophylactic group if NIV was started directly after extubation and to a nonprophylactic group if NIV was started after signs and symptoms of ARF developed. Patients were designated as responders if they received NIV and did not require reintubation during their CVICU stay and nonresponders if they failed NIV and reintubation was performed. The data collected included demographic data, preexisting conditions, pre-event characteristics, event characteristics, and outcome data. The outcome data evaluated included success or failure of NIV, duration of NIV, CVICU length of stay (LOS), hospital LOS, and hospital mortality. The two complications of NIV assessed in the study included nasal bridge or forehead skin necrosis and pneumothorax. The 221 eligible events during the study period involved 172 responders (77.8 %) and 49 nonresponders (22.2 %). A total of 201 events experienced by the study cohort received continuous positive airway pressure (CPAP), with 156 responders (78 %), whereas 20 events received bilevel positive airway pressure (BiPAP), with 16 responders (80 %). In the study, 58 events (26.3 %) were assigned to the prophylactic group and 163 events (73.7 %) to the nonprophylactic group. Compared with the nonprophylactic group, the prophylactic group experienced significantly shorter CVICU LOS (median, 49 vs 88 days; p = 0.03) and hospital LOS (median, 60 vs 103 days; p = 0.05). The CVICU LOS and hospital LOS did not differ significantly between the responders (p = 0.56) and nonresponders (p = 0.88). Significant variables identifying a responder included a lower risk-adjusted classification for congenital heart surgery (RACHS-1) score (1-3), a good left ventricular ejection fraction, a normal respiratory rate (RR), normal or appropriate oxygen saturation, prophylactic or therapeutic glucocorticoid therapy within 24 h of NIV initiation, presence of atelectasis, fewer than two organ system dysfunctions, fewer days of intubation before extubation, no clinical or microbiologic evidence of sepsis, and no history of reactive airway disease. As a well-tolerated therapy, NIV can be safely and successfully applied in critically ill children with cardiac disease to prevent extubation failure. The independent predictors of NIV success include lower RACHS-1 classification, presence of atelectasis, steroid therapy received within 24 h after NIV, and normal heart rate and oxygen saturations demonstrated within 24 h after initiation of NIV.
View details for DOI 10.1007/s00246-012-0590-3
View details for Web of Science ID 000316957900028
View details for PubMedID 23196891
PREDICTORS OF MORTALITY IN PEDIATRIC PATIENTS ON VENOUS-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION
62nd Annual Scientific Session of the American-College-of-Cardiology
ELSEVIER SCIENCE INC. 2013: E436–E436
View details for Web of Science ID 000316555200436
Pediatric plastic bronchitis: case report and retrospective comparative analysis of epidemiology and pathology.
Case reports in pulmonology
2013; 2013: 649365-?
Plastic bronchitis (PB) is a pathologic condition in which airway casts develop in the tracheobronchial tree causing airway obstruction. There is no standard treatment strategy for this uncommon condition. We report an index patient treated using an emerging multimodal strategy of directly instilled and inhaled tissue plasminogen activator (t-PA) as well as 13 other cases of PB at our institution between 2000 and 2012. The majority of cases (n = 8) occurred in patients with congenital heart disease. Clinical presentations, treatments used, histopathology of the casts, and patient outcomes are reviewed. Further discussion is focused on the epidemiology of plastic bronchitis and a systematic approach to the histologic classification of casts. Comorbid conditions identified in this study included congenital heart disease (8), pneumonia (3), and asthma (2). Our institutional prevalence rate was 6.8 per 100,000 patients, and our case fatality rate was 7%.
View details for DOI 10.1155/2013/649365
View details for PubMedID 23662235
View details for PubMedCentralID PMC3639666
Safety and efficacy of prolonged dexmedetomidine use in critically ill children with heart disease
PEDIATRIC CRITICAL CARE MEDICINE
2012; 13 (6): 660-666
To evaluate the safety and efficacy of prolonged dexmedetomidine administration (≥ 96 hrs) in critically ill children with heart disease.Retrospective observational study.Cardiovascular intensive care unit in a single, tertiary care, academic children's hospital.None.We conducted a retrospective review of the charts of all critically ill infants and children (up to 18 yrs of age) with congenital or acquired heart disease who received dexmedetomidine for ≥ 96 hrs in our pediatric cardiovascular intensive care unit between January 2009 and March 2010. Patients were divided into two groups for study purposes: the dexmedetomidine group (n = 52) included patients who received a dexmedetomidine infusion along with other conventional sedation agents, and the control group (n = 42) included patients who received conventional sedation agents without the use of dexmedetomidine. Clinical outcomes evaluated in our study included days of mechanical ventilation, cardiovascular intensive care unit length of stay, hospital length of stay, and mortality. To evaluate the safety of dexmedetomidine, we collected physiologic data, including heart rate, mean arterial pressure, respiratory rate, systemic oxygen saturation by pulse oximetry, and inotrope score. To assess the efficacy of dexmedetomidine, we examined the amount and duration of concomitant sedation and analgesic infusions over a period of 24 hrs in both dexmedetomidine and control groups. We also examined the number of rescue boluses for each category prior to the initiation of sedative infusion, during the sedative infusion, and after the termination of the sedative infusion. The potential side effects evaluated in our study included nausea, vomiting, abdominal distension, dysrhythmias, neurological abnormalities, seizures, and signs and symptoms of withdrawal.Patients' baseline characteristics were similar in the two groups. Patient complexity as measured by Risk-Adjusted Classification for Congenital Heart Surgery-1 score, ventricular ejection fraction, and proportion of patients receiving mechanical ventilatory support at the time of initiation of sedative infusion was also similar. The duration and amount of continuous midazolam and morphine infusions were significantly lower in the dexmedetomidine group when compared to the control group. During dexmedetomidine infusion, there was no statistical difference in the heart rate and blood pressure between the two groups. Inotrope score was significantly lower in the dexmedetomidine group as compared to the control group in the last 6 hrs prior to termination of dexmedetomidine infusion (p < .001), and at 1 hr (p < .001) and 6 hrs (p < .001) after termination of dexmedetomidine infusion. There was no difference in duration of mechanical ventilation (p = .77), cardiovascular intensive care unit length of stay (p = .29), or hospital length of stay (p = .43) in the two groups. One patient experienced junctional rhythm at 130 beats/min requiring temporary pacing. No other significant side effects were noted. A higher proportion of patients in the dexmedetomidine group were administered clonidine when compared to the control group after termination of dexmedetomidine (31% vs. 7%, p = .005).Prolonged dexmedetomidine administration in children with heart disease appears to be safe and is associated with decreased opioid and benzodiazepine requirement and decreased inotropic support.
View details for DOI 10.1097/PCC.0b013e318253c7f1
View details for Web of Science ID 000310795100015
View details for PubMedID 22791093
Early Outcomes After Extracardiac Conduit Fontan Operation Without Cardiopulmonary Bypass
2012; 33 (7): 1078-1085
Cardiopulmonary bypass is associated with a systemic inflammatory response. The authors hypothesized that avoiding cardiopulmonary bypass would lead to improved postoperative outcomes for patients undergoing the extracardiac Fontan operation, the final stage in surgical palliation of univentricular congenital heart defects. A review of the Children's Heart Center Database showed a total of 73 patients who underwent an initial Fontan operation at Lucile Packard Children's Hospital at Stanford between 1 November 2001 and 1 November 2006. These patients were divided into two groups: those who underwent cardiopulmonary bypass (n = 26) and those who avoided cardiopulmonary bypass (n = 47). Preoperative demographics, hemodynamics, and early postoperative outcomes were analyzed. The two groups had comparable preoperative demographic characteristics and hemodynamics except that the average weight of the off-bypass group was greater (17.9 ± 9.1 vs 14.2 ± 2.7 kg; P = 0.01). Intraoperatively, the off-bypass group trended toward a lower rate of Fontan fenestration (4.3 vs 19.2%; P = 0.09), had lower common atrial pressures (4.6 ± 1.4 vs 5.5 ± 1.5 mmHg; P = 0.05), and Fontan pressures (11.9 ± 2.1 vs 14.2 ± 2.4 mmHg; P ≤ 0.01), and required less blood product (59.1 ± 37.6 vs 91.9 ± 49.4 ml/kg; P ≤ 0.01). Postoperatively, there were no significant differences in hemodynamic parameters, postoperative colloid requirements, duration of mechanical ventilation, volume or duration of pleural drainage, or duration of cardiovascular intensive care unit or hospital stay. Avoiding cardiopulmonary bypass influenced intraoperative hemodynamics and the incidence of fenestration but did not have a significant impact on the early postoperative outcomes of children undergoing the Fontan procedure.
View details for DOI 10.1007/s00246-012-0228-5
View details for Web of Science ID 000308828200011
View details for PubMedID 22349678
Predictors for use of temporary epicardial pacing wires after pediatric cardiac surgery
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2012; 144 (3): 557-562
The objectives of this study were (1) to determine the use of temporary epicardial pacing wires to diagnose and treat early postoperative arrhythmias in pediatric cardiac surgical patients and (2) to determine the predictive factors for the need of pacing wires for diagnostic or therapeutic purposes.We collected preoperative, intraoperative, and postoperative data in a prospective, observational format from patients undergoing pediatric cardiac surgery between August 2010 and January 2011 at a single academic children's hospital.A total of 157 patients met the inclusion criteria during the study period. Of these 157 patients, pacing wires were placed in 127 (81%). Pacing wires were used in 25 patients (19.6%) for diagnostic purposes, 26 patients (20.4%) for therapeutic purposes, 15 patients (11.8%) for both diagnostic and therapeutic purposes, and 36 patients (28.3%) for diagnostic or therapeutic purposes. Need for cardioversion in the operating room, presence of 2 or more intracardiac catheters, severely reduced ventricular ejection fraction, and elevated serum lactate level at the time of operating room discharge were found to be independent predictors for the use of pacing wires. The only complication noted in the cohort was a skin infection at a pacing wire insertion site in 1 patient. A permanent pacemaker was required in 8 (6.2%) of all patients with temporary pacing wires.Our data support the use of temporary epicardial pacing wires in approximately 30% of children after congenital heart surgery. We found the need for cardioversion in the operating room, presence of 2 or more intracardiac catheters, severely reduced ventricular ejection fraction, and high serum lactate level at the time of discharge from the operating room to be independent predictors of the use of pacing wires in the early postoperative period.
View details for DOI 10.1016/j.jtcvs.2011.12.060
View details for Web of Science ID 000308064200037
View details for PubMedID 22329984
Pulmonary reperfusion injury after the unifocalization procedure for tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2012; 144 (1): 184-189
The aims of our study are to describe the incidence, clinical profile, and risk factors for pulmonary reperfusion injury after the unifocalization procedure for tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries. We hypothesized the following: (1) Pulmonary reperfusion injury is more likely to occur after unifocalization procedures in which a septated circulation is not achieved, (2) pulmonary reperfusion injury is directly related to the severity of stenosis in major aortopulmonary collateral arteries, and (3) pulmonary reperfusion injury leads to longer intubation time and longer hospitalization.Consecutive patients with tetralogy of Fallot/pulmonary atresia/major aortopulmonary collateral arteries who underwent unifocalization procedures over a 5-year period were identified in our institutional database. Chest radiographs before the unifocalization procedure, from postoperative days 0 to 4, and from 2 weeks after the unifocalization procedure or at discharge were evaluated by a pediatric radiologist for localized pulmonary edema. Determination of stenosis severity was based on review of preoperative angiograms. Statistical analyses using multivariate repeated-measures analyses were performed with generalized estimating equations.Pulmonary reperfusion injury was present after 42 of 65 (65%) unifocalization procedures. In 36 of 42 cases of reperfusion injury, unilateral injury was present. Risk factors for the development of reperfusion injury included bilateral unifocalization (P = .01) and degree of stenosis (P = .03). We did not identify an association between pulmonary reperfusion injury and time to tracheal extubation or hospital discharge.Pulmonary reperfusion injury is common after the unifocalization procedure for tetralogy of Fallot/pulmonary atresia/major aortopulmonary collateral arteries. Severity of stenosis and bilateral unifocalization are associated with the development of reperfusion injury.
View details for DOI 10.1016/j.jtcvs.2011.12.030
View details for Web of Science ID 000305412200031
View details for PubMedID 22244564
Nursing mortality and morbidity and journal club cycles: paving the way for nursing autonomy, patient safety, and evidence-based practice.
AACN advanced critical care
2012; 23 (2): 133-141
The ability to perform professional scrutiny is a required component of autonomous practice, and the ability to use science to guide care delivery is a hallmark of professional practice. The cardiovascular intensive care unit staff initiated a forum for peer review to encourage the use of the best available evidence to guide system and practice changes. A focus group was formed, resulting in development and implementation of a specific process for regular cycles of nursing mortality and morbidity (M & M) conferences, a journal club, and interdisciplinary educational sessions in staff meetings. After performing several cycles, the team observed interdisciplinary practice changes that improved patient care delivery. Thus, cycles of nursing M & M conferences, a journal club, and educational sessions can help support patient safety, enhance professional autonomy, and foster evidence-based interdisciplinary practice in the cardiovascular intensive care setting.
View details for DOI 10.1097/NCI.0b013e3182424ce7
View details for PubMedID 22543486
- Rapid Response Team Implementation in a Children's Hospital ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE 2011; 165 (12): 1139-1139
Hemodynamic correlates of serum cortisol in neonates after cardiopulmonary bypass
PEDIATRIC CRITICAL CARE MEDICINE
2011; 12 (3): 297-303
To document preoperative and early postoperative serum cortisol levels among a group of neonates with complex congenital heart disease undergoing cardiopulmonary bypass surgery and to describe the relationship between serum cortisol and hemodynamic variables in the early postoperative period.Prospective observational substudy conducted within a randomized controlled trial.Tertiary-care pediatric cardiac intensive care unit.: We consecutively enrolled neonates undergoing a modified Norwood procedure or repair of interrupted aortic arch with ventricular septal defect in a randomized, placebo-controlled trial of triiodothyronine replacement. Methylprednisolone (30 mg/kg intravenously) was administered at anesthetic induction.We measured serum cortisol preoperatively and at 24 and 48 hrs postoperatively. Atrial filling pressures were documented 24 and 48 hrs after surgery. Oxygen consumption was measured and cardiac index was calculated 48 hrs after surgery. Spearman's correlation and linear regression were used to examine the relationship between serum cortisol and postoperative variables. Thirty-eight patients met eligibility criteria. Median serum cortisol levels 24 and 48 hrs postoperatively were 5.0 μg/dL (range 0.4-74.0) and 4.0 μg/dL (range 0.3-17.0), respectively (p = not significant). Greater atrial filling pressures were correlated with higher serum cortisol levels 24 hrs (r = .42, p = .019) and 48 hrs (r = .46, p = .022) after surgery. A lower cardiac index was correlated with higher serum cortisol levels 48 hrs postoperatively (r = -.49, p = .039), and this relationship remained significant after controlling for inotrope score, treatment with triiodothyronine, and atrial filling pressure in bivariate models. Systolic and diastolic BP did not correlate with serum cortisol at 24 or 48 hrs.Serum cortisol levels were low in the majority of subjects, although a wide range was observed. Higher cortisol levels were associated with greater atrial filling pressures and a lower cardiac index. The relationship between serum cortisol and cardiovascular performance after cardiopulmonary bypass in infants warrants further evaluation.
View details for DOI 10.1097/PCC.0b013e3181f36929
View details for Web of Science ID 000290248500018
View details for PubMedID 20921922
Survival after extreme left atrial hypertension and pulmonary hemorrhage in an infant supported with extracorporeal membrane oxygenation for refractory atrial flutter
PEDIATRIC CRITICAL CARE MEDICINE
2011; 12 (3): E149-E152
We report here the survival of an infant who developed extreme left atrial hypertension and severe pulmonary hemorrhage while supported with extracorporeal membrane oxygenation for refractory atrial flutter. The patient recovered after decompression of the left heart and catheter ablation of the atrioventricular node.Lucile Packard Children's Hospital (Stanford, CA).Chart review.Recovery of lung function is possible despite systemic-level left atrial pressure resulting in pulmonary hemorrhage and complete solidification of lung parenchyma on gross inspection. Resolution of pulmonary hemorrhage despite anticoagulation while on extracorporeal membrane oxygenation can occur after relief of left atrial hypertension.
View details for DOI 10.1097/PCC.0b013e3181e8b3e5
View details for Web of Science ID 000290248500008
View details for PubMedID 20693934
Implementation of a Comprehensive Interdisciplinary Care Coordination of Infants and Young Children on Berlin Heart Ventricular Assist Devices
JOURNAL OF CARDIOVASCULAR NURSING
2011; 26 (3): 231-238
Young children supported on a ventricular assist device (VAD) can have prolonged hospitalizations awaiting heart transplantation. The adult VAD literature demonstrates that comprehensive programs optimize transplantation outcomes. The goal of this intervention was to create an interdisciplinary program to optimize care coordination and delivery in young children requiring a VAD.This study was a case review.We have supported 8 infants and young children with Berlin Heart VAD. These children's hospitalizations have been more complex than those of our older VAD patients, and they have required intensive care for prolonged periods. An interdisciplinary group evaluated our practices and identified areas for potential improvement. The focus group from our intensive care unit introduced multiple interventions to optimize interdisciplinary care coordination and consistency of practice. These included (1) interdisciplinary care guidelines for chronically, critically ill patients; (2) institution of a primary cardiovascular intensive care unit (CVICU) physician and nurse practitioner system; (3) introduction of a psychological intervention for families to minimize the impact of their extended CVICU stay; (4) implementation of early jejunal feeds; (5) a focused developmental and rehabilitation protocol, 6) implementation of a structured approach to minimizing blood transfusions; (7) increased structure for our interdisciplinary rounds to optimize team communication; (8) comprehensive nursing education including wound care, anticoagulation management, and laboratory draws; and (9) a protocol for off-unit rehabilitative/developmental interventions. These changes in both practice and approach for young VAD patients have also been of benefit to other chronically, critically ill children in the CVICU, as well as to our CVICU team.Comprehensive interdisciplinary care coordination and standardized practice can be achieved in the critical care setting for complex pediatric heart failure patients who require long-term VAD support.
View details for DOI 10.1097/JCN.0b013e3181f29a2e
View details for Web of Science ID 000289404100010
View details for PubMedID 21099697
PULMONARY REPERFUSION INJURY AFTER THE UNIFOCALIZATION PROCEDURE FOR TETRALOGY OF FALLOT, PULMONARY ATRESIA AND MAJOR AORTOPULMONARY COLLATERAL ARTERIES
60th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) / I2 Summit / ACCF/Herman K. Gold Young Investigator's Award in Molecular and Cellular Cardiology
ELSEVIER SCIENCE INC. 2011: E419–E419
View details for Web of Science ID 000291695100420
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
2010; 3 (6): 682-688
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
A continuous heparin infusion does not prevent catheter-related thrombosis in infants after cardiac surgery
PEDIATRIC CRITICAL CARE MEDICINE
2010; 11 (4): 489-495
To determine whether a continuous infusion of heparin reduces the rate of catheter-related thrombosis in neonates and infants post cardiac surgery. Central venous and intracardiac catheters are used routinely in postoperative pediatric cardiac patients. Catheter-related thrombosis occurs in 8% to 45% of pediatric patients with central venous catheters.Single-center, randomized, placebo-controlled, double-blinded trial.Cardiovascular intensive care unit, university-affiliated children's hospital.Children <1 yr of age recovering from cardiac surgery.Patients were randomized to receive either continuous heparin at 10 units/kg/hr or placebo. The primary end point was catheter-related thrombosis as assessed by serial ultrasonography.Study enrollment was discontinued early based on results from an interim futility analysis. Ninety subjects were enrolled and received the study drug (heparin, 53; placebo, 37). The catheter-related thrombosis rate in the heparin group, compared with the placebo group, was 15% vs. 16% (p = .89). Subjects in the heparin group had a higher mean partial thromboplastin time (52 secs vs. 42 secs, p = .001), and this difference was greater for those aged <30 days (64 secs vs. 43 secs, p = .008). Catheters in place > or = 7 days had both a greater risk of thrombus formation (odds ratio, 4.3; p = .02) and catheter malfunction (odds ratio, 11.2; p = .008). We observed no significant differences in other outcome measures or in the frequency of adverse events.A continuous infusion of heparin at 10 units/kg/hr was safe but did not reduce catheter-related thrombus formation. Heparin at this dose caused an increase in partial thromboplastin time values, which, unexpectedly, was more pronounced in neonates.
View details for DOI 10.1097/PCC.0b013e3181ce6e29
View details for Web of Science ID 000279641500008
View details for PubMedID 20101197
- Host Factor Vulnerability and Development of Progressive Intraluminal Pulmonary Vein Stenosis after Congenital Heart Surgery CONGENITAL HEART DISEASE 2009; 4 (2): 86-90
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
ELSEVIER SCIENCE INC. 2009: S207–S208
View details for Web of Science ID 000263539800406
Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2008; 135 (2): 347-U97
We previously reported that postoperative hemodynamics and developmental outcomes were better among infants randomized to a higher hematocrit value during hypothermic cardiopulmonary bypass. However, worse outcomes were concentrated in patients with hematocrit values of 20% or below, and the benefits of hematocrit values higher than 25% were uncertain.We compared perioperative hemodynamics and, at 1 year, developmental outcome and brain magnetic resonance imaging in a single-center, randomized trial of hemodilution to a hematocrit value of 25% versus 35% during hypothermic radiopulmonary bypass for reparative heart surgery in infants undergoing 2-ventricle repairs without aortic arch obstruction.Among 124 subjects, 56 were assigned to the lower-hematocrit strategy (24.8% +/- 3.1%, mean +/- SD) and 68 to the higher-hematocrit strategy (32.6% +/- 3.5%). Infants randomized to the 25% strategy, compared with the 35% strategy, had a more positive intraoperative fluid balance (P = .007) and lower regional cerebral oxygen saturation at 10 minutes after cooling (P = .04) and onset of low flow (P = .03). Infants with dextro-transposition of the great arteries in the 25% group had significantly longer hospital stay. Other postoperative outcomes, blood product usage, and adverse events were similar in the treatment groups. At age 1 year (n = 106), the treatment groups had similar scores on the Psychomotor and Mental Development Indexes of the Bayley Scales; both groups scored significantly worse than population norms.Hemodilution to hematocrit levels of 35% compared with those of 25% had no major benefits or risks overall among infants undergoing 2-ventricle repair. Developmental outcomes at age 1 year in both randomized groups were below those in the normative population.
View details for DOI 10.1016/j.jtcvs.2007.01.051
View details for Web of Science ID 000252830400017
View details for PubMedID 18242267
- Response to Frost P and Wise MP: Cardiorespiratory Arrests and Rapid Response Teams in Pediatrics Journal of the American Medical Association 2008; 299: 1423-1424
Effect of a rapid response team on hospital-wide mortality and code rates outside the ICU in a children's hospital
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
2007; 298 (19): 2267-2274
Introduction of a rapid response team (RRT) has been shown to decrease mortality and cardiopulmonary arrests outside of the intensive care unit (ICU) in adult inpatients. No published studies to date show significant reductions in mortality or cardiopulmonary arrests in pediatric inpatients.To determine the effect on hospital-wide mortality rates and code rates outside of the ICU setting after RRT implementation at an academic children's hospital.A cohort study design with historical controls at a 264-bed, free-standing, quaternary care academic children's hospital. Pediatric inpatients who spent at least 1 day on a medical or surgical ward between January 1, 2001, and March 31, 2007, were included. A total of 22,037 patient admissions and 102,537 patient-days were evaluated preintervention (before September 1, 2005), and 7257 patient admissions and 34,420 patient-days were evaluated postintervention (on or after September 1, 2005).The RRT included a pediatric ICU-trained fellow or attending physician, ICU nurse, ICU respiratory therapist, and nursing supervisor. This team was activated using standard criteria and was available at all times to assess, treat, and triage decompensating pediatric inpatients.Hospital-wide mortality rates and code (respiratory and cardiopulmonary arrests) rates outside of the ICU setting. All outcomes were adjusted for case mix index values.After RRT implementation, the mean monthly mortality rate decreased by 18% (1.01 to 0.83 deaths per 100 discharges; 95% confidence interval [CI], 5%-30%; P = .007), the mean monthly code rate per 1000 admissions decreased by 71.7% (2.45 to 0.69 codes per 1000 admissions), and the mean monthly code rate per 1000 patient-days decreased by 71.2% (0.52 to 0.15 codes per 1000 patient-days). The estimated code rate per 1000 admissions for the postintervention group was 0.29 times that for the preintervention group (95% likelihood ratio CI, 0.10-0.65; P = .008), and the estimated code rate per 1000 patient-days for the postintervention group was 0.28 times that for the preintervention group (95% likelihood ratio CI, 0.10-0.64; P = .007).Implementation of an RRT was associated with a statistically significant reduction in hospital-wide mortality rate and code rate outside of the pediatric ICU setting.
View details for Web of Science ID 000251055900026
View details for PubMedID 18029830
Heparin and catheter-related thrombosis in infants following cardiac surgery: Interim results from a randomized trial
80th Annual Scientific Session of the American-Heart-Association (AHA)
LIPPINCOTT WILLIAMS & WILKINS. 2007: 515–15
View details for Web of Science ID 000250394302357
Determinants of early outcome after neonatal cardiac surgery in a developing country
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2007; 134 (3): 765-771
Significant technologic advances have improved outcomes in neonatal cardiac surgery over the past 3 decades. However, outcomes might be different in developing countries with resource limitations. We sought to identify the determinants of early outcome after neonatal cardiac surgery in a tertiary referral center in South India.Hospital records of 330 consecutive neonates who underwent surgical intervention between January 1999 and April 2006 were reviewed, and perioperative variables were recorded. Main outcome measures were 30-day mortality, postoperative bloodstream infection, and hospital stay of longer than 10 days. Multivariate logistic regression analysis was performed.Overall mortality was 8.8%. Mortality significantly decreased from 21.4% before 2002 to 4.3% after 2002 (3.2% for corrective operations, P < .0001). The prevalence of postoperative bloodstream infection remained the same, whereas surgical site infection and hospital stay significantly increased after 2002. Predictors of outcomes on multivariate analysis were as follows: (1) mortality--operation before 2002 (odds ratio, 5.5), age less than 7 days (odds ratio, 3.8), preoperative antibiotic use (odds ratio, 5.6), and postoperative exchange transfusion (odds ratio, 14.9); (2) postoperative bloodstream infection (21.2%)--use of cardiopulmonary bypass (odds ratio, 2.0), reintubation (odds ratio, 7.7), and surgical site infection (odds ratio, 4.1); and (3) hospital stay of longer than 10 days (61.2%)--use of cardiopulmonary bypass (odds ratio, 2.8), delayed sternal closure (odds ratio, 3.6), reintubation (odds ratio, 12.1), surgical site infection (odds ratio, 13.8), and postoperative antibiotic use (odds ratio, 4.4).With increasing experience, neonatal cardiac surgery can be performed with excellent outcomes in developing countries with resource limitations. Infectious complications contribute significantly to morbidity and mortality, and improvements in infection-control practices should be emphasized to improve outcomes further.
View details for DOI 10.1016/j.jtcvs.2007.04.042
View details for Web of Science ID 000249013300036
View details for PubMedID 17723831
Indication for initiation of mechanical circulatory support impacts survival of infants with shunted single-ventricle circulation supported with extracorporeal membrane oxygenation
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2007; 133 (3): 660-667
The use of extracorporeal membrane oxygenation to support patients with shunted single-ventricle physiology has been controversial. Variable survivals are reported in a number of small case series. We sought to evaluate outcomes and identify predictors of survival for patients with shunted single-ventricle physiology who require extracorporeal membrane oxygenation support.We retrospectively reviewed the medical records of all patients aged less than 1 year with shunted single-ventricle physiology who were supported with extracorporeal membrane oxygenation at Children's Hospital Boston between 1996 and 2005. Survivors and nonsurvivors were compared with respect to demographics, diagnosis, operative variables, indication for extracorporeal membrane oxygenation, and extracorporeal membrane oxygenation variables.Forty-four infants with shunted single-ventricle physiology were supported with extracorporeal membrane oxygenation. Diagnoses included hypoplastic left heart syndrome (24), other single-ventricle lesions (12), and pulmonary atresia/intact ventricular septum or a variant (8). Overall survival to discharge was 48%. Indication for extracorporeal membrane oxygenation was the strongest predictor of survival to discharge, with 81% of patients cannulated for hypoxemia but only 29% of those cannulated for hypotension surviving to discharge. Specifically, patients cannulated for shunt obstruction had the highest survival (83%).Overall survival to discharge for patients with shunted single-ventricle physiology is similar to survival reported in the Extracorporeal Life Support Organization registry for all infants supported with cardiac extracorporeal membrane oxygenation. Thus, shunted single-ventricle physiology should not be considered a contraindication to extracorporeal membrane oxygenation. Patients cannulated for hypoxemia, particularly shunt thrombosis, had markedly improved survival compared with those supported primarily for hypotension/cardiovascular collapse. Survival did not differ depending on anatomic diagnosis.
View details for DOI 10.1016/j.jtcvs.2006.11.013
View details for Web of Science ID 000244441800012
View details for PubMedID 17320562
Cerebral perfusion and oxygenation after the Norwood procedure: Comparison of right ventricle-pulmonary artery conduit with modified Blalock-Taussig shunt
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2007; 133 (3): 648-655
The proposed physiologic advantage of the modified Norwood procedure using a right ventricle-pulmonary artery conduit to supply pulmonary blood flow, compared with a modified Blalock-Taussig shunt, is reduced runoff from the systemic-to-pulmonary circulation during diastole, resulting in a higher diastolic blood pressure and improved systemic perfusion. We hypothesized that the modified Norwood procedure is associated with improved cerebral perfusion and oxygenation.Transcranial Doppler sonography and near-infrared spectroscopy were performed in neonates undergoing the Norwood procedure with either a modified Blalock-Taussig shunt (n = 14) or right ventricle-pulmonary artery conduit (n = 13).Diastolic blood pressure was significantly higher in the right ventricle-pulmonary artery group at 6 hours after bypass (46 +/- 7 vs 40 +/- 4 mm Hg; P = .03), on postoperative day 1 (45 +/- 6 vs 37 +/- 5 mm Hg; P = .002), and on postoperative day 2 (46 +/- 7 vs 37 +/- 4 mm Hg; P = .001). Cerebral diastolic blood flow velocity did not differ significantly between groups at any time point or over time, but cerebral systolic blood flow velocity was higher over time in the Blalock-Taussig group (P = .01). No significant differences in regional cerebral oxygen saturation were found between groups at baseline or after bypass. Blood flow velocities and cerebral oxygen saturation did not differ significantly according to use of regional low-flow perfusion.The higher diastolic blood pressure after the modified Norwood procedure is not associated with higher cerebral blood flow velocities or regional cerebral oxygen saturation. This may imply an equal vulnerability to the cerebral injury associated with hemodynamic instability in the early postoperative period.
View details for DOI 10.1016/j.jtcvs.2006.09.034
View details for Web of Science ID 000244441800010
View details for PubMedID 17320560
Design of a large cross-sectional study to facilitate future clinical trials in children with the Fontan palliation
AMERICAN HEART JOURNAL
2006; 152 (3): 427-433
Clinical trials in children with congenital heart disease are often limited by the absence of the following: (1) a primary outcome that can be observed in a reasonable period; (2) information regarding health-related quality of life; (3) knowledge of the correlation between health status and ventricular function and exercise performance; (4) a sufficient number of children at a single institution to provide adequate statistical power; and (5) procedural and management differences between and within institutions.The NHLBI-funded Pediatric Heart Network designed a cross-sectional study of children aged 6 to 18 years, from 7 pediatric clinical centers, who had undergone a Fontan procedure as treatment for congenital heart disease. Health-related quality of life was measured by the Child Health Questionnaire and the Congenital Heart Adolescent and Teenager Questionnaire. Ventricular function was assessed by maximal exercise testing, echocardiography, cardiac magnetic resonance imaging, and B-type natriuretic peptide. The study was designed to detect a correlation of R > or = 0.30 between health status scores and measures of ventricular function and performance in a subcohort with all study measures completed.A total of 1078 children were screened by chart review; 644 (60%) were eligible. The consent rate was 85% and 546 children were enrolled. Acquisition of echocardiograms, B-type natriuretic peptide, and health status was > or = 94%; completion rates were lower for maximal exercise testing (76%) and cardiac magnetic resonance imaging (41%).This large study provides unique information regarding the relationship between health status and clinical measures in post-Fontan patients that will facilitate the design of future randomized trials.
View details for DOI 10.1016/j.ahj.2006.02.009
View details for Web of Science ID 000240564800006
View details for PubMedID 16923408
Somatic growth after ventricular septal defect in malnourished infants
JOURNAL OF PEDIATRICS
2006; 149 (2): 205-209
To assess somatic growth after ventricular septal defect (VSD) repair in severely malnourished infants.Ninety consecutive infants (age at surgery: 7.2 +/- 3.2 months) were followed after VSD closure at a referral center in southern India to evaluate somatic growth.At surgery, 44% and 30% of patients had weight and height Z score <-3, respectively. On follow-up (age 5.4 +/- 0.8 years), despite a significant improvement from baseline (Z score -1.8 +/- 1.2 vs -2.8 +/- 1.3, P <.001), weight was significantly lower compared with healthy Indian children, particularly for boys. Height Z score improved significantly only in girls (-0.8 +/- 1.3 vs -1.8+/-2.1, P = .01). Weight, height, and combined weight and height Z scores (failure to thrive) of <-2 were observed in 42%, 27%, and 18 % of patients, respectively. On multivariate analysis, weight Z score <-2 on follow-up was predicted by weight Z score at surgery and male sex, height Z score <-2 by maternal height and male sex, and failure to thrive by maternal height and caloric intake.There is suboptimal recovery of somatic growth after repair of VSD in severely malnourished infants. Preoperative malnutrition affected only weight on follow-up, whereas height recovery and failure to thrive were influenced by constitutional factors.
View details for DOI 10.1016/j.jpeds.2006.04.012
View details for Web of Science ID 000239738300015
View details for PubMedID 16887435
Homograft valved right ventricle to pulmonary artery conduit as a modification of the Norwood procedure
78th Annual Scientific Session of the American-Heart-Association
LIPPINCOTT WILLIAMS & WILKINS. 2006: I594–I599
The use of a right ventricle to pulmonary artery (RV-PA) conduit in the Norwood procedure has been proposed to increase postoperative hemodynamic stability. A valve within the conduit should further decrease RV volume load. We report our clinical experience with this modification.From February 2002 through August 2005, we performed 88 consecutive Norwood procedures using RV-PA conduits. We used composite valved conduits made from cryopreserved homograft and polytetrafluoroethylene (PTFE) in 66 cases (54 pulmonary, 12 aortic homografts), other valved conduits in 14, and unvalved PTFE in 8 cases. Hospital survival was 88.6% overall and increased to 93.1% after the initial year. Early interventions were required in 18 patients (16 for cyanosis). Prestage II cardiac catheterization was performed at a mean age of 126 days. Mean Qp/Qs was 1, with mean aortic saturation 71%, mean O2 extraction 24%, and mean right ventricular end-diastolic pressure 9 mm Hg. Patient weight, use of an aortic homograft valve in the conduit, stage I palliation within the first year of our experience, and low O2 extraction and high transpulmonary gradient prestage II were risk factors for overall death. Early interventions were more frequent in aortic valve conduits compared with all other conduits.The valved RV-PA conduit was associated with low early mortality after the Norwood procedure. The majority of these patients had normal cardiac output and well-maintained RV function. There may be a higher risk for early conduit interventions and death when aortic valve homografts are used in the RV-PA conduit.
View details for DOI 10.1161/CIRCULATIONAHA.105.001438
View details for Web of Science ID 000238688200097
View details for PubMedID 16820644
Summary proceedings from the cardiology group on postoperative cardiac dysfunction
Newborn Drug Development Initiative Workshop
AMER ACAD PEDIATRICS. 2006: S40–S46
As many as one third of the 35,000 to 40,000 infants born in the United States each year with significant congenital heart defects require surgery before the first year of life. Intraoperative support techniques, including cardiopulmonary bypass, can precipitate a complex, systemic inflammatory response that impairs the function of multiple organs and results in more hemodynamic instability and early morbidity in newborns than in older infants and children. Vasoactive agents are routinely used in the postoperative management of these patients either to treat or prevent hemodynamic instability and low cardiac output. However, the effectiveness of vasoactive agents used either individually or in combination in achieving specific therapeutic goals such as maintenance of a minimum cardiac index or arteriovenous oxygen saturation difference has not been systematically evaluated in preterm and term neonates. In addition, there are insufficient safety data for these agents in preterm and term neonates, both as individual agents and in combination. This article proposes a framework for developing prospective clinical studies to determine the efficacy of different vasoactive agents to promote adequate cardiac output and hemodynamic stability after neonatal cardiac surgery. The framework provides an overview of the issues relevant to the design of prospective clinical studies of vasoactive agents in the newborn patient population undergoing cardiac surgery. The issues identified by the cardiology group illustrate the difficulty of designing and executing clinical trials in vulnerable pediatric populations with limited numbers of patients, especially when standard practice is widely believed to be beneficial despite the lack of rigorous data to support such practice.
View details for DOI 10.1542/peds.2005-0620G
View details for Web of Science ID 000235727300006
View details for PubMedID 16777821
- Response to Haas NA and Camphausen CK: Triiodothyronine in Neonatal Heart Surgery - Looking for an Answer Journal of Thoracic and Cardiovascular Surgery 2006; 131 (2): 506
A randomized, double-blind, placebo-controlled pilot trial of triiodothyronine in neonatal heart surgery
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2005; 130 (3): 810-816
This study was undertaken to evaluate the effect of triiodothyronine replacement on the early postoperative course of neonates undergoing aortic arch reconstruction.We performed a randomized, double-blind, placebo-controlled trial of triiodothyronine supplementation in neonates undergoing either a Norwood procedure or two-ventricle repair of interrupted aortic arch and ventricular septal defect. Patients were assigned to receive a continuous infusion of triiodothyronine (0.05 micro/kg/h) or placebo for 72 hours after cardiopulmonary bypass. Primary end points were a composite clinical outcome score and cardiac index at 48 postoperative hours.We enrolled 42 patients (triiodothyronine n = 22, placebo n = 20). Baseline characteristics were similar in the treatment groups. Study drug was discontinued prematurely because of hypertension (n = 1) and ectopic atrial tachycardia (n = 1), both cases in the triiodothyronine group. Free and total triiodothyronine levels were higher in the triiodothyronine group than in the placebo group at 24, 48, and 72 postoperative hours (P < .001). The median clinical outcome scores were 2.0 (range 0-4) with triiodothyronine and 2.0 (range 0-7) with placebo (P = .046). Compared with those in the placebo group, neonates assigned to triiodothyronine had shorter median time to negative fluid balance (2.0 vs 2.5 days, P = .027). Cardiac index values were 2.11 +/- 0.64 L/min x m2 with triiodothyronine and 2.05 +/- 0.72 L/min x m2 with placebo (P = .81). Heart rate and diastolic blood pressure were not influenced by triiodothyronine supplementation, but systolic blood pressure was higher in the triiodothyronine group (P < .001). No serious adverse events were attributed to triiodothyronine administration.Triiodothyronine supplementation was safe and resulted in more rapid achievement of negative fluid balance after aortic arch reconstruction. Cardiac index at 48 hours was not significantly improved.
View details for DOI 10.1016/j.jtcvs.2005.04.025
View details for Web of Science ID 000231915400030
View details for PubMedID 16153933
Management of infants with large, unrepaired ventricular septal defects and respiratory infection requiring mechanical ventilation
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2004; 127 (5): 1466-1473
We sought to describe the hospital management and early outcome of critically ill infants presenting with large ventricular septal defects and pneumonia requiring mechanical ventilation at a referral center in a developing country. Infants with large ventricular septal defects who have pneumonia might present with respiratory failure requiring mechanical ventilation. In the developing world this presentation is relatively common, but few data exist describing patient management strategies.Hospital data of consecutive infants admitted with large ventricular septal defects and pneumonia requiring mechanical ventilation were reviewed and analyzed.We identified 18 infants (mean age, 3.6 +/- 3.0 months). On admission, all the infants were significantly malnourished, and echocardiography showed bidirectional shunting (predominantly right-to-left shunting) in 6 infants. Thirteen (72%) patients improved with intensive medical management that included mechanical ventilation for 1 to 16 days (median, 6.5 days); unequivocal left-to-right shunting was subsequently documented by means of echocardiography in all 13 patients. Twelve patients underwent surgical repair, and 11 (91.6%) were discharged after median mechanical ventilation of 100 hours (range, 42-240 hours) and intensive care unit stay of 8 days (range, 4-15 days). Five of 6 unoperated patients died, 4 of them within a few hours of admission. One child with multiple ventricular septal defects was discharged and subsequently underwent pulmonary artery banding.Corrective cardiac surgery for selected critically ill infants with large ventricular septal defects, severe malnutrition, and pneumonia requiring mechanical ventilation is feasible and should be considered a viable management strategy.
View details for DOI 10.1016/j.jtcvs.2003.11.030
View details for Web of Science ID 000221134600034
View details for PubMedID 15116009
Extracorporeal membrane oxygenation support of the Fontan and bidirectional Glenn circulations
ANNALS OF THORACIC SURGERY
2004; 77 (4): 1341-1348
Extracorporeal membrane oxygenation can provide effective mechanical circulatory support for the failing circulation in children. Patients with failing Fontan and bidirectional Glenn physiology present additional challenges both for extracorporeal membrane oxygenation cannulation and support. We report our institutional experience in patients with cavopulmonary connections who received extracorporeal membrane oxygenation.We performed a retrospective review of 20 patients with cavopulmonary connections (14 Fontan and 6 bidirectional Glenn) who were supported with extracorporeal membrane oxygenation from a single, large pediatric tertiary care center.Of the 20 patients, ten were supported and decannulated successfully (50%) (two after cardiac transplantation), but only six (30%) are alive at follow-up. Of the 14 Fontan patients, seven (50%) were withdrawn from extracorporeal membrane oxygenation or died within 48 hours of decannulation due to lack of myocardial recovery or severe neurologic injury. All four adult-sized (> 40 kg) Fontan patients were withdrawn from extracorporeal support. The seven Fontan patients who were successfully decannulated survived to discharge, and five (35.7%) are alive at follow-up (median 35 months; range, 7 to 140 months). Of the six bidirectional Glenn patients, five died before hospital discharge and the lone survivor has neurologic injury at follow-up.Patients with failing Fontan and bidirectional Glenn physiology present significant challenges to successful extracorporeal membrane oxygenation support. While the morbidity and mortality rates are high, there are select patients for whom extracorporeal support can be effective and lifesaving as a short-term resuscitative intervention.
View details for DOI 10.1016/j.athoracsur.2003.09.042
View details for Web of Science ID 000220535600044
View details for PubMedID 15063263
The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: Results of a randomized trial in infants
82nd Annual Meeting of the American-Association-for-Thoracic-Surgery
MOSBY-ELSEVIER. 2003: 1765–74
We hypothesized that cognitive impairment and hemodynamic instability after infant cardiac surgery with cardiopulmonary bypass might be exacerbated by hemodilution.In a single-center randomized trial with blinded assessment of outcomes, we compared use of 2 hemodilution protocols during hypothermic cardiopulmonary bypass with infant cardiac surgery. The primary perioperative end point was lowest cardiac index in the first 24 hours postoperatively, and primary end points at age 1 year were scores on the Psychomotor Development Index and Mental Developmental Index of the Bayley Scales.Among 147 subjects, 74 were assigned to the lower-hematocrit strategy (21.5% +/- 2.9%, mean +/- SD at onset of low-flow bypass) and 73 to the higher-hematocrit strategy (27.8% +/- 3.2%). In intent-to-treat analyses the lower-hematocrit group had lower nadirs of cardiac index (P =.02), higher serum lactate levels 60 minutes after cardiopulmonary bypass (P =.03), and a greater percentage increase in total body water on the first postoperative day (P =.006). Blood product use and adverse events were similar in the 2 groups. At age 1 year (113 children), the lower-hematocrit group had worse scores on the Psychomotor Development Index (81.9 +/- 15.7 vs 89.7 +/- 14.7, P =.008), as well as more Psychomotor Development Index scores at least 2 SDs below the population mean (16/56 [29%] vs 5/53 [9%], P =.01). The groups had similar Mental Developmental Index scores and findings on neurologic examination. Inferences using hematocrit as a continuous variable were similar to those based on intent-to-treat analyses.Hemodilution to a hematocrit level in wide use for cardiopulmonary bypass and thought to be safe is associated with adverse perioperative and developmental outcomes in infants.
View details for DOI 10.1016/j.jtcvs.2003.04.003
View details for Web of Science ID 000187560400016
View details for PubMedID 14688685
Human pulmonary valve endothelial cells express functional adhesion molecules for leukocytes
JOURNAL OF HEART VALVE DISEASE
2003; 12 (5): 617-624
Histopathological studies of rejected orthotopic heart transplants suggest that cardiac valve endothelium is spared the inflammatory cell infiltration and tissue damage that occurs in the myocardium. To test whether this apparent protection from leukocyte invasion might be an inherent feature of the valve endothelium, leukocyte adhesion molecule expression and function were analyzed in human pulmonary valve endothelial cells (HPVEC). Use of cultured HPVEC allowed delineation of the potential contribution of functional adhesion molecules from the contribution of hemodynamic forces exerted on the leaflet surface in vivoHPVEC express E-selectin, ICAM-1, and VCAM-1 in response to the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) similarly to other types of cultured human endothelial cells. In a static cell adhesion assay, E-selectin-mediated adhesion of HL-60 cells, a human promyelocytic leukemia cell line, and U937 cells, a human monocytic cell line, was determined in cells treated with TNF-alpha for 5 h. After 24 h of TNF-alpha, adhesion of U937 cells to HPVEC was mediated primarily by VCAM-1, consistent with the high expression of VCAM-1 and diminished expression of E-selectin at 24 h.These results demonstrate that HPVEC express functional leukocyte adhesion molecules in vitro and suggest that cardiac valve endothelium is competent to initiate leukocyte adhesion. Thus, other factors, such as the hemodynamic forces exerted on the valve, may contribute to the apparent protection from inflammatory cell infiltration in vivo.
View details for Web of Science ID 000185496000015
View details for PubMedID 14565715
Extracorporeal membrane oxygenation as a bridge to cardiac transplantation in a patient with cardiomyopathy and hemophilia A
INTENSIVE CARE MEDICINE
2003; 29 (6): 985-988
To report the use of extracorporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation in a patient with hemophilia A and dilated cardiomyopathy.Case report.During ECMO factor VIII concentrate was administered to maintain a factor VIII level close to 50% of normal control both to decrease the risk of bleeding and to allow standard anticoagulation with heparin. The patient developed an inhibitor to exogenous factor VIII during hospitalization, which was successfully managed with a high-dose continuous infusion of factor VIII during ECMO, the transplant operation, and the postoperative period.We report the successful use of ECMO as a bridge to cardiac transplantation in a patient with hemophilia A and low-level factor VIII inhibitors.
View details for DOI 10.1007/s00134-003-1748-5
View details for Web of Science ID 000183934800022
View details for PubMedID 12719805
Cardiovascular tissue engineering: constructing living tissue cardiac valves and blood vessels using bone marrow, umbilical cord blood, and peripheral blood cells.
journal of cardiovascular nursing
2003; 18 (1): 30-37
Although atherosclerosis and valvular heart disease are among the leading causes of morbidity and mortality in developed nations, the substitute blood vessels and heart valves currently available all have significant limitations. During the past 10 years, a new field called tissue engineering has emerged, and several research groups are focusing their efforts on constructing living tissue replacement blood vessels and heart valves. In 2001 several exciting developments occurred with the use of progenitor and stem cells. This article introduces the essential concepts of cardiovascular tissue engineering, reviews achievements in the field, discusses the basic developmental biology of heart valves and blood vessels, and summarizes the 2001 research on progenitor and stem cells.
View details for PubMedID 12537087
Cardiac catheterization of patients supported by extracorporeal membrane oxygenation
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2002; 40 (9): 1681-1686
The goal of this study was to describe the clinical outcomes of patients undergoing cardiac catheterization while supported with extracorporeal membrane oxygenation (ECMO).Extracorporeal membrane oxygenation is an important mechanical support for the failing circulation. There are diagnostic and therapeutic indications for cardiac catheterization in patients on ECMO, but no large series has been reported.We performed a retrospective review of the indications and outcomes of patients catheterized on ECMO from a single, large pediatric tertiary care center.At our institution, 192 patients with cardiac disease have undergone a total of 216 courses of ECMO; 60 catheterizations were performed on 54 patients (28%). Indications for catheterization included assessment of surgical repair (21 patients), left heart decompression (12 patients), myocarditis/cardiomyopathy assessment (10 patients), non-post-operative hemodynamic assessment (8 patients), planned catheter-based interventions (6 patients), and arrhythmia ablation (3 patients). An intervention was undertaken either during or after 50 of the catheterizations (83%); 29 occurred at catheterization, 17 in the operating room (OR), and 4 both during catheterization and in the OR. Complications during catheterization were two myocardial perforations that were treated with pericardial drains (3%). Overall outcomes included successful decannulation of 39 patients, survival to hospital discharge of 26 (48%) patients, and longer-term survival of 23 (43%) patients (median follow-up, 35 months; range, 1 to 180 months). Fifteen patients were withdrawn from ECMO support due to severe neurologic impairment or lack of myocardial recovery.Cardiac catheterization can be performed safely on patients supported with ECMO. Catheterization during ECMO enables the diagnosis of residual lesions and can facilitate important therapeutic interventions.
View details for Web of Science ID 000178946500020
View details for PubMedID 12427423
Anticipatory use of venoarterial extracorporeal membrane oxygenation for a high-risk interventional cardiac procedure.
2002; 47 (9): 1002-1006
Venoarterial extracorporeal membrane oxygenation (VA ECMO) has become a valuable technique in the critical care of children with congenital heart disease who require mechanical cardiorespiratory support. The use of VA ECMO in cardiac patients has expanded from an extension of intraoperative cardiopulmonary bypass and now includes rescue therapy during cardiopulmonary resuscitation, temporary circulatory support for reversible heart failure, and bridge support preceding heart or heart/lung transplantation. In the majority of clinical applications VA ECMO is used in reaction to impending or ongoing cardiorespiratory failure and not in anticipation of an induced change in clinical status. We describe the anticipatory use of VA ECMO to prepare a patient with complex cyanotic congenital heart disease for a high-risk interventional cardiac catheterization. A 2.5 kg neonate with severe Ebstein's anomaly of the tricuspid valve and recurrent episodes of life-threatening supraventricular tachycardia was electively cannulated for VA ECMO in the cardiac intensive care unit. She underwent successful electrophysiologic mapping and transcatheter radiofrequency ablation of an accessory conduction pathway, resulting in termination of the tachycardia. Following an uncomplicated ECMO course she was decannulated in the cardiac intensive care unit and subsequently discharged home in stable condition. The case illustrates the proactive use of ECMO during a procedure in which severe hemodynamic instability could be predicted. We discuss this concept of ECMO use in the context of accepted indications for ECMO in cardiac patients and encourage an expanded role for its use to prevent cardiorespiratory collapse in planned interventions on compromised patients who are at risk of acute deterioration.
View details for PubMedID 12188935
Outcome of ventricular septal defect repair in a developing country
JOURNAL OF PEDIATRICS
2002; 140 (6): 736-741
To examine the impact of nutrition and lung infection on outcome early after ventricular septal defect (VSD) repair in infants in a developing country.One hundred consecutive infants (age, 7.4 +/- 3.3 months) with large VSD(s) who underwent surgical repair at one institution in South India from July 1998 to June 2000 were analyzed. Primary outcome variables were postoperative death, duration of mechanical ventilation, intensive care unit (ICU) stay, and hospital stay. Preoperative variables analyzed included age, weight and length Z scores, and lung infection.Preoperative nutrition was poor (weight Z score, -2.8 +/- 1.3), and 25 patients had pneumonia. Six patients died after repair. No preoperative variable was associated with death. Mechanical ventilation, ICU stay, and hospital stay were longer for younger patients (r (s) for ventilation, -0.23, P =.02; for ICU stay, -0.33, P <.001; for hospital stay, -0.27, P =.007) and for those with preoperative pneumonia (median ventilation duration, 46 vs 24 hours, P <.001; median ICU stay 7 vs 4 days, P <.001; median hospital stay 10 vs 7 days, P =.001). Preoperative weight and length Z scores were not associated with any outcome variable.Poor nutritional status, preoperative pneumonia, and age do not increase mortality rates after VSD repair. Repair of large VSDs should not be delayed because of these preoperative characteristics.
View details for DOI 10.1067/mpd.2002.124304
View details for Web of Science ID 000176520300018
View details for PubMedID 12072879
Aortic valve endothelial cells undergo transforming growth factor-beta-mediated and non-transforming growth factor-beta-mediated transdifferentiation in vitro
AMERICAN JOURNAL OF PATHOLOGY
2001; 159 (4): 1335-1343
Cardiac valves arise from endocardial cushions, specialized regions of the developing heart that are formed by an endothelial-to-mesenchymal cell transdifferentiation. Whether and to what extent this transdifferentiation is retained in mature heart valves is unknown. Herein we show that endothelial cells from mature valves can transdifferentiate to a mesenchymal phenotype. Using induction of alpha-smooth muscle actin (alpha-SMA), an established marker for this process, two distinct pathways of transdifferentiation were identified in clonally derived endothelial cell populations isolated from ovine aortic valve leaflets. alpha-SMA expression was induced by culturing clonal endothelial cells in medium containing either transforming growth factor-beta or low levels of serum and no basic fibroblast growth factor. Cells induced to express alpha-SMA exhibited markedly increased migration in response to platelet-derived growth factor-BB, consistent with a mesenchymal phenotype. A population of the differentiated cells co-expressed CD31, an endothelial marker, along with alpha-SMA, as seen by double-label immunofluorescence. Similarly, this co-expression of endothelial markers and alpha-SMA was detected in a subpopulation of cells in frozen sections of aortic valves, suggesting the transdifferentiation may occur in vivo. Hence, the clonal populations of valvular endothelial cells described here provide a powerful in vitro model for dissecting molecular events that regulate valvular endothelium.
View details for Web of Science ID 000171411900018
View details for PubMedID 11583961
Synchronized independent lung ventilation in palliated congenital heart disease with variable sources of pulmonary blood flow.
Pediatric critical care medicine
2000; 1 (1): 79-83
OBJECTIVE: Presentation of two patient studies demonstrating the use of synchronized independent lung ventilation in the management of acute respiratory failure in patients with complex palliated congenital heart disease and variable sources of pulmonary blood flow. DESIGN: Clinical course of two patients. SETTING: Cardiac intensive care unit in a tertiary care, university-affiliated pediatric teaching hospital. PATIENTS: Patient 1 was a 22-yr-old woman with a single ventricle and right lung blood flow supplied by a classic Glenn shunt and left lung blood flow through a systemic-to-pulmonary artery shunt. Patient 2 was a 12-yr-old boy with tetralogy of Fallot and complete common atrioventricular canal defect with right lung blood flow supplied by a classic Glenn shunt and left lung blood flow supplied by the right ventricle. Both patients presented with acute, left-sided lung disease and hypoxemia. INTERVENTIONS: We used selective bronchial intubation via a double-lumen tracheal tube with a bronchial extension for synchronized independent lung ventilation to permit high-pressure ventilation of the abnormal left lung low-pressure ventilation of the normal right lung supplied by a Glenn shunt. Inhaled nitric oxide was administered to both patients and continued in one when improved oxygenation was observed. MEASUREMENTS AND MAIN RESULTS: Serial arterial blood gas measurements, mechanical indices of pulmonary function, and chest radiographs were closely followed. Synchronized independent lung ventilation contributed to improvements in systemic arterial blood oxygenation and alveolar ventilation allowing resumption of conventional ventilation in both patients. No adverse effects related to bronchial tube placement or maintenance occurred. CONCLUSION: Independent lung ventilation is an effective means of isolating the two lungs for differential ventilation, as well as the selective delivery of inhaled medications. In patients with unilateral lung disease and a Glenn shunt supplying the unaffected lung, selective lung ventilation allows aggressive treatment of the abnormal lung while optimizing flow through the Glenn shunt to maximize effective pulmonary blood flow, systemic oxygenation, and hemodynamics.
View details for PubMedID 12813292
Effects of a monoclonal antibody to P-selectin on recovery of neonatal lamb hearts after cold cardioplegic ischemia
1998; 98 (19): II391-II397
The interaction between endothelium and leukocytes plays a crucial role in ischemia-reperfusion injury. P-selectin, which is expressed on activated endothelium, mediates the first step in leukocyte adherence to the endothelium. This study examined the effects of a monoclonal antibody (mAb) against P-selectin on the recovery of cardiac function and myocardial neutrophil infiltration after ischemia.Thirteen blood-perfused, isolated neonatal lamb hearts underwent 2 hours of hypothermic cardioplegic arrest and 2 hours of reperfusion. Immediately before reperfusion, mAb to P-selectin was administered to the perfusate (15 micrograms/mL) in 6 hearts (group P-sel). In control (n = 7), the same volume of saline was added. Isovolumic left ventricular function and coronary blood flow were measured. At 2 hours after reperfusion, myocardial myeloperoxidase activity, an index of neutrophil accumulation, was assayed. At 30 minutes of reperfusion, hearts treated with mAb to P-selectin achieved significantly greater recovery of maximum developed pressure (70 +/- 4% in control versus 77 +/- 2% in group P-sel, P < 0.01), maximum positive first derivative of pressure (dP/dt) (64 +/- 7% in control versus 73 +/- 5% in group P-sel, P < 0.05), and maximum negative dP/dt (61 +/- 6% in control versus 70 +/- 6% in group P-sel, P < 0.05) compared with control. Percent baseline of coronary blood flow was also significantly increased in group P-sel (135 +/- 40% in control versus 205 +/- 43% in group P-sel, P < 0.05). Myocardial myeloperoxidase activity was significantly lower (P < 0.05) in group P-sel (4.7 +/- 3.2) versus control (16.0 +/- 10.1). (Units are change in absorbance/min/g tissue.)The functional blockade of P-selectin resulted in better recovery of cardiac function and attenuated neutrophil accumulation during early reperfusion. Strategies to block P-selectin mediated neutrophil adherence may have clinical application in improving myocardial function at early reperfusion.
View details for Web of Science ID 000076886100101
View details for PubMedID 9852932
Transendothelial chemotaxis of human alpha/beta and gamma/delta T lymphocytes to chemokines
EUROPEAN JOURNAL OF IMMUNOLOGY
1998; 28 (1): 104-113
Two subpopulations of human T lymphocytes expressing different antigen receptors, alpha/beta and gamma/delta, emigrate into inflamed tissues in distinctive patterns. We compared the transmigration of alpha/beta and gamma/delta T cells to C-C and C-X-C chemokines using an in vitro transendothelial chemotaxis assay. The C-C chemokines monocyte chemoattractant protein (MCP)-1, RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta stimulated similar, dose-dependent chemotaxis of purified gamma/delta T cells, whereas MCP-1, RANTES, and MIP-1alpha produced greater chemotaxis of purified alpha/beta T cells than MIP-1beta. In contrast, the C-X-C chemokines interleukin (IL)-8 and interferon-gamma inducible protein-10 (IP-10) did not promote chemotaxis of either alpha/beta or gamma/delta T cells. Three gamma/delta T cell clones with differing CD4 and CD8 phenotypes also migrated exclusively to C-C chemokines. Phenotypic analysis of mononuclear cells that transmigrated from an input population of unfractionated peripheral blood mononuclear cells confirmed the results with purified gamma/delta T cells. Our data demonstrate that human peripheral blood alpha/beta and gamma/delta T cells can transmigrate to MCP-1, RANTES, MIP-1alpha, and MIP-1beta, and suggest that both T lymphocyte subpopulations share the capacity to emigrate in response to C-C chemokines during inflammation.
View details for Web of Science ID 000071979400011
View details for PubMedID 9485190
Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants
77th Annual Meeting of the American-Association-for-Thoracic-Surgery
MOSBY-ELSEVIER. 1997: 991–1000
In a randomized, single-center trial, we compared perioperative outcomes in infants undergoing cardiac operations after use of the alpha-stat versus pH-stat strategy during deep hypothermic cardiopulmonary bypass.Admission criteria included reparative cardiac surgery, age less than 9 months, birth weight 2.25 kg or more, and absence of associated congenital or acquired extracardiac disorders.Among the 182 infants in the study, diagnoses included D-transposition of the great arteries (n = 92), tetralogy of Fallot (n = 50), tetralogy of Fallot with pulmonary atresia (n = 6), ventricular septal defect (n = 20), truncus arteriosus (n = 8), complete atrioventricular canal (n = 4), and total anomalous pulmonary venous return (n = 2). Ninety patients were assigned to alpha-stat and 92 to pH-stat strategy. Early death occurred in four infants (2%), all in the alpha-stat group (p = 0.058). Postoperative electroencephalographic seizures occurred in five of 57 patients (9%) assigned to alpha-stat and one of 59 patients (2%) assigned to pH-stat strategy (p = 0.11). Clinical seizures occurred in four infants in the alpha-stat group (4%) and two infants in the pH-stat group (2%) (p = 0.44). First electroencephalographic activity returned sooner among infants randomized to pH-stat strategy (p = 0.03). Within the homogeneous D-transposition subgroup, those assigned to pH-stat tended to have a higher cardiac index despite a lower requirement for inotropic agents; less frequent postoperative acidosis (p = 0.02) and hypotension (p = 0.05); and shorter duration of mechanical ventilation (p = 0.01) and intensive care unit stay (p = 0.01).Use of the pH-stat strategy in infants undergoing deep hypothermic cardiopulmonary bypass was associated with lower postoperative morbidity, shorter recovery time to first electroencephalographic activity, and, in patients with D-transposition, shorter duration of intubation and intensive care unit stay. These data challenge the notion that alpha-stat management is a superior strategy for organ protection during reparative operations in infants using deep hypothermic cardiopulmonary bypass.
View details for Web of Science ID 000071210100022
View details for PubMedID 9434694
Contrasting responses to multiple chemotactic stimuli in transendothelial migration - Heterologous desensitization in neutrophils and augmentation of migration in eosinophils
JOURNAL OF IMMUNOLOGY
1997; 158 (5): 2340-2349
At inflammatory sites in vivo, leukocytes may confront multiple, competing chemoattractive signals. We found significant differences between eosinophils and neutrophils in transendothelial chemotaxis to a chemoattractant diffusing from the lower chamber, when a chemoattractant that binds to another receptor is present at uniform concentration. The transendothelial migration of eosinophils to FMLP, C5a, RANTES, or MCP-3 was totally inhibited by the presence of the homologous chemoattractant, and only RANTES and MCP-3 showed mutual inhibition. C5a and to a lesser extent FMLP chemokinetically stimulated migration to RANTES and MCP-3, without stimulating random migration. Results with neutrophils contrasted. The presence of FMLP not only abrogated neutrophil transmigration to FMLP but also strongly decreased chemotaxis to C5a, IL-8, and Gro-alpha. Similarly, C5a inhibited neutrophil chemotaxis to IL-8 and Gro-alpha. IL-8 almost totally abrogated chemotaxis to Gro-alpha, but Gro-alpha only moderately inhibited chemotaxis to IL-8. Neither IL-8 nor Gro-alpha significantly inhibited transmigration to FMLP or C5a. Actin polymerization in eosinophils and neutrophils was desensitized by the same combinations of chemoattractants that desensitized chemotaxis. We conclude that eosinophils have at least three noninterfering receptor-signal transduction pathways for chemotaxis and actin polymerization. In contrast, the signaling pathways for FMLP, C5a, and IL-8/Gro-alpha in neutrophils are heterologously cross-desensitized, with a hierarchy of resistance to competing signals of FMLP > C5a > IL-8 > Gro-alpha, in agreement with previous results in neutrophils on the Ca2+-mobilizing response. These results may have important implications for the behavior of these cell types in inflammatory sites.
View details for Web of Science ID A1997WJ66000044
View details for PubMedID 9036983
Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta(2)-integrin CD11b/CD18
1996; 88 (1): 146-157
Platelets bound to thrombogenic surfaces have been shown to support activation-dependent firm adhesion of neutrophils in flow following selectin-mediated tethering and rolling. The specific receptor(s) responsible for mediating adhesion-strengthening interactions between neutrophils and platelets has not previously been identified. Furthermore, the ability of adherent platelets to support the migration of bound neutrophils has not been tested. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte binding in vascular shear flow and emigration at thrombogenic sites. Our results demonstrate that the beta 2-integrin Mac-1 (CD11b/CD18) is required for both firm attachment to and transmigration of neutrophils across surface-adherent platelets. In flow assays, neutrophils from patients with leukocyte adhesion deficiency-1 (LAD-I), which lack beta 2-integrin receptors, formed P-selectin-mediated rolling interactions, but were unable to develop firm adhesion to activated platelets, in contrast to healthy neutrophils, which developed firm adhesion within 5 to 30 seconds after initiation of rolling. Furthermore, the adhesion-strengthening interaction observed for healthy neutrophils could be specifically inhibited by monoclonal antibodies (mAbs) to Mac-1, but not to lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) or intercellular adhesion molecule-2 (ICAM-2; CD102). Further evidence for a beta 2-integrin-dependent neutrophil/platelet interaction is demonstrated by the complete inhibition of interleukin (IL)-8-induced neutrophil transmigration across platelets bound to fibronectin-coated polycarbonate filters by mAbs to Mac-1. Thus, Mac-1 is required for firm adhesion of neutrophils to activated, adherent platelets and may play an important role in promoting neutrophil accumulation on and migration across platelets deposited at sites of vascular injury.
View details for Web of Science ID A1996UV29700016
View details for PubMedID 8704169
Interactions of human alpha/beta and gamma/delta T lymphocyte subsets in shear flow with E-selectin and P-selectin
JOURNAL OF EXPERIMENTAL MEDICINE
1996; 183 (3): 1193-1203
We have compared the ability of human alpha/beta and gamma/delta T lymphocytes to adhere to selectin-bearing substrates, an interaction thought to be essential for homing and localization at sites of inflammation. Both T cell populations form rolling adhesions on E- and P-selectin substrates under physiologic flow conditions. Although equivalent to alpha/beta T cells in binding to E-selectin, gamma/delta T cells demonstrated greater ability to adhere to P-selectin that was purified or expressed on the surface of activated, adherent platelets. Under static conditions, 80% of gamma/delta T cells and 53% of alpha/beta T cells formed shear-resistant adhesions to P-selectin, whereas only 30% of gamma/delta and alpha/beta T cells adhered to E-selectin. The enhance ability of gamma/delta T cells to adhere to P-selectin cannot be attributed to differences in expression of the P-selectin glycoprotein ligand (PSGL-1), as all alpha/beta T cells versus approximately 75% of gamma/delta T cells expressed PSGL-1. Both cell populations expressed a similar percentage of the carbohydrate antigens sialyl LewisX and cutaneous lymphocyte-associated antigen. Depletion of lymphocyte populations or T cell clones bearing these oligosaccharides with the monoclonal antibody CSLEX-1 and HECA-452, respectively, resulted in a substantial reduction in adhesion to E-selectin and slight reduction in adhesion to P-selectin under flow conditions. Treatment of cells with an endopeptidase that selectively degrades O-sialomucins such as PSGL-1, abolished P-selectin but not E-selectin adhesion. Removal of terminal sialic acids with neuraminidase or protease treatment of cells abrogated cell adhesion to both selectin substrates. These results provide direct evidence for the presence of distinct E- and P-selectin ligands on T lymphocytes and suggest that gamma/delta T cells may be preferentially recruited to inflammatory sites during the early stages of an immune response when P-selectin is upregulated.
View details for Web of Science ID A1996UC77500051
View details for PubMedID 8642261
Effects of endothelin-1 and L-arginine after cold ischemia in lamb hearts
ANNALS OF THORACIC SURGERY
1996; 61 (1): 36-40
Prior studies from our laboratory have suggested an important role for the coronary endothelium in the injury resulting from hypothermic ischemia and reperfusion. A decreased endothelial response to intraarterial acetylcholine occurs after ischemia/reperfusion, implying a reduced release of the vasodilator nitric oxide by endothelial cells, but the role of endothelial-derived vasoconstrictor endothelin-1 in ischemia/reperfusion and interactions between endothelin-1 and nitric oxide in ischemia/reperfusion are still unclear.We examined the effects of endothelin-1 and L-arginine, the precursor for nitric oxide, on functional recovery of isolated, blood-perfused neonatal lamb hearts undergoing 2 hours of ischemia at 10 degrees C. One group (n = 8) received 10 pmol/L endothelin-1 before reperfusion, and a second group (n = 8) received a continuous infusion of 3 mmol/L L-arginine during the initial 20 minutes of reperfusion. The third group (n = 8) received both endothelin-1 and L-arginine in the same way as in the endothelin-1 and L-arginine groups. The fourth group underwent the same period of hypothermic ischemia without interventions during reperfusion.After 30 minutes of reperfusion, the endothelin-1-treated hearts showed significantly reduced recovery of left ventricular systolic function (positive maximum dP/dt and volume normalized [V10] dP/dt) and diastolic function (negative maximum dP/dt), coronary blood flow, and myocardial oxygen consumption compared with the control group (p < 0.05). These effects of endothelin-1 were offset to equal the values observed in controls having unmodified reperfusion by adding L-arginine. The L-arginine group had significantly greater recovery of left ventricular systolic function (positive maximum dP/dt, maximum developed pressure, dP/dt at V10, and developed pressure at V10) and diastolic function (negative maximum dP/dt), coronary blood flow, and myocardial oxygen consumption compared with the control group (p < 0.05).These results, combined with our previous observations that endothelin-1 levels are unchanged by hypothermic ischemia and reperfusion, suggest that there is an imbalance between the endothelial production of endothelin-1 and nitric oxide, which affects postischemic coronary blood flow and the recovery of ventricular function. Interventions that modify this imbalance of endothelially derived substances could favorably influence the outcome after a period of hypothermic ischemia and reperfusion.
View details for Web of Science ID A1996TR81800009
View details for PubMedID 8561606
Characterization of transendothelial chemotaxis of T lymphocytes
JOURNAL OF IMMUNOLOGICAL METHODS
1995; 188 (1): 97-116
We have adapted a chemotaxis assay using human umbilical vein endothelial cell (HUVEC) monolayers on microporous membranes for studying lymphocyte transendothelial chemotaxis in vitro. Supernatants of peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA) were identified as an excellent source of lymphocyte chemoattractant activity. The activity in PHA supernatant typically caused 2-6% of peripheral blood lymphocytes (PBL) to transmigrate compared to 0.1-0.3% to media control. Checkerboard analysis demonstrated that transmigration was directional and not attributable to random locomotion. Purified T lymphocytes also underwent transendothelial chemotaxis to PHA supernatant. Using monoclonal antibodies to several human adhesion receptors, we found that the interaction between LFA-1 and ICAM-1/ICAM-2 was more important for transendothelial lymphocyte chemotaxis than the interaction between VLA-4 and VCAM-1. A monoclonal antibody to the beta 1 integrin subunit inhibited chemotaxis more than antibodies to the VLA alpha 2, alpha 3, alpha 4, or alpha 5 subunits. The transendothelial assay was used to guide purification of the lymphocyte chemoattractant activity, which we reported previously to be monocyte chemoattractant protein-1 (MCP-1) (Carr et al., Proc. Natl. Acad. Sci. USA (1994) 91, 3652). The adhesion molecules required for chemotaxis to MCP-1 were similar to those with PHA supernatant. The use of HUVEC in the assay enhances the signal-to-background ratio of chemotaxis and provides a model that is physiologically relevant to lymphocyte emigration from the bloodstream into sites of inflammation.
View details for Web of Science ID A1995TN54300011
View details for PubMedID 8551044
C-C chemokines, but not the C-X-C chemokines interleukin-8 and interferon-gamma inducible protein-10, stimulate transendothelial chemotaxis of T lymphocytes
EUROPEAN JOURNAL OF IMMUNOLOGY
1995; 25 (12): 3482-3488
Eight chemokines were tested for ability to elicit transendothelial chemotaxis of unstimulated peripheral blood T lymphocytes. The C-C chemokines monocyte chemotactic protein (MCP)-2, MCP-3, RANTES, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and, as previously described, MCP-1 induced significant, dose-dependent transendothelial chemotaxis of CD3+ T lymphocytes. In contrast, the C-X-C chemokines interleukin-8 (IL-8) and interferon-gamma inducible protein-10 (IP-10) failed to induce transendothelial chemotaxis of CD3+ T lymphocytes or T lymphocyte subsets. RANTES, MIP-1 alpha, and MIP-1 beta induced significant transendothelial chemotaxis of CD4+, CD8+, and CD45R0+ T lymphocyte subsets. Phenotyping of mononuclear cells that underwent transendothelial migration to MCP-2, MCP-3, RANTES, or MIP-1 alpha showed both monocytes and activated (CD26 high), memory-type (CD45R0+) T cells. Both CD4+ and CD8+ T lymphocytes were recruited, but not natural killer cells or significant numbers of B cells. MCP-2 was the only C-C chemokine tested that attracted a significant number of naive-type (CD45RA+) T lymphocytes. In the absence of endothelium, IL-8 but not IP-10 promoted modest but significant chemotoxis of CD3+ T lymphocytes. Our data support the hypothesis that C-C, not the C-X-C chemokines IL-8 or IP-10, promote transendothelial chemotaxis of T lymphocytes.
View details for Web of Science ID A1995TL72100040
View details for PubMedID 8566041
Ten-year institutional experience with palliative surgery for hypoplastic left heart syndrome. Risk factors related to stage I mortality.
1995; 92 (9): II262-6
We reviewed 212 consecutive patients who underwent stage I palliative surgery for hypoplastic left heart syndrome (HLHS) at our institution between January 1983 and June 1993.Six surgeons participated in the care of these patients. Follow-up is 97% complete. Preoperative anatomic and physiological factors and procedural features of the stage I operation were analyzed for impact on stage I mortality, survival to stage II palliation, and actuarial survival. Hospital mortality was not significantly lower during the second half of the study period (P = .242). Operative mortality was 46.2%. Multivariate analysis revealed improved stage I operative survival in patients with mitral stenosis (MS) and aortic stenosis (AS; P = .006). Additional risk factors for stage I mortality were a lower immediately pre-stage I pH (P = .034) and weight < 3 kg (P = .015). Overall first-year actuarial survival for MS/AS was 59%, and it was 33% for all others (P = .001). Among stage I survivors, patients with MS/AS were more likely to survive to stage II palliation (P = .031). Analysis of actuarial survival of stage I survivors showed that a smaller ascending aorta (P < .001), aortic atresia (P < .001), and mitral atresia (P = .002) were all risk factors for intermediate death.Preoperative anatomic and physiological state are predictors of stage I mortality. HLHS anatomic subtype also influences intermediate outcome, most notably pre-stage II attrition. These data may be useful in choosing initial management for patients with HLHS.
View details for PubMedID 7586421
EFFECTS OF ENDOTHELIN-1 AND ENDOTHELIN-A RECEPTOR ANTAGONIST ON RECOVERY AFTER HYPOTHERMIC CARDIOPLEGIC ISCHEMIA IN NEONATAL LAMB HEARTS
67th Scientific Session of the American-Heart-Association
LIPPINCOTT WILLIAMS & WILKINS. 1995: 400–404
View details for Web of Science ID A1995TE55900067
Effects of endothelin-1 and endothelin-A receptor antagonist on recovery after hypothermic cardioplegic ischemia in neonatal lamb hearts.
1995; 92 (9): II400-4
Prior studies suggest an important role for coronary endothelium in ischemia/reperfusion (I/R) injury. Decreased endothelial release of the vasodilator nitric oxide occurs after I/R, but the role of the endothelium-derived vasoconstrictor endothelin-1 (ET-1) in I/R is unknown.We measured plasma ET-1 concentrations by radioimmunoassay in isolated blood-perfused neonatal lamb hearts before and after 2 hours of 10 degrees C cardioplegic ischemia and examined the effects of ET-1 and the endothelin-A (ET-A) receptor antagonist BE-18257B on the postischemic recovery of isolated hearts. ET-1 levels in coronary sinus blood before ischemia and at 0 and 30 minutes of reperfusion in 8 control hearts were constant (2.2 +/- 1.2 fmol/L, 2.2 +/- 1.3 fmol/L, and 2.5 +/- 1.0 fmol/L, respectively). In group 2 (n = 6), 10 mumol/L of BE-18257B was given just before reperfusion. In group 3 (n = 8), 10 pmol/L ET-1 was given just before the start of reperfusion. At 30 minutes of reperfusion, the ET-A antagonist hearts had significantly greater recovery of LV systolic (positive dP/dt and dP/dt at V10) and diastolic function (negative dP/dt), coronary blood flow (CBF), and MVo2 compared with controls (P < .05). The ET-1 hearts showed significantly reduced recovery of LV systolic (positive maximum and volume-normalized dP/dt) and diastolic (negative maximum dP/dt) function, CBF, and myocardial oxygen consumption compared with controls (P < .05).These results, combined with prior studies, suggest that I/R causes reduced production of endogenous vasodilators (eg, nitric oxide), leaving unopposed the vasoconstriction that is caused by the continued presence of ET-1. This imbalance may contribute to I/R injury. ET-A receptor antagonists may be useful therapeutic agents in reducing the injury that results from I/R.
View details for PubMedID 7586445
MONOCYTE CHEMOATTRACTANT PROTEIN-1 ACTS AS A T-LYMPHOCYTE CHEMOATTRACTANT
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
1994; 91 (9): 3652-3656
We have utilized a transendothelial lymphocyte chemotaxis assay to identify and purify a lymphocyte chemoattractant in supernatants of mitogen-stimulated peripheral blood mononuclear cells. Amino acid sequence analysis revealed identity with monocyte chemoattractant protein 1 (MCP-1), a chemoattractant previously thought to be specific for monocytes. Recombinant MCP-1 is chemoattractive for purified T lymphocytes and for CD3+ lymphocytes in peripheral blood lymphocyte preparations. The T-cell response to MCP-1 is dose-dependent and chemotactic, rather than chemokinetic. Phenotyping of chemoattracted T lymphocytes shows they are an activated memory subset. The response to MCP-1 by T lymphocytes can be duplicated in the absence of an endothelial monolayer and the majority of T-lymphocyte chemotactic activity in mitogen-stimulated peripheral blood mononuclear cell supernatants can be neutralized by antibody to MCP-1. Thus, MCP-1 is the major lymphocyte chemoattractant secreted by mitogen-stimulated peripheral blood mononuclear cells and is capable of acting as a potent T-lymphocyte, as well as monocyte, chemoattractant. This may help explain why monocytes and T lymphocytes of the memory subset are always found together at sites of antigen-induced inflammation.
View details for Web of Science ID A1994NJ03400038
View details for PubMedID 8170963