Ronald Pearl

All Publications

• Development of and recovery from acute kidney injury after cardiac surgery: Randomized phase 2 trial of the hepatocyte growth factor mimetic ANG-3777. The Journal of thoracic and cardiovascular surgery Ayad, S. S., Beaver, T., Corteville, D., Swaminathan, M., Pearl, R. G., Aslam, S., Csomor, P. A., Alperovich, G., Neylan, J. 2024

  Abstract

  To investigate the safety and efficacy of ANG-3777, a hepatocyte growth factor mimetic, in mitigating the risk of acute kidney injury (AKI) in patients undergoing cardiac surgery with cardiopulmonary bypass.In this double-blind placebo-controlled study (GUARD), patients were randomized to receive intravenous ANG-3777 2 mg/kg or placebo once daily for 4 days. The primary endpoint was AKI severity, measured by mean area under the concentration-time curve on percent increase in serum creatinine from days 2 to 6. Secondary endpoints included the proportions of patients who developed major adverse kidney events by day 30 or 90 and the percentage of patients diagnosed with AKI through day 5.In total, 259 patients received study treatment (ANG-3777, n = 129; placebo, n = 130). Through day 6, there was no significant difference in least-squares mean change in serum creatinine between ANG-3777 and placebo (1.1%; 95% CI, -6.2, 8.4; P = .77), or in proportions of patients who developed major adverse kidney events by day 30 (18.6% vs 16.2%; P = .60) or day 90 (14.7% vs 21.5%; P = .16). Similar proportions of patients were diagnosed with AKI through day 5 (ANG-3777, 47.3%; placebo, 48.5%); however, exploratory analysis revealed more patients diagnosed with AKI postoperatively showed signs of recovery following treatment with ANG-3777 than placebo. Overall, ANG-3777 was well tolerated, with similar incidences of treatment-emergent adverse events between treatment arms.Findings from this study do not support the efficacy of ANG-3777 in preventing the development of AKI following cardiopulmonary bypass.

  View details for DOI 10.1016/j.jtcvs.2024.11.024

  View details for PubMedID 39603491

• Tracheal intubation in critically ill adults with a physiologically difficult airway. An international Delphi study INTENSIVE CARE MEDICINE Karamchandani, K., Nasa, P., Jarzebowski, M., Brewster, D. J., De Jong, A., Bauer, P. R., Berkow, L., Brown, C. A., Cabrini, L., Casey, J., Cook, T., Divatia, J., Duggan, L. V., Ellard, L., Ergan, B., Fagerlund, M., Gatward, J., Greif, R., Higgs, A., Jaber, S., Janz, D., Joffe, A. M., Jung, B., Kovacs, G., Kwizera, A., Laffey, J. G., Lascarrou, J., Law, J., Marshall, S., McGrath, B. A., Mosier, J. M., Perin, D., Roca, O., Rolle, A., Russotto, V., Sakles, J. C., Shrestha, G. S., Smischney, N. J., Sorbello, M., Tung, A., Jabaley, C. S., Myatra, S., SOCCA Physiologically Difficult A 2024

  Abstract

  Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA).An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician-researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements.The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care.Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties.

  View details for DOI 10.1007/s00134-024-07578-2

  View details for Web of Science ID 001294905500005

  View details for PubMedID 39162823

  View details for PubMedCentralID 7988368

• Correction to: Bayesian methods: a potential path forward for sepsis trials. Critical care (London, England) Tomlinson, G., Al-Khafaji, A., Conrad, S. A., Factora, F. N., Foster, D. M., Galphin, C., Gunnerson, K. J., Khan, S., Kohli-Seth, R., McCarthy, P., Meena, N. K., Pearl, R. G., Rachoin, J. S., Rains, R., Seneff, M., Tidswell, M., Walker, P. M., Kellum, J. A. 2024; 28 (1): 11

  View details for DOI 10.1186/s13054-023-04791-1

  View details for PubMedID 38172963

  View details for PubMedCentralID PMC10765909

• Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial. Trials Snyder, E. L., Sekela, M. E., Welsby, I. J., Toyoda, Y., Alsammak, M., Sodha, N. R., Beaver, T. M., Pelletier, J. P., Gorham, J. D., McNeil, J. S., Sniecinski, R. M., Pearl, R. G., Nuttall, G. A., Sarode, R., Reece, T. B., Kaplan, A., Davenport, R. D., Ipe, T. S., Benharash, P., Lopez-Plaza, I., Gammon, R. R., Sadler, P., Pitman, J. P., Liu, K., Bentow, S., Corash, L., Mufti, N., Varrone, J., Benjamin, R. J. 2023; 24 (1): 799

  Abstract

  Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies.ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%.RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

  View details for DOI 10.1186/s13063-023-07831-x

  View details for PubMedID 38082326

  View details for PubMedCentralID 4142007

• Bayesian methods: a potential path forward for sepsis trials. Critical care (London, England) Tomlinson, G., Al-Khafaji, A., Conrad, S. A., Factora, F. N., Foster, D. M., Galphin, C., Gunnerson, K. J., Khan, S., Kohli-Seth, R., McCarthy, P., Meena, N. K., Pearl, R. G., Rachoin, J. S., Rains, R., Seneff, M., Tidswell, M., Walker, P. M., Kellum, J. A. 2023; 27 (1): 432

  Abstract

  Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods.We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60-0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment.In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored.Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.

  View details for DOI 10.1186/s13054-023-04717-x

  View details for PubMedID 37940985

  View details for PubMedCentralID 4968574

• Racial and Ethnic Disparities in Veno-Venous Extracorporeal Membrane Oxygenation Mortality for Patients With Severe Coronavirus Disease-2019. ASAIO journal (American Society for Artificial Internal Organs : 1992) Kopanczyk, R., Lisco, S. J., Pearl, R., Demiralp, G., Naik, B. I., Mazzeffi, M. A. 2023

  Abstract

  Racial/ethnic disparities in mortality were observed during the coronavirus disease-2019 pandemic, but investigations examining the association between race/ethnicity and mortality during extracorporeal membrane oxygenation (ECMO) are limited. We performed a retrospective observational cohort study using the 2020 national inpatient sample. Multivariable logistic regression was used to estimate the odds of mortality in patients of difference race/ethnicity while controlling for confounders. There was a significant association between race/ethnicity and in-hospital mortality (p < 0.001). Hispanic patients had significantly higher in-hospital mortality compared with White patients (odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.16-1.67, p < 0.001). Black patients and patients of other races did not have significantly higher in-hospital mortality compared with White patients (OR = 0.82, 95% CI = 0.66-1.02, p = 0.07 and OR = 1.20, 95% CI = 0.92-1.57, p = 0.18). Other variables that had a significant association with mortality included age, insurance type, Charlson comorbidity index, all patient-refined severity of illness, and receipt of care in a low-volume ECMO center (all p < 0.001). Further studies are needed to understand causes of disparities in ECMO mortality.

  View details for DOI 10.1097/MAT.0000000000002072

  View details for PubMedID 37815999

• Development of the Modern Cardiothoracic Intensive Care Unit and Current Management. Critical care clinics Pearl, R. G., Cole, S. P. 2023; 39 (3): 559-576

  Abstract

  The modern cardiothoracic intensive care unit (CTICU) developed as a result of advances in critical care, cardiology, and cardiac surgery. Patients undergoing cardiac surgery today are sicker, frailer, and have more complex cardiac and noncardiac morbidities. CTICU providers need to understand postoperative implications of different surgical procedures, complications that can occur in CTICU patients, resuscitation protocols for cardiac arrest, and diagnostic and therapeutic interventions such as transesophageal echocardiography and mechanical circulatory support. Optimum CTICU care requires a multidisciplinary team with collaboration between cardiac surgeons and critical care physicians with training and experience in the care of CTICU patients.

  View details for DOI 10.1016/j.ccc.2023.03.008

  View details for PubMedID 37230556

• Pain Management: Optimizing Patient Care Through Comprehensive, Interdisciplinary Models and Continuous Innovations. Anesthesiology clinics Mackey, S. C., Pearl, R. G. 2023; 41 (2): xv-xvii

  View details for DOI 10.1016/j.anclin.2023.03.011

  View details for PubMedID 37245956

• COVID-19: Common Critical and Practical Questions. Anesthesia and analgesia Lu, A. C., Sastry, S. G., Wong, B. J., Deng, A., Wald, S. H., Pearl, R. G., Tsui, B. C. 2020

  View details for DOI 10.1213/ANE.0000000000004938

  View details for PubMedID 32366770

• N95 Respirator Alternatives And Conservation Strategies. Anesthesia and analgesia Wong, B. J., Lu, A. C., Tarlow, B. D., Tompkins, L. S., Chawla, A. n., Pearl, R. G., Wald, S. H. 2020

  View details for DOI 10.1213/ANE.0000000000005134

  View details for PubMedID 32701549

• Resuscitation on collapsed healthcare worker while taking care of suspected or confirmed COVID patient: Questions and Answers. Anesthesia and analgesia Lu, A. C., Wong, B. J., Sastry, S. G., Wald, S. H., Pearl, R. G., Tsui, B. C. 2020

  View details for DOI 10.1213/ANE.0000000000005136

  View details for PubMedID 32701548

• An Anesthesia Attempt to Be Green: How Do You Waste Your Carbon Dioxide Absorbers? A&A practice Burbridge, M. A., Chua, P. n., Jaffe, R. A., Pearl, R. G., Brock-Utne, J. G. 2019

  Abstract

  Operating room waste is categorized as noncontaminated solid waste (SW) and regulated medical waste (RMW). RMW is treated by autoclaving at an increased economic and environmental cost. We evaluated these costs with a focus on the disposable carbon dioxide (CO2) absorbers. At our institution, exhausted CO2 absorbers were discarded as RMW. We collaborated with product representatives, anesthesia and perioperative staff, and waste management personnel to identify opportunities and barriers for recycling and waste reduction. Ultimately, we agreed to discard CO2 absorbers as SW instead of RMW, a strategy that is practical, less expensive, and more environmentally appropriate.

  View details for DOI 10.1213/XAA.0000000000001113

  View details for PubMedID 31609724

• AN ANESTHETIC ATTEMPT TO BE GREEN: HOW DO YOU WASTE YOUR CO2 ABSORBERS? Chua, P., Brock-Utne, J., Burbridge, M. A., Pearl, R., Alejandro-Harper, D., Kimball, E., Gilsenan, C. LIPPINCOTT WILLIAMS & WILKINS. 2018: 226–27

  View details for Web of Science ID 000460106500120

• Nocturnal Low-Dose Propofol Infusion for the Management of ICU Delirium: A Case Series in Nonintubated Cardiac Surgery Patients. Journal of cardiothoracic and vascular anesthesia Wong, J. K., Nikravan, S., Maxwell, B. G., Marques, M. A., Pearl, R. G. 2016; 30 (5): 1340-1343

  View details for DOI 10.1053/j.jvca.2016.02.002

  View details for PubMedID 27423473

• Obstructive Sleep Apnea Is an Independent Predictor of Postoperative Atrial Fibrillation in Cardiac Surgery JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Wong, J. K., Maxwell, B. G., Kushida, C. A., Sainani, K. L., Lobato, R. L., Woo, J., Pearl, R. G. 2015; 29 (5): 1140-1147

  Abstract

  To test the hypothesis that obstructive sleep apnea (OSA) is a risk factor for development of postoperative atrial fibrillation (POAF) after cardiac surgery.Retrospective analysis.Single-center university hospital.Five hundred forty-five patients in sinus rhythm preoperatively undergoing coronary artery bypass grafting (CABG), aortic valve replacement, mitral valve replacement/repair, or combined valve/CABG surgery from January 2008 to April 2011.Retrospective review of medical records.Postoperative atrial fibrillation was defined as atrial fibrillation requiring therapeutic intervention. Of 545 cardiac surgical patients, 226 (41%) patients developed POAF. The risk was higher in 72 OSA patients than 473 patients without OSA (67% v 38%, adjusted hazard ratio 1.83 [95% CI: 1.30-2.58], p<0.001). Of the 32 OSA patients who used home positive airway pressure (PAP) therapy, 18 (56%) developed POAF compared with 29 of 38 (76%) patients who did not use PAP at home (unadjusted hazard ratio 0.63 [95% CI: 0.35-1.15], p = 0.13).OSA is significantly associated with POAF in cardiac surgery patients. Further investigation is needed to determine whether or not use of positive airway pressure in OSA patients reduces the risk of POAF.

  View details for DOI 10.1053/j.jvca.2015.03.024

  View details for PubMedID 26154572

• Future of Anesthesiology Is Perioperative Medicine A Call for Action ANESTHESIOLOGY Kain, Z. N., Fitch, J. C., Kirsch, J. R., Mets, B., Pearl, R. G. 2015; 122 (6): 1192-1195

  View details for DOI 10.1097/ALN.0000000000000680

  View details for PubMedID 25886775

• Predictors of contemporary coronary artery bypass grafting outcomes JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Weisel, R. D., Nussmeier, N., Newman, M. F., Pearl, R. G., Wechsler, A. S., Ambrosio, G., Pitt, B., Clare, R. M., Pieper, K. S., Mongero, L., Reece, T. L., Yau, T. M., Fremes, S., Menasche, P., Lira, A., Harrington, R. A., Ferguson, T. B. 2014; 148 (6): 2720-U1368

  Abstract

  The study objective was to identify the predictors of outcomes in a contemporary cohort of patients from the Reduction in cardiovascular Events by acaDesine in patients undergoing CABG (RED-CABG) trial. Despite the increasing risk profile of patients who undergo coronary artery bypass grafting, morbidity and mortality have remained low, and identification of the current predictors of adverse outcomes may permit new treatments to further improve outcomes.The RED-CABG trial was a multicenter, randomized, double-blind, placebo-controlled study that determined that acadesine did not reduce adverse events in moderately high-risk patients undergoing nonemergency coronary artery bypass grafting. The primary efficacy end point was a composite of all-cause death, nonfatal stroke, or the need for mechanical support for severe left ventricular dysfunction through postoperative day 28. Logistic regression modeling with stepwise variable selection identified which prespecified baseline characteristics were associated with the primary outcome. A second logistic model included intraoperative variables as potential covariates.The 4 independent preoperative risk factors predictive of the composite end point were (1) a history of heart failure (odds ratio, 2.9); (2) increasing age (odds ratio, 1.033 per decade); (3) a history of peripheral vascular disease (odds ratio, 1.6); and (4) receiving aspirin before coronary artery bypass grafting (odds ratio, 0.5), which was protective. The duration of the cardiopulmonary bypass (odds ratio, 1.8) was the only intraoperative variable that contributed to adverse outcomes.Patients who had heart failure and preserved systolic function had a similar high risk of adverse outcomes as those with low ejection fractions, and new approaches may mitigate this risk. Recognition of patients with excessive atherosclerotic burden may permit perioperative interventions to improve their outcomes. The contemporary risks of coronary artery bypass grafting have changed, and their identification may permit new methods to improve outcomes.

  View details for DOI 10.1016/j.jtcvs.2014.08.018

  View details for Web of Science ID 000345686100064

  View details for PubMedID 25218533

• Review: Noninvasive vs invasive weaning from mechanical ventilation reduces mortality in respiratory failure ANNALS OF INTERNAL MEDICINE Pearl, R. G. 2014; 160 (12): JC8

  View details for DOI 10.7326/0003-4819-160-12-201406170-02008

  View details for Web of Science ID 000337374900008

  View details for PubMedID 24935514

• Endothelial fate mapping in mice with pulmonary hypertension. Circulation Qiao, L., Nishimura, T., Shi, L., Sessions, D., Thrasher, A., Trudell, J. R., Berry, G. J., Pearl, R. G., Kao, P. N. 2014; 129 (6): 692-703

  Abstract

  Pulmonary endothelial injury triggers a reparative program, which in susceptible individuals is characterized by neointima formation, vascular narrowing, and the development of pulmonary arterial hypertension. The neointimal cells in human pathological plexiform lesions frequently coexpress smooth muscle α-actin and the endothelial von Willebrand antigen, creating a question about their cellular lineage of origin.Experimental pulmonary hypertension with neointima formation develops in C57Bl/6 mice subjected to left pneumonectomy followed 1 week later by jugular vein injection of monocrotaline pyrrole (20 μg/μL and 1 μL/g; group P/MCTP). Compared with the group vehicle, by day 35, group P/MCTP developed higher right ventricular systolic pressure (54±5 versus 25±2 mm Hg; P<0.01) and right ventricular hypertrophy (0.58±0.16 versus 0.26±0.05; P<0.01). Transgenic vascular endothelial-cadherin Cre recombinase or Tie-2 Cre mice were intercrossed with mTomato/mGreen fluorescent protein double-fluorescent Cre reporter mice to achieve endothelial genetic lineage marking with membrane-targeted green fluorescent protein. In control mice, few endothelial lineage-marked cells lining the lumen of small pulmonary arteries demonstrate expression of smooth muscle α-actin. Concurrent with the development of pulmonary hypertension, endothelial lineage-marked cells are prominent in the neointima and exhibit expression of smooth muscle α-actin and smooth muscle myosin heavy chain. Human pulmonary arterial hypertension neointimal lesions contain cells that coexpress endothelial CD31 or von Willebrand antigen and smooth muscle α-actin.Neointimal cells in pulmonary hypertension include contributions from the endothelial genetic lineage with induced expression of smooth muscle α-actin and smooth muscle myosin heavy chain.

  View details for DOI 10.1161/CIRCULATIONAHA.113.003734

  View details for PubMedID 24201301

• Erythropoietin and organ protection: lessons from negative clinical trials CRITICAL CARE Pearl, R. G. 2014; 18 (5): 526

  Abstract

  Based on its pleiotropic effects, erythropoietin can decrease inflammation, oxidative stress, and apoptosis. Erythropoietin provides organ protection for the heart, brain, and kidney in diverse preclinical animal studies, especially models that include ischemia-reperfusion injury and/or inflammation. However, large clinical studies in coronary reperfusion, heart failure, stroke, acute kidney injury, and chronic renal disease have failed to demonstrate improved outcomes. A study in a previous issue of Critical Care examining the ability of erythropoietin to prevent or ameliorate acute kidney injury in patients undergoing complex valvular heart surgery is similarly negative. The failure of erythropoietin in clinical studies may be due to an inadequate dose, since the receptors responsible for organ protection may require higher concentrations than those responsible for erythropoiesis. However, as has occurred in studies in sepsis and acute respiratory distress syndrome, the negative studies probably reflect an inadequate understanding of the complexity of the underlying processes with multiple redundant and interacting pathways that may differ among the large number of different cell types involved. As tools to understand this complexity and integrate it on an organismal basis continue to evolve, we will develop the ability to use erythropoietin and related nonhematopoietic agents for organ protection.

  View details for DOI 10.1186/s13054-014-0526-9

  View details for Web of Science ID 000351850600044

  View details for PubMedID 25672222

  View details for PubMedCentralID PMC4331307

• Tezosentan and Right Ventricular Failure in Patients With Pulmonary Hypertension Undergoing Cardiac Surgery: The TACTICS Trial JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Denault, A. Y., Pearl, R. G., Michler, R. E., Rao, V., Tsui, S. L., Seitelberger, R., Cromie, M., Lindberg, E., D'Armini, A. M. 2013; 27 (6): 1212–17

  Abstract

  To evaluate the efficacy of tezosentan in reducing the incidence of right ventricular (RV) failure and associated mortality in patients with pre-existing pulmonary hypertension. The primary endpoint was the proportion of patients with RV failure during weaning from cardiopulmonary bypass (CPB), assessed 30 minutes after the end of CPB.Multicenter, double-blind, randomized, placebo-controlled trial.Thirty-one cardiac surgical centers in 14 countries.Two hundred seventy-four patients with pulmonary hypertension aged ≥ 18 years scheduled to undergo cardiac surgery.Intravenous tezosentan (5 mg/h) during surgery and up to 24 hours afterwards (1 mg/h), or matched placebo.One-hundred thirty-three patients received tezosentan and 141 placebo. RV failure occurred in 30 patients (10.9%), 37% of whom died. There was no difference in the incidence of RV failure between the two treatment groups (relative risk reduction: 0.07 [95% CI-0.83, 0.53; P = 0.8278]).A reduction in RV failure with tezosentan was not observed in this study.(Current Controlled Trials, identifier NCT00458276).

  View details for DOI 10.1053/j.jvca.2013.01.023

  View details for Web of Science ID 000328181700022

  View details for PubMedID 23523254

• Focused transthoracic echocardiography during critical care medicine training: curriculum implementation and evaluation of proficiency*. Critical care medicine Beraud, A., Rizk, N. W., Pearl, R. G., Liang, D. H., Patterson, A. J. 2013; 41 (8): e179-81

  Abstract

  OBJECTIVES:: We designed and implemented a focused transthoracic echocardiography curriculum for critical care medicine fellows participating in 1- and 2-year training programs. We quantitatively evaluated their proficiency in focused transthoracic echocardiography. DESIGN:: Prospective study evaluating curriculum implementation and objective assessment of focused transthoracic echocardiography proficiency. SETTING:: Medical and surgical ICUs at an academic teaching hospital. Simulation laboratory. SUBJECTS:: Eighteen critical care medicine fellows. INTERVENTIONS:: Training in focused transthoracic echocardiography followed by proficiency testing. MEASUREMENTS AND MAIN RESULTS:: We assessed the ability of critical care medicine fellows to obtain and interpret focused transthoracic echocardiography images from critically ill patients and a from transthoracic echocardiography simulator. Using a cognitive examination test, we also evaluated each fellow's knowledge with regard to focused transthoracic echocardiography and each fellow's ability to interpret prerecorded focused transthoracic echocardiography images. After training, critical care medicine fellows were able to rapidly obtain five essential focused transthoracic echocardiography views: parasternal long axis, parasternal short axis, apical four chamber, subcostal four chamber, and subcostal inferior vena cava. Fellows were also able to expeditiously identify four important abnormalities: asystole, left ventricular dysfunction, right ventricular dilation and dysfunction, and a large pericardial effusion. CONCLUSIONS:: A focused transthoracic echocardiography curriculum that includes quantitative measures of proficiency can be integrated into critical care medicine fellowship training programs.

  View details for DOI 10.1097/CCM.0b013e31828e9240

  View details for PubMedID 23760156

• Focused transthoracic echocardiography during critical care medicine training: curriculum implementation and evaluation of proficiency*. Critical care medicine Beraud, A., Rizk, N. W., Pearl, R. G., Liang, D. H., Patterson, A. J. 2013; 41 (8): e179-81

  View details for DOI 10.1097/CCM.0b013e31828e9240

  View details for PubMedID 23760156

• Preparing Interns for Anesthesiology Residency Training: Development and Assessment of the Successful Transition to Anesthesia Residency Training (START) E-Learning Curriculum. Journal of graduate medical education Chu, L. F., Ngai, L. K., Young, C. A., Pearl, R. G., Macario, A., Harrison, T. K. 2013; 5 (1): 125-129

  Abstract

  The transition from internship to residency training may be a stressful time for interns, particularly if it involves a change among programs or institutions after completing a preliminary year.We explored whether an e-learning curriculum would increase interns' preparedness for the transition to the first year of clinical anesthesiology training and reduce stress by improving confidence and perceived competence in performing professional responsibilities.We tested a 10-month e-learning program, Successful Transition to Anesthesia Residency Training (START), as a longitudinal intervention to increase interns' self-perceived preparedness to begin anesthesiology residency training in a prospective, observational study and assessed acceptance and sustainability. After a needs assessment, we administered the START modules to 22 interns, once a month, using an integrated learning management and lecture-capture system. We surveyed interns' self-assessed preparedness to begin anesthesiology residency before and after completing the START modules. Interns from the prior year's class, who did not participate in the online curriculum, served as controls.After participation in the START intervention, self-assessed preparedness to begin residency improved by 72% (P  =  .02). Interns also felt more connected to, and had improved positive feelings toward, their new residency program and institution.Participation in our novel 10-month e-learning curriculum and virtual mentorship program improved interns' impression of their residency program and significantly increased interns' subjective assessment of their preparedness to begin anesthesiology residency. This e-learning concept could be more broadly applied and useful to other residency programs.

  View details for DOI 10.4300/JGME-D-12-00121.1

  View details for PubMedID 24404239

  View details for PubMedCentralID PMC3613296

• Review: Etomidate increased mortality and adrenal insufficiency in adults with sepsis ANNALS OF INTERNAL MEDICINE Pearl, R. G. 2013; 158 (4)

  View details for DOI 10.7326/0003-4819-158-4-201302190-02010

  View details for Web of Science ID 000315580300009

• Understanding the Divergent Effects of Norepinephrine on Cardiac Output: Go With the Flow CRITICAL CARE MEDICINE Pearl, R. G. 2013; 41 (1): 352-354

  View details for DOI 10.1097/CCM.0b013e318270e67e

  View details for Web of Science ID 000313150300048

  View details for PubMedID 23269148

• Airway Management and Perioperative Decision Making in the Patient With Severe Pulmonary Hypertension Who Requires Emergency Noncardiac Surgery JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Maxwell, B. G., Pearl, R. G., Kudelko, K. T., Zamanian, R. T., Hill, C. C. 2012; 26 (5): 940-944

  View details for DOI 10.1053/j.jvca.2012.06.018

  View details for PubMedID 22943790

• Effect of Adenosine-Regulating Agent Acadesine on Morbidity and Mortality Associated With Coronary Artery Bypass Grafting The RED-CABG Randomized Controlled Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Newman, M. F., Ferguson, T. B., White, J. A., Ambrosio, G., Koglin, J., Nussmeier, N. A., Pearl, R. G., Pitt, B., Wechsler, A. S., Weisel, R. D., Reece, T. L., Lira, A., Harrington, R. A. 2012; 308 (2): 157-164

  Abstract

  Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery bypass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery.To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days.The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010.Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction.Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28.Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured.In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD.clinicaltrials.gov Identifier: NCT00872001.

  View details for Web of Science ID 000306219500029

  View details for PubMedID 22782417

• Self-Reported Information Needs of Anesthesia Residency Applicants and Analysis of Applicant-Related Web Sites Resources at 131 United States Training Programs ANESTHESIA AND ANALGESIA Chu, L. F., Young, C. A., Zamora, A. K., Lowe, D., Hoang, D. B., Pearl, R. G., Macario, A. 2011; 112 (2): 430-439

  Abstract

  Despite the use of web-based information resources by both anesthesia departments and applicants, little research has been done to assess these resources and determine whether they are meeting applicant needs. Evidence is needed to guide anesthesia informatics research in developing high-quality anesthesia residency program Web sites (ARPWs).We used an anonymous web-based program (SurveyMonkey, Portland, OR) to distribute a survey investigating the information needs and perceived usefulness of ARPWs to all 572 Stanford anesthesia residency program applicants. A quantitative scoring system was then created to assess the quality of ARPWs in meeting the information needs of these applicants. Two researchers independently analyzed all 131 ARPWs in the United States to determine whether the ARPWs met the needs of applicants based on the scoring system. Finally, a qualitative assessment of the overall user experience of ARPWs was developed to account for the subjective elements of the Web site's presentation.Ninety-eight percent of respondents reported having used ARPWs during the application process. Fifty-six percent reported first visiting the Stanford ARPW when deciding whether to apply to Stanford's anesthesia residency program. Multimedia and Web 2.0 technologies were "very" or "most" useful in "learning intangible aspects of a program, like how happy people are" (42% multimedia and Web 2.0 versus 14% text and photos). ARPWs, on average, contained only 46% of the content items identified as important by applicants. The average (SD) quality scores among all ARPWs was 2.06 (0.59) of 4.0 maximum points. The mean overall qualitative score for all 131 ARPWs was 4.97 (1.92) of 10 points. Only 2% of applicants indicated that the majority (75%-100%) of Web sites they visited provided a complete experience.Anesthesia residency applicants rely heavily on ARPWs to research programs, prepare for interviews, and formulate a rank list. Anesthesia departments can improve their ARPWs by including information such as total hours worked and work hours by rotation (missing in 96% and 97% of ARPWs) and providing a valid web address on the Fellowship and Residency Electronic Interactive Database Access System (FREIDA) (missing in 28% of ARPWs).

  View details for DOI 10.1213/ANE.0b013e3182027a94

  View details for PubMedID 21081766

• A Prospective Randomized Pilot Study of Near-Infrared Spectroscopy-Directed Restricted Fluid Therapy versus Standard Fluid Therapy in Patients Undergoing Elective Colorectal Surgery AMERICAN SURGEON Cohn, S. M., Pearl, R. G., Acosta, S. M., Nowlin, M. U., Hernandez, A., Guta, C., Michalek, J. E. 2010; 76 (12): 1384-1392

  Abstract

  There are substantial data supporting the concept that algorithms that effectively limit fluid volumes to patients undergoing elective surgery, particularly intraoperatively, significantly reduce perioperative morbidity. We hypothesized that intraoperative fluid limitation could be safely accomplished when guided by near-infrared spectroscopy (NIRS) monitoring, and that this fluid restriction regimen would result in a reduction in postoperative morbidity when compared with standard monitoring and fluid therapy. The intent of this pilot study was to demonstrate the feasibility and ease of conduct of this study protocol before expanding to the multicenter pivotal trial. We performed a prospective, (2:1) randomized, pilot study at two centers. A total enrollment of 24 fully evaluable patients undergoing elective open colorectal surgery (16 restricted, 8 standard) was planned. After providing informed consent, patients were randomized to standard fluid resuscitation (500 LR induction bolus, then LR 7 mL/kg/h x 1 h, then 5 mL/kg/h) or restricted fluid resuscitation (no induction bolus, then LR 2 mL/kg/h). Subsequent fluid bolus infusions were guided by physiologic parameters (systolic blood pressure < 90 mm Hg, heart rate > 100 bpm, or oliguria) in the standard group, and by tissue oxygen saturation from NIRS (tissue oxygen saturation (StO2) < 75%, or 20% below baseline; or the same physiologic parameters) in the restricted group. Primary endpoints were major postoperative complications. A total of 27 patients were randomized (18 restricted, 9 standard). Age, gender, ethnicity, past medical history, and body mass index were similar. American Society of Anesthesiologists class was somewhat higher in the restricted group (American Society of Anesthesiologists class 3 in 77% of restricted vs 44% of standard patients; P = 0.194). Median total intraoperative fluids were less in the restricted group (1300 mL) when compared with the standard group (3014 mL) (P = 0.021). Total fluids for the hospitalization were also statistically significantly decreased in the restricted group. Complications occurred in about two-thirds of patients, and complication rates were not statistically different between groups (1.6/restricted patient vs 2.1/standard patient; P = 0.333). Primary indications for boluses (n = 93) given to study patients were: hypotension (69%); oliguria (15%); and tachycardia (14%), with multiple indications per bolus. In only two instances did the StO2 drop to less than 75 per cent, or decrease by 20 per cent from baseline in the 3 minutes before bolus as an indication for fluid administration. Patients undergoing elective colorectal surgery with a fluid restricted strategy had only rare episodes of decreased StO2, suggesting that adequate tissue perfusion was maintained in this group. As a result, NIRS monitoring did not significantly influence intraoperative fluid management of patients undergoing colorectal surgery.

  View details for Web of Science ID 000285489300012

  View details for PubMedID 21265353

• Learning management systems and lecture capture in the medical academic environment. International anesthesiology clinics Chu, L. F., Young, C. A., Ngai, L. K., Cun, T., Pearl, R. G., Macario, A. 2010; 48 (3): 27-51

  Abstract

  As residents work disparate schedules at multiple locations and because of workweek hour limits mandated by the ACGME, residents may be unable to attend lectures, seminars, or other activities that would enhance their skills. Further, the ACGME requires that residency programs document resident learning in six stated core competencies and provide proof of completion for various other requirements. LMS/LC is a promising technology to provide a means by which residency programs may overcome these obstacles. More studies are needed to show under what conditions an LMS/LC program actually enhances learning, and which elements are most useful to the new generation of learners comfortable with Web 2.0 technologies.

  View details for DOI 10.1097/AIA.0b013e3181e5c1d5

  View details for PubMedID 20616636

• Learning Management Systems and Lecture Capture in the Medical Academic Environment INTERNATIONAL ANESTHESIOLOGY CLINICS Chu, L. F., Young, C. A., Ngai, L. K., Cun, T., Pearl, R. G., Macario, A. 2010; 48 (3): 27–51

  View details for DOI 10.1097/AIA.0b013e3181e5c1d5

  View details for Web of Science ID 000218297800004

• Anesthesia for patients with pulmonary hypertension CURRENT OPINION IN ANESTHESIOLOGY Pritts, C. D., Pearl, R. G. 2010; 23 (3): 411-416

  Abstract

  Patients with pulmonary hypertension who undergo anesthesia and surgery have high morbidity and mortality. Recent advances in our understanding of pulmonary hypertension and its therapy provide an opportunity to improve outcomes.Pulmonary hypertension can be classified into several subtypes, each with its own causes, pathophysiology, and therapy. Echocardiography remains a critical aspect of the evaluation of patients with pulmonary hypertension, but estimation of right ventricular systolic pressure is often inaccurate. Inhaled vasodilators can produce selective and potent pulmonary vasodilation.The cause of pulmonary hypertension should be defined in perioperative patients with pulmonary hypertension, and therapy should be optimized prior to anesthesia. Pulmonary artery catheterization may be required to confirm the presence of pulmonary hypertension and its severity. The focus of anesthetic management is to maintain right ventricular cardiac output and avoid systemic hypotension. Inhaled vasodilators such as nitric oxide and prostacyclin can be life-saving when perioperative right heart failure occurs due to exacerbation of pulmonary hypertension.

  View details for DOI 10.1097/ACO.0b013e32833953fb

  View details for Web of Science ID 000278004800020

  View details for PubMedID 20386437

• Adoption of anesthesia information management systems by academic departments in the United States ANESTHESIA AND ANALGESIA Halbeis, C. B., Epstein, R. H., Macario, A., Pearl, R. G., Grunwald, Z. 2008; 107 (4): 1323-1329

  Abstract

  Information technology has been promoted as a way to improve patient care and outcomes. Whereas information technology systems for ancillary hospital services (e.g., radiology, pharmacy) are deployed commonly, it has been estimated that anesthesia information management systems (AIMS) are only installed in a small fraction of United States (US) operating rooms. In this study, we assessed the adoption of AIMS at academic anesthesia departments and explored the motivations for and resistance to AIMS adoption.Members of the Society of Academic Anesthesiology Chairs and the Association of Anesthesiology Program Directors were solicited by e-mail to participate in an online survey of AIMS adoption. Two months after closing the survey, another e-mail was sent with a single question asking for an update to their AIMS implementation status.Surveys were fully completed by 48 (34%) of the 140 Society of Academic Anesthesiology Chairs and Association of Anesthesiology Program Directors departments surveyed, with 72 (51%) providing AIMS status information. Twenty of these 72 departments have an AIMS installed, 12 are currently implementing, 11 have selected but not yet installed, and 18 are planning to purchase an AIMS in 2008 or 2009. Therefore, at least 61 (44%) of all 140 US academic anesthesia departments have committed to AIMS. This estimated adoption rate is conservative because the numerator equals the affirmative responses, whereas the denominator equals the total population of academic departments. Among adopters, the top ranked anticipated benefits from installing an AIMS included improved clinical documentation, improved data collection for clinical research, enhancement of quality improvement programs, and compliance with requirements of regulatory authorities. The hospital provided funding in almost all facilities (90%), with co-funding by the anesthesia group in 35%.At least 61 or 44% of the 140 US academic departments surveyed in this study have already implemented, are planning to acquire, or are currently searching for an AIMS. Adoption of AIMS technology appears to have reached sufficient momentum within academic anesthesiology departments to result in a fundamental change.

  View details for DOI 10.1213/ane.0b013e31818322d2

  View details for Web of Science ID 000259522100042

  View details for PubMedID 18806048

• Training attendings to be expert teachers: the Stanford Anesthesia Teaching Scholars Program JOURNAL OF CLINICAL ANESTHESIA Macario, A., Edler, A., Pearl, R. 2008; 20 (3): 241-242

  View details for DOI 10.1016/j.jclinane.2008.01.002

  View details for Web of Science ID 000256730800021

  View details for PubMedID 18502376

• Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis NATURE MEDICINE Piliponsky, A. M., Chen, C., Nishimura, T., Metz, M., Rios, E. J., Dobner, P. R., Wada, E., Wada, K., Zacharias, S., Mohanasundaram, U. M., Faix, J. D., Abrink, M., Pejler, G., Pearl, R. G., Tsai, M., Galli, S. J. 2008; 14 (4): 392-398

  Abstract

  Sepsis is a complex, incompletely understood and often fatal disorder, typically accompanied by hypotension, that is considered to represent a dysregulated host response to infection. Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension. We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe cecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, show reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP.

  View details for DOI 10.1038/nm1738

  View details for Web of Science ID 000254674100025

  View details for PubMedID 18376408

  View details for PubMedCentralID PMC2873870

• Efficacy and safety of epoetin alfa in critically ill patients NEW ENGLAND JOURNAL OF MEDICINE Corwin, H. L., Gettinger, A., Fabian, T. C., May, A., Pearl, R. G., Heard, S., An, R., Bowers, P. J., Burton, P., Klausner, M. A., Corwin, M. J. 2007; 357 (10): 965-976

  Abstract

  Anemia, which is common in the critically ill, is often treated with red-cell transfusions, which are associated with poor clinical outcomes. We hypothesized that therapy with recombinant human erythropoietin (epoetin alfa) might reduce the need for red-cell transfusions.In this prospective, randomized, placebo-controlled trial, we enrolled 1460 medical, surgical, or trauma patients between 48 and 96 hours after admission to the intensive care unit. Epoetin alfa (40,000 U) or placebo was administered weekly, for a maximum of 3 weeks; patients were followed for 140 days. The primary end point was the percentage of patients who received a red-cell transfusion. Secondary end points were the number of red-cell units transfused, mortality, and the change in hemoglobin concentration from baseline.As compared with the use of placebo, epoetin alfa therapy did not result in a decrease in either the number of patients who received a red-cell transfusion (relative risk for the epoetin alfa group vs. the placebo group, 0.95; 95% confidence interval [CI], 0.85 to 1.06) or the mean (+/-SD) number of red-cell units transfused (4.5+/-4.6 units in the epoetin alfa group and 4.3+/-4.8 units in the placebo group, P=0.42). However, the hemoglobin concentration at day 29 increased more in the epoetin alfa group than in the placebo group (1.6+/-2.0 g per deciliter vs. 1.2+/-1.8 g per deciliter, P<0.001). Mortality tended to be lower at day 29 among patients receiving epoetin alfa (adjusted hazard ratio, 0.79; 95% CI, 0.56 to 1.10); this effect was also seen in prespecified analyses in those with a diagnosis of trauma (adjusted hazard ratio, 0.37; 95% CI, 0.19 to 0.72). A similar pattern was seen at day 140 (adjusted hazard ratio, 0.86; 95% CI, 0.65 to 1.13), particularly in those with trauma (adjusted hazard ratio, 0.40; 95% CI, 0.23 to 0.69). As compared with placebo, epoetin alfa was associated with a significant increase in the incidence of thrombotic events (hazard ratio, 1.41; 95% CI, 1.06 to 1.86).The use of epoetin alfa does not reduce the incidence of red-cell transfusion among critically ill patients, but it may reduce mortality in patients with trauma. Treatment with epoetin alfa is associated with an increase in the incidence of thrombotic events. (ClinicalTrials.gov number, NCT00091910 [ClinicalTrials.gov].).

  View details for Web of Science ID 000249210800003

  View details for PubMedID 17804841

• Thrombin-activatable fibrinolysis inhibitor (TAFI) regulates activated complement C5a in vivo. 46th Annual Meeting of the American-Society-of-Hematology Nishimura, T., Myles, T., Nagashima, M., MORSER, J., Pearl, R. G., Leung, L. L. AMER SOC HEMATOLOGY. 2004: 812A–812A

  View details for Web of Science ID 000225127502974

• Extended evaluation of recombinant human activated protein C United States trial (ENHANCE US) - A single-arm, phase 313, multicenter study of drotrecogin alfa (activated) in severe sepsis CHEST Bernard, G. R., Margolis, B. D., Shanies, H. M., Ely, E. W., Wheeler, A. P., Levy, H., Wong, K., Wright, T. J., Ahmed, M., Albertson, T., Anas, N., Astiz, M., Bacon, A., Bandi, V., Booth, F., Bray, W., Brilli, R., Carlson, R., Cheatham, M., Conrad, S., Cooney, R., Cox, M., Dolich, M., Dries, D., Fang, R., Forse, R., Fricker, R., Givens, C., Gomez, C., Gottlieb, J., Graham, D., Cropper, I., Cross, T., Harrison, N., Kearl, R., Kearney, P., Kinasewitz, G., Kruse, J., Lamberti, J., Levy, M., Light, R., Lin, L., Lisco, S., Lo, T., Linda, L., Lodato, R., Malave, L., Martinez, A., Mastuschak, G., Mcdermott, L., McFeely, P., Morris, P., Mueller, D., Naum, C., Neff, M., Niederman, M., Ost, D., Otoshi, J., Pearl, R., Pingleton, S., Player, R., Riker, R., Rodriguez, W., Rubeiz, G., Rumbak, M., Samuel, J., Santomauro, E., John, R. S., Seneff, M., Siegel, M., Siever, J., Sioson, P., Stasek, J., Steingrub, J., Taylor, J., Taylor, R., Turner, J., Verville, T., Waxman, K., Weiss, S., Wunderink, R., Wright, P. 2004; 125 (6): 2206-2216

  View details for Web of Science ID 000222253100040

• Longitudinal transcriptional analysis of developing neointimal vascular occlusion and pulmonary hypertension in rats PHYSIOLOGICAL GENOMICS Vaszar, L. T., Nishimura, T., Storey, J. D., Zhao, G. H., Qiu, D. M., Faul, J. L., Pearl, R. G., Kao, P. N. 2004; 17 (2): 150-156

  Abstract

  Pneumonectomized rats injected with the alkaloid toxin, monocrotaline, develop progressive neointimal pulmonary vascular obliteration and pulmonary hypertension resulting in right ventricular failure and death. The antiproliferative immunosuppressant, triptolide, attenuates neointimal formation and pulmonary hypertension in this disease model (Faul JL, Nishimura T, Berry GJ, Benson GV, Pearl RG, and Kao PN. Am J Respir Crit Care Med 162: 2252-2258, 2000). Pneumonectomized rats, injected with monocrotaline on day 7, were killed at days 14, 21, 28, and 35 for measurements of physiology and gene expression patterns. These data were compared with pneumonectomized, monocrotaline-injected animals that received triptolide from day 5 to day 35. The hypothesis was tested that a group of functionally related genes would be significantly coexpressed during the development of disease and downregulated in response to treatment. Transcriptional analysis using total lung RNA was performed on replicate animals for each experimental time point with exploratory data analysis followed by statistical significance analysis. Marked, statistically significant increases in proteases (particularly derived from mast cells) were noted that parallel the development of vascular obliteration and pulmonary hypertension. Mast-cell-derived proteases may play a role in regulating the development of neointimal pulmonary vascular occlusion and pulmonary hypertension in response to injury.

  View details for DOI 10.1152/physiolgenomics.00198.2003

  View details for PubMedID 15082832

• The CRIT Study: Anemia and blood transfusion in the critically ill - Current clinical practice in the United States CRITICAL CARE MEDICINE Corwin, H. L., Gettinger, A., Pearl, R. G., Fink, M. P., Levy, M. M., Abraham, E., MacIntyre, N. R., Shabot, M., Duh, M. S., Shapiro, M. J. 2004; 32 (1): 39-52

  Abstract

  To quantify the incidence of anemia and red blood cell (RBC) transfusion practice in critically ill patients and to examine the relationship of anemia and RBC transfusion to clinical outcomes.Prospective, multiple center, observational cohort study of intensive care unit (ICU) patients in the United States. Enrollment period was from August 2000 to April 2001. Patients were enrolled within 48 hrs of ICU admission. Patient follow-up was for 30 days, hospital discharge, or death, whichever occurred first.A total of 284 ICUs (medical, surgical, or medical-surgical) in 213 hospitals participated in the study.A total of 4,892 patients were enrolled in the study.The mean hemoglobin level at baseline was 11.0 +/- 2.4 g/dL. Hemoglobin level decreased throughout the duration of the study. Overall, 44% of patients received one or more RBC units while in the ICU (mean, 4.6 +/- 4.9 units). The mean pretransfusion hemoglobin was 8.6 +/- 1.7 g/dL. The mean time to first ICU transfusion was 2.3 +/- 3.7 days. More RBC transfusions were given in study week 1; however, in subsequent weeks, subjects received one to two RBC units per week while in the ICU. The number of RBC transfusions a patient received during the study was independently associated with longer ICU and hospital lengths of stay and an increase in mortality. Patients who received transfusions also had more total complications and were more likely to experience a complication. Baseline hemoglobin was related to the number of RBC transfusions, but it was not an independent predictor of length of stay or mortality. However, a nadir hemoglobin level of <9 g/dL was a predictor of increased mortality and length of stay.Anemia is common in the critically ill and results in a large number of RBC transfusions. Transfusion practice has changed little during the past decade. The number of RBC units transfused is an independent predictor of worse clinical outcome.

  View details for DOI 10.1097/01.CCM.00001104112.34142.79

  View details for Web of Science ID 000188318800005

  View details for PubMedID 14707558

• Thrombin activatable fibrinolysis inhibitor, a potential regulator of vascular inflammation JOURNAL OF BIOLOGICAL CHEMISTRY Myles, T., Nishimura, T., Yun, T. H., Nagashima, M., MORSER, J., Patterson, A. J., Pearl, R. G., Leung, L. L. 2003; 278 (51): 51059-51067

  Abstract

  The latent plasma carboxypeptidase thrombin-activable fibrinolysis inhibitor (TAFI) is activated by thrombin/thrombomodulin on the endothelial cell surface, and functions in dampening fibrinolysis. In this study, we examined the effect of activated TAFI (TAFIa) in modulating the proinflammatory functions of bradykinin, complement C5a, and thrombin-cleaved osteopontin. Hydrolysis of bradykinin and C5a and thrombin-cleaved osteopontin peptides by TAFIa was as efficient as that of plasmin-cleaved fibrin peptides, indicating that these are also good substrates for TAFIa. Plasma carboxypeptidase N, generally regarded as the physiological regulator of kinins, was much less efficient than TAFIa. TAFIa abrogated C5a-induced neutrophil activation in vitro. Jurkat cell adhesion to osteopontin was markedly enhanced by thrombin cleavage of osteopontin. This was abolished by TAFIa treatment due to the removal of the C-terminal Arg168 by TAFIa from the exposed SVVYGLR alpha 4 beta 1 integrin-binding site in thrombin-cleaved osteopontin. Thus, thrombin cleavage of osteopontin followed by TAFIa treatment may sequentially up- and down-modulate the pro-inflammatory properties of osteopontin. An engineered anticoagulant thrombin, E229K, was able to activate endogenous plasma TAFI in mice, and E229K thrombin infusion effectively blocked bradykinin-induced hypotension in wild-type, but not in TAFI-deficient, mice in vivo. Our data suggest that TAFIa may have a broad anti-inflammatory role, and its function is not restricted to fibrinolysis.

  View details for DOI 10.1074/jbc.M306977200

  View details for Web of Science ID 000187206300029

  View details for PubMedID 14525995

• Overview of anemia and blood management in critical care CRITICAL CARE MEDICINE Pearl, R. G., Sibbald, W. J. 2003; 31 (12): S649–S650

  View details for DOI 10.1097/00003246-200312001-00001

  View details for Web of Science ID 000187636200001

  View details for PubMedID 14724461

• Simvastatin rescues rats from fatal pulmonary hypertension by inducing apoptosis of neointimal smooth muscle cells CIRCULATION Nishimura, T., Vaszar, L. T., Faul, J. L., Zhao, G. H., Berry, G. J., Shi, L. F., Qiu, D. M., Benson, G., Pearl, R. G., Kao, P. N. 2003; 108 (13): 1640-1645

  Abstract

  Pulmonary vascular injury by toxins can induce neointimal formation, pulmonary arterial hypertension (PAH), right ventricular failure, and death. We showed previously that simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in pneumonectomized rats injected with the alkaloid toxin monocrotaline. The present study was undertaken to investigate the efficacy of simvastatin and its mechanism of reversing established neointimal vascular occlusion and pulmonary hypertension.Pneumonectomized rats injected with monocrotaline at 4 weeks demonstrated severe PAH at 11 weeks (mean pulmonary artery pressure [mPAP]=42 versus 17 mm Hg in normal rats) and death by 15 weeks. When rats with severe PAH received simvastatin (2 mg x kg(-1) x d(-1) by gavage) from week 11, there was 100% survival and reversal of PAH after 2 weeks (mPAP=36 mm Hg) and 6 weeks (mPAP=24 mm Hg) of therapy. Simvastatin treatment reduced right ventricular hypertrophy and reduced proliferation and increased apoptosis of pathological smooth muscle cells in the neointima and medial walls of pulmonary arteries. Longitudinal transcriptional profiling revealed that simvastatin downregulated the inflammatory genes fos, jun, and tumor necrosis factor-alpha and upregulated the cell cycle inhibitor p27Kip1, endothelial nitric oxide synthase, and bone morphogenetic protein receptor type 1a.Simvastatin reverses pulmonary arterial neointimal formation and PAH after toxic injury.

  View details for DOI 10.1161/01.CIR.0000087592.47401.37

  View details for PubMedID 12963647

• Anemia and blood transfusion in trauma patients admitted to the intensive care unit JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE Shapiro, M. J., Gettinger, A., Corwin, H. L., Napolitano, L., Levy, M., Abraham, E., Fink, M. P., MacIntyre, N., Pearl, R. G., Shabot, M. M. 2003; 55 (2): 269-273

  Abstract

  Anemia is a common occurrence in the intensive care unit (ICU). Although resuscitation, including the use of blood, is a mainstay of early treatment of trauma victims, the safety and efficacy of red blood cell (RBC) transfusion has come under scrutiny recently. The issue of blood use in critically injured patients requires evaluation.This was a post hoc analysis of a subset of trauma patients (> or =18 years in age) from a prospective, multicenter, observational, cohort study in the United States. Patients were enrolled within 48 hours after ICU admission and followed for up to 30 days, or until hospital discharge or death.Five hundred seventy-six patients from 111 ICUs in 100 hospitals were enrolled between August 2000 and April 2001. At baseline, mean age was 44.1 +/- 20.2 years, 73.6% were men, and mean APACHE II score was 16.9 +/- 8.2. Mean baseline hemoglobin was 11.1 +/- 2.4 g/dL and patients remained anemic throughout the study either with or without transfusion; 55.4% of patients were transfused (mean, 5.8 +/- 5.5 units) during the ICU stay and 43.8% of patients had an ICU length of stay > or = 7 days. Mean pretransfusion hemoglobin was 8.9 +/- 1.8 g/dL. Mean age of RBCs transfused was 20.1 +/- 11.4 days. As compared with the full study population, patients in the trauma subset were more likely to be transfused and received an average of 1 additional unit of blood.Anemia is common in critically injured trauma patients and persists throughout the duration of critical illness. These patients receive a large number of RBC transfusions during their ICU course with aged blood.

  View details for DOI 10.1097/01.T.A.0000080530.77566.04

  View details for Web of Science ID 000184906000015

  View details for PubMedID 12913636

• Effect of a surgical aortocaval fistula on mono crotaline-induced pulmonary hypertension CRITICAL CARE MEDICINE Nishimura, T., Faul, J. L., Berry, G. J., Kao, P. N., Pearl, R. G. 2003; 31 (4): 1213-1218

  Abstract

  Increased pulmonary blood flow is believed to contribute to the development of pulmonary hypertension. We investigated the effect of overcirculation via an aortocaval fistula, on the development of monocrotaline-induced pulmonary hypertension in rats. Monocrotaline was administered 1 wk after the creation of an aortocaval fistula.Randomized, controlled study.Research laboratory of an academic institution.Male Sprague-Dawley rats.Overcirculation was induced by pneumonectomy and by surgical creation of aortocaval fistula. Pulmonary artery hypertension was induced by administration of monocrotaline.Aortic blood flow, Pao(2), and pulmonary arterial pressure were measured 4 wks later. A blinded investigator quantified pulmonary arterial neointimal formation in small pulmonary arteries. Compared with animals that received monocrotaline and/or underwent pneumonectomy but did not undergo aortocaval fistula, the presence of a surgical aortocaval fistula was associated with increased aortic blood flow (p <.001), increased Pao(2) (p <.001), and lower mean pulmonary arterial pressure (p <.001). In addition, rats with aortocaval fistula had less pulmonary arterial neointimal formation than matched animals without an aortocaval fistula (p =.034).The presence of a surgical aortocaval fistula attenuates, rather than worsens, the development of monocrotaline-induced pulmonary hypertension in rats.

  View details for DOI 10.1097/01.CCM.0000059440.44597.07

  View details for PubMedID 12682495

• Efficacy of recombinant human erythropoietin in critically ill patients - A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Corwin, H. L., Gettinger, A., Pearl, R. G., Fink, M. P., Levy, M. M., Shapiro, M. J., Corwin, M. J., Colton, T. 2002; 288 (22): 2827-2835

  Abstract

  Anemia is common in critically ill patients and results in a large number of red blood cell (RBC) transfusions. Recent data have raised the concern that RBC transfusions may be associated with worse clinical outcomes in some patients.To assess the efficacy in critically ill patients of a weekly dosing schedule of recombinant human erythropoietin (rHuEPO) to decrease the occurrence of RBC transfusion.A prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted between December 1998 and June 2001.A medical, surgical, or a medical/surgical intensive care unit (ICU) in each of 65 participating institutions in the United States.A total of 1302 patients who had been in the ICU for 2 days and were expected to be in the ICU at least 2 more days and who met eligibility criteria were enrolled in the study; 650 patients were randomized to rHuEPO and 652 to placebo.Study drug (40 000 units of rHuEPO) or placebo was administered by subcutaneous injection on ICU day 3 and continued weekly for patients who remained in the hospital, for a total of 3 doses. Patients in the ICU on study day 21 received a fourth dose.The primary efficacy end point was transfusion independence, assessed by comparing the percentage of patients in each treatment group who received any RBC transfusion between study days 1 and 28. Secondary efficacy end points identified prospectively included cumulative RBC units transfused per patient through study day 28; cumulative mortality through study day 28; change in hemoglobin from baseline; and time to first transfusion or death.Patients receiving rHuEPO were less likely to undergo transfusion (60.4% placebo vs 50.5% rHuEPO; P<.001; odds ratio, 0.67; 95% confidence interval [CI], 0.54-0.83). There was a 19% reduction in the total units of RBCs transfused in the rHuEPO group (1963 units for placebo vs 1590 units for rHuEPO) and reduction in RBC units transfused per day alive (ratio of transfusion rates, 0.81; 95% CI, 0.79-0.83; P =.04). Increase in hemoglobin from baseline to study end was greater in the rHuEPO group (mean [SD], 1.32 [2] g/dL vs 0.94 [1.9] g/dL; P<.001). Mortality (14% for rHuEPO and 15% for placebo) and adverse clinical events were not significantly different.In critically ill patients, weekly administration of 40 000 units of rHuEPO reduces allogeneic RBC transfusion and increases hemoglobin. Further study is needed to determine whether this reduction in RBC transfusion results in improved clinical outcomes.

  View details for Web of Science ID 000179732600027

  View details for PubMedID 12472324

• Understanding and managing anemia in critically ill patients. Critical care nurse Pearl, R. G., Pohlman, A. 2002: 1-12

  Abstract

  Although anemia is apparently tolerated in most patients, particularly those who are relatively healthy, the ICU population must be thought of differently. Anemia in the ICU may be due to acute blood loss, phlebotomy, or to the presence of inflammatory disease. The anemia in critically ill patients resembles anemia of chronic disease, which is believed to result from a poor endogenous erythropoietin response or erythropoietin deficiency. The risks of blood transfusions are many and ICU patients may not tolerate infusions of older, stored blood. Nonetheless, hemoglobin levels at or above 100 g/L may be important for oxygen delivery to vital organs, especially in critically ill patients with increased oxygen demands. The appropriate transfusion trigger for critically ill patients in this setting remains unknown. Blood transfusions in the ICU may not improve outcomes, and numerous studies have been published to suggest the contrary, that transfusions may actually worsen patients' outcomes in certain ICU settings. Recombinant human erythropoietin (rHuEPO, epoetin alfa) has been shown to reduce transfusion needs and increase hemoglobin levels in multiple settings and now, it appears to also do so in the ICU.

  View details for PubMedID 12518573

• Simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in rats AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Nishimura, T., Faul, J. L., Berry, G. J., Vaszar, L. T., Qiu, D. M., Pearl, R. G., Kao, P. N. 2002; 166 (10): 1403-1408

  Abstract

  Hypertensive pulmonary vascular disease is characterized by abnormal proliferation of vascular endothelial and smooth muscle cells, leading to occlusion of pulmonary arterioles, pulmonary hypertension, right ventricular failure, and death. Compounds with antiproliferative effects on vascular endothelial and smooth muscle cells, such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, may prevent the development of experimental hypertensive pulmonary vascular disease. Pneumonectomized rats injected with monocrotaline at 7 days develop severe hypertensive pulmonary vascular disease with neointimal formation. Rats were randomized to receive either vehicle or treatment with the HMG-CoA reductase inhibitor simvastatin (2 mg/kg per day). By Day 35, rats that received vehicle had higher mean pulmonary arterial pressures (53 +/- 2 mm Hg) and right ventricular hypertrophy (right ventricle/[left ventricle plus septum] [RV/LV+S] = 0.78 +/- 0.09) than rats in Group PMS5-35 that received simvastatin from Day 5 to 35 (mean pulmonary arterial pressure = 27 +/- 3 mm Hg, RV/LV+S = 0.34 +/- 0.08; p < or = 0.001). Pulmonary vascular remodeling with neointimal formation consisting of vascular smooth muscle cells was more severe in vehicle-treated rats (vascular occlusion score, 1.98 +/- 0.02) than in Group PMS5-35 (vascular occlusion score, 0.59 +/- 0.46; p < 0.001). In addition, lung endothelial nitric oxide synthase gene expression was decreased in vehicle-treated animals but was restored toward normal levels in simvastatin-treated animals. Simvastatin attenuates monocrotaline-induced pulmonary vascular remodeling with neointimal formation, pulmonary arterial hypertension, and right ventricular hypertrophy in rats.

  View details for DOI 10.1164/rccm.200203-268OC

  View details for PubMedID 12406854

• The airway: emergent management for nonanesthesiologists WESTERN JOURNAL OF MEDICINE Fowler, R. A., Pearl, R. G. 2002; 176 (1): 45-50

  View details for Web of Science ID 000173085600018

  View details for PubMedID 11788539

• Clinical guidelines for the treatment of ventilator-associated pneumonia CRITICAL CARE MEDICINE Fowler, R. A. 2002; 30 (1): 266-266

  View details for Web of Science ID 000173409400050

  View details for PubMedID 11902284

• Improved technique for fascial sling reconstruction of severe congenital ptosis PLASTIC AND RECONSTRUCTIVE SURGERY Pearl, R. M. 2001; 107 (4): 1059-1059

  View details for Web of Science ID 000167551600023

  View details for PubMedID 11252103

• Nutritional deficiencies and blunted erythropoietin response as causes of the anemia of critical illness JOURNAL OF CRITICAL CARE Rodriquez, R. M., Corwin, H. L., Gettinger, A., Corwin, M. J., Gubler, D., Pearl, R. G. 2001; 16 (1): 36-41

  Abstract

  The purpose of this article was to determine the prevalence of iron, vitamin B12, and folate deficiency and to evaluate the erythropoietin (EPO) response to anemia in a cohort of long-term intensive care unit (ICU) patients.All patients admitted to three academic medical center multidisciplinary ICUs were screened for eligibility into a randomized trial of EPO for the treatment of ICU anemia. On their second or third ICU day, patients enrolled in this trial had EPO levels drawn and were screened for iron, B12, and folate deficiency. Weekly EPO levels were obtained throughout patients' ICU stay.A total of 184 patients were screened for iron, B12, and folate deficiency. Sixteen patients (9%) were iron deficient by study criteria, 4 (2%) were B12 deficient, and 4 (2%) were folate deficient. Mean hemoglobin and reticulocyte percents of the remaining 160 patients were 10.3 +/- 1.2 g/dL and 1.66 +/- 1.09%, respectively. In most patients, serum iron and total iron binding capacity levels were very low, whereas ferritin levels were very high. Mean and median day 2 EPO levels were 35.2 +/- 35.6 mIU/mL and 22.7 mIU/mL, respectively (normal = 4.2-27.8). Serial EPO levels in most persistently anemic patients remained within the normal range.In this cohort, screening for iron, B12, and folate deficiency identified potentially correctable abnormalities in more than 13% of patients and should be considered in those who are anticipated to have long ICU stays. Even at an early point of critical illness, most patients had iron studies consistent with anemia of chronic disease (ACD), as well as a blunted EPO response that may contribute to this ACD-like anemia of critical illness.

  View details for DOI 10.1053/jcrc.2001.21795

  View details for Web of Science ID 000167325400006

  View details for PubMedID 11230723

• 40-O-(2-hydroxyethyl)-rapamycin attenuates pulmonary arterial hypertension and neointimal formation in rats AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Nishimura, T., Faul, J. L., Berry, G. I., Veve, I., Pearl, R. G., Kao, P. N. 2001; 163 (2): 498-502

  Abstract

  Pneumonectomized rats develop pulmonary hypertension (PH) and pulmonary vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/kg/d, by gavage): Group PMR(5-35) from Day 5 to Day 35, Group PMR5-14 from Day 5 to Day 14, and Group PMR15-35 from Day 15 to Day 35. By Day 35, rats that received vehicle had higher mean pulmonary arterial pressures (Ppa = 41 +/- 3 mm Hg) (p < 0.001), right ventricular systolic pressures (Prv,s = 45 +/- 2 mm Hg) (p < 0.01), and right ventricle/(left ventricle plus septum) (0.55 +/- 0.05) (p = 0.028) than rats in Groups PMR5-35 (Ppa = 25 +/- 3 mm Hg, Prv,s = 32 +/- 7 mm Hg, RV/LV&S = 0.42 +/- 0.06) and PMR5-14 (Ppa = 29 +/- 4 mm Hg, Prv,s = 30 +/- 5 mm Hg, RV/LV&S = 0.43 +/- 0.07). Pulmonary arterial neointimal formation (quantified by a vascular occlusion score) was more severe in vehicle-treated rats (1.93 +/- 0.03) than in Groups PMR5-14 (1.56 +/- 0.27) and PMR(5-35) (1.57 +/- 0.1) (p < 0.01). RAD attenuates the development of MCT-induced pulmonary arterial hypertension in the pneumonectomized rat.

  View details for Web of Science ID 000167050900038

  View details for PubMedID 11179130

• Triptolide attenuates pulmonary arterial hypertension and neointimal formation in rats AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Faul, J. L., Nishimura, T., Berry, G. J., BENSON, G. V., Pearl, R. G., Kao, P. N. 2000; 162 (6): 2252-2258

  Abstract

  This paper reports the effect of triptolide (a diterpenoid triepoxide) on the development of monocrotaline (MCT)-induced pulmonary hypertension in pneumonectomized rats. Male Sprague- Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Rats received therapy from Day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day, n = 10), or vehicle (0.1 ml of ethanol/cremophor intraperitoneally, every other day, n = 10). By Day 35, triptolide-treated rats demonstrated lower mean pulmonary arterial pressure (mPAP) than vehicle-treated rats (mPAP 21 +/- 3 versus 42 +/- 5 mm Hg, p < 0.001). Triptolide-treated rats also had significantly less right ventricular hypertrophy (RVH) and pulmonary arterial neointimal formation. In a rescue experiment, rats initiated therapy on Day 21. At Day 35, vehicle-treated rats (n = 4) had higher mPAP (40 +/- 9 mm Hg), greater RVH, and more severe pulmonary arterial neointimal formation than rats that received triptolide (0.25 mg/kg every other day, n = 7, mPAP 30 +/- 4 mm Hg) and rats that received triptolide (0.2 mg/kg daily, n = 7, mPAP 25 +/- 5 mm Hg, p < 0.01). In pneumonectomized rats that receive MCT, triptolide attenuates the development of pulmonary hypertension and RVH, and promotes regression of pulmonary arterial neointimal formation.

  View details for Web of Science ID 000165794700050

  View details for PubMedID 11112148

• Combination therapy with inhaled nitric oxide and intravenous dobutamine during pulmonary hypertension in the rabbit JOURNAL OF CARDIOVASCULAR PHARMACOLOGY Bradford, K. K., Deb, B., Pearl, R. G. 2000; 36 (2): 146-151

  Abstract

  Combination therapy with an intravenous inovasodilator and inhaled nitric oxide (NO) may be appropriate in patients with pulmonary hypertension and associated right ventricular failure. We examined whether dobutamine and inhaled NO would have additive pulmonary vasodilator effects in experimental pulmonary hypertension. Pulmonary hypertension was produced in anesthetized, mechanically ventilated rabbits by infusion of U46619, a thromboxane analogue. Dobutamine was administered in increasing doses (2.5-20 microg/kg/min) with and without inhaled NO (40 ppm). Dobutamine produced dose-dependent decreases in pulmonary vascular resistance (PVR) and mean arterial pressure (MAP) and increases in cardiac output (CO). Inhaled NO alone decreased pulmonary artery pressure (PAP) and PVR with no effect on MAP or CO. The effects of dobutamine and inhaled NO were additive, so that at each dose of dobutamine, inhaled NO decreased PAP and PVR with no effect on systemic hemodynamics. This study suggests that the combination of dobutamine and inhaled NO should produce additive pulmonary vasodilation in patients with pulmonary hypertension and associated right ventricular dysfunction.

  View details for Web of Science ID 000088459900002

  View details for PubMedID 10942154

• Combined therapy with zaprinast and inhaled nitric oxide abolishes hypoxic pulmonary hypertension CRITICAL CARE MEDICINE Nagamine, J., Hill, L. L., Pearl, R. G. 2000; 28 (7): 2420-2424

  Abstract

  To determine whether the combination of the phosphodiesterase 5 inhibitor zaprinast and inhaled nitric oxide (NO) decreases hypoxic pulmonary hypertension in the rat.Prospective, experimental study.Animal laboratory of a university medical center.Male Sprague-Dawley rats.Anesthetized rats were mechanically ventilated and instrumented for measurement of mean systemic arterial pressure, pulmonary arterial pressure, and cardiac output. In group 1, four acute hypoxic challenges (FIO2 = 0.17 for 5 mins) were performed: initial, during 40 ppm inhaled NO, immediately after discontinuation of 5 mins of inhaled NO, and final. In group 2 rats, an initial hypoxic challenge was performed and rats then received zaprinast (3 mg/kg bolus followed by 0.3 mg/kg/min infusion). Four hypoxic challenges analogous to group 1 were then performed during zaprinast administration.Initial hypoxic challenge produced similar increases in pulmonary arterial pressure in both groups. In group 1, inhaled NO either only before or only during hypoxia decreased the pulmonary hypertensive response to hypoxia. In group 2, zaprinast administration did not alter hemodynamics. Zaprinast alone decreased the pulmonary hypertensive response to hypoxia. The combination of zaprinast and inhaled NO (either before or during hypoxia) abolished the pulmonary hypertensive response to hypoxia.Treatment with inhaled NO for 5 mins before but not during hypoxia is as effective as inhaled NO during hypoxia. Inhaled NO and zaprinast both decrease the pulmonary hypertensive response to hypoxia, and the combination abolishes the response. The combination of a phosphodiesterase 5 inhibitor and inhaled NO may have clinical applicability in the treatment of pulmonary hypertension.

  View details for Web of Science ID 000088315300035

  View details for PubMedID 10921573

• Additive effects of inhaled nitric oxide and intravenous milrinone in experimental pulmonary hypertension CRITICAL CARE MEDICINE Deb, B., Bradford, K., Pearl, R. G. 2000; 28 (3): 795-799

  Abstract

  To determine whether inhaled nitric oxide (IN0) and intravenous milrinone have additive pulmonary vasodilator effects in a rat model of pulmonary hypertension.Prospective, experimental study.Animal laboratory of a university medical center.Male New Zealand White rabbits.Anesthetized rabbits were mechanically ventilated and instrumented for measurement of systemic mean arterial pressure (MAP), pulmonary artery pressure (PAP), left atrial pressure, and cardiac output (CO). After baseline measurements, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg iv) was administered. Pulmonary hypertension was produced by the continuous infusion of U46619, a thromboxane A2 mimetic. INO (40 ppm) was added to the inspired gas, and hemodynamic measurements were obtained before and after INO. Milrinone was administered sequentially as a 30-mg/kg bolus followed by a 3-microg/kg/min infusion, a 100-mg/kg bolus followed by a 10-microg/kg/min infusion, and a 300-mg/kg bolus followed by a 30-microg/kg/min infusion (M3). Hemodynamic measurements were obtained with and without INO at each dose of milrinone.During U46619-induced pulmonary hypertension, INO decreased PAP and pulmonary vascular resistance (PVR) but did not affect MAP, systemic vascular resistance (SVR), or CO. Milrinone dose dependently decreased PAP, PVR, MAP, and SVR and increased CO. At each dose of milrinone, INO further decreased PVR but not SVR. M3 decreased PVR 49%, and the addition of INO decreased PVR an additional 19% so that PAP and PVR decreased to baseline values.Milrinone and INO both decrease pulmonary hypertension individually, and the combination produces additive effects. Combination therapy may produce potent and selective pulmonary vasodilation during the treatment of pulmonary hypertension.

  View details for Web of Science ID 000086051500031

  View details for PubMedID 10752832

• Sonic vibrational analysis provides continuous measurement of arterial properties JOURNAL OF CLINICAL MONITORING AND COMPUTING Rodriguez, R. M., Sher, M. H., Beringer, K. A., Caro, R. G., Pearl, R. G. 2000; 16 (7): 501-508

  Abstract

  We describe a new technology for measuring artery mechanical properties, called Sonic Vibrational Analysis (SVA). We utilize SVA to study the changes in radial artery smooth muscle tone caused by intravenous infusion of vasoactive agents.Six healthy volunteers were monitored with a radial intra-arterial catheter and an SVA sensor during progressively increasing doses of nitroglycerin (NTG), phenylephrine, sodium nitroprusside (SNP), dobutamine, and nicardipine. In SVA, the propagation velocity of an audio-frequency vibration is measured over a short segment of the radial artery. The measurement has sufficient temporal resolution to track the continuous changes in arterial properties that occur due to the natural blood pressure pulse.Coupled with the measurement of radial blood pressure, SVA allowed determination of the physiological/mechanical state of the artery within a single cardiac cycle. NTG, SNP, and phenylephrine caused significant changes in both blood pressure and the physiological state of the radial artery. Nicardipine and dobutamine altered blood pressure without change in the state of the radial artery.The current results are consistent with previous studies of the effects of vasoactive agents on the radial artery. SVA is non-invasive, continuous, localized to a well-defined section of artery, and suitable for the collection of large volumes of time-resolved data in a laboratory or clinical setting.

  View details for Web of Science ID 000169741400006

  View details for PubMedID 12580209

• Inhaled nitric oxide and pulmonary vasoreactivity JOURNAL OF CLINICAL MONITORING AND COMPUTING Aranda, M., Pearl, R. G. 2000; 16 (5-6): 393-401

  Abstract

  Inhaled nitric oxide is a ubiquitous molecule which is produced endogenously and is also found in air pollution and in cigarette smoke. After describing the chemistry of NO, we review its history from the first description in 1980 to the current clinical indications. The biosynthesis of NO, its effects on pulmonary vasoreactivity, and the administration of inhaled NO will be described. The indications, uses, and side effects of inhaled NO are discussed with an emphasis on withdrawal of NO therapy, specifically the "rebound" phenomenon. Possible drug interactions are listed. Inhaled nitric oxide is here to stay, and future studies will provide more information on its therapeutic dose, duration and potential toxicity.

  View details for Web of Science ID 000168535300008

  View details for PubMedID 12580222

• Efficacy of recombinant human erythropoietin in the critically ill patient: A randomized, double-blind, placebo-controlled trial CRITICAL CARE MEDICINE Corwin, H. L., Gettinger, A., Rodriguez, R. M., Pearl, R. G., Gubler, K. D., Enny, G., Colton, T., Corwin, M. J. 1999; 27 (11): 2346-2350

  Abstract

  To determine whether the administration of recombinant human erythropoietin (rHuEPO) to critically ill patients in the intensive care unit (ICU) would reduce the number of red blood cell (RBC) transfusions required.A prospective, randomized, double-blind, placebo-controlled, multicenter trial.ICUs at three academic tertiary care medical centers.A total of 160 patients who were admitted to the ICU and met the eligibility criteria were enrolled in the study (80 into the rHuEPO group; 80 into the placebo group).Patients were randomized to receive either rHuEPO or placebo. The study drug (300 units/kg of rHuEPO or placebo) was administered by subcutaneous injection beginning ICU day 3 and continuing daily for a total of 5 days (until ICU day 7). The subsequent dosing schedule was every other day to achieve a hematocrit (Hct) concentration of >38%. The study drug was given for a minimum of 2 wks or until ICU discharge (for subjects with ICU lengths of stay >2 wks) up to a total of 6 wks (42 days) postrandomization.The cumulative number of units of RBCs transfused was significantly less in the rHuEPO group than in the placebo group (p<.002, Kolmogorov-Smirnov test). The rHuEPO group was transfused with a total of 166 units of RBCs vs. 305 units of RBCs transfused in the placebo group. The final Hct concentration of the rHuEPO patients was significantly greater than the final Hct concentration of placebo patients (35.1+/-5.6 vs. 31.6+/-4.1; p<.01, respectively). A total of 45% of patients in the rHuEPO group received a blood transfusion between days 8 and 42 or died before study day 42 compared with 55% of patients in the placebo group (relative risk, 0.8; 95% confidence interval, 0.6, 1.1). There were no significant differences between the two groups either in mortality or in the frequency of adverse events.The administration of rHuEPO to critically ill patients is effective in raising their Hct concentrations and in reducing the total number of units of RBCs they require.

  View details for Web of Science ID 000083814800003

  View details for PubMedID 10579246

• Combined therapy with inhaled nitric oxide and intravenous vasodilators during acute and chronic experimental pulmonary hypertension ANESTHESIA AND ANALGESIA ARANDA, M., Bradford, K. K., Pearl, R. G. 1999; 89 (1): 152-158

  Abstract

  Both inhaled nitric oxide (NO) and IV vasodilators decrease pulmonary hypertension, but the effects of combination therapy are unknown. We studied the response to inhaled NO (100 ppm) alone, IV vasodilator alone, and combined therapy during acute (U46619-induced) and chronic (monocrotaline-induced) pulmonary hypertension in the pentobarbital-anesthetized rat. Vasodilator doses were 1.0, 3.2, 10, and 32 microg x kg(-1) x min(-1) sodium nitroprusside (SNP); 50, 100, 150, 200, and 300 microg x kg(-1) x min(-1) adenosine; or 25, 50, 150, 200, and 300 ng x kg(-1) x min(-1) prostacyclin. In the absence of IV vasodilator therapy, inhaled NO decreased mean pulmonary artery pressure without decreasing mean systemic arterial pressure. In both acute and chronic pulmonary hypertension, the addition of inhaled NO to the largest dose of adenosine or prostacyclin, but not of SNP, decreased pulmonary artery pressure. Because inhaled NO and SNP activate guanylyl cyclase and adenosine and prostacyclin activate adenylyl cyclase, the results suggest that adding inhaled NO to a vasodilator not dependent on guanylyl cyclase may produce additional selective pulmonary vasodilation.In therapy of pulmonary hypertension, inhaled nitric oxide should produce additional selective pulmonary vasodilation when combined with a vasodilator whose mechanism of action is not dependent on cyclic guanosine 3',5'-monophosphate.

  View details for Web of Science ID 000081101100027

  View details for PubMedID 10389795

• Inhaled nitric oxide potentiates actions of adenosine but not of sodium nitroprusside in experimental pulmonary hypertension PHARMACOLOGY Patterson, K. W., Deb, B., Kavanagh, B. P., Pearl, R. G. 1999; 58 (5): 246-251

  Abstract

  Inhaled nitric oxide (NO), a selective pulmonary vasodilator, increases intracellular cyclic guanosine monophosphate. In contrast, adenosine, another selective pulmonary vasodilator, increases intracellular cyclic adenosine monophosphate. There has been only limited study on effects of inhaled NO combined with other pulmonary vasodilators. The current study examined the hypothesis that inhaled NO would potentiate in vivo pulmonary vasodilator effects of adenosine, but not those of sodium nitroprusside (SNP). Like inhaled NO, SNP acts via cyclic guanosine monophosphate. Rabbits were anesthetized and mechanically ventilated. The NO synthesis inhibitor NG-nitro-L-arginine methyl ester was administered. U46619, a thromboxane A2 mimetic, was infused to produce pulmonary hypertension. Rabbits then received either SNP at doses of 0.5, 1, 2, 4, 8, 16, and 32 microg/kg/min or adenosine at doses of 12.5, 25, 50, 100, 150, and 300 microg/kg/min. Hemodynamic measurements were obtained with or without inhaled NO (40 ppm) at each dose of SNP or adenosine. During U46619-induced pulmonary hypertension, inhaled NO decreased pulmonary artery pressure and pulmonary vascular resistance. Adenosine and SNP produced dose-related decreases in pulmonary artery pressure and pulmonary vascular resistance and increases in cardiac output. Inhaled NO decreased pulmonary artery pressure and pulmonary vascular resistance at all doses of adenosine, but had no significant pulmonary vasodilator effects at doses of SNP >0.5 microg/kg/min. We conclude that inhaled NO does not produce additional pulmonary vasodilation over that achieved at higher doses of SNP, but does produce additional vasodilation when combined with a vasodilator having different mechanisms of action. Since both inhaled NO and adenosine produce selective pulmonary vasodilation, such combination therapy may be effective in patients with pulmonary hypertension.

  View details for Web of Science ID 000079720700003

  View details for PubMedID 10087465

• Combined inhaled nitric oxide and inhaled prostacyclin during experimental chronic pulmonary hypertension JOURNAL OF APPLIED PHYSIOLOGY Hill, L. L., Pearl, R. G. 1999; 86 (4): 1160-1164

  Abstract

  Inhaled nitric oxide (NO) and inhaled prostacyclin (PGI2) produce selective reductions in pulmonary vascular resistance (PVR) through differing mechanisms. NO decreases PVR via cGMP, and PGI2 produces pulmonary vasodilation via cAMP. As a general pharmacological principle, two drugs that produce similar effects via different mechanisms should have additive or synergistic effects when combined. We designed this study to investigate whether combined inhaled NO and PGI2 therapy results in additive effects during chronic pulmonary hypertension in the rat. Monocrotaline injected 4 wk before study produced pulmonary hypertension in all animals. Inhaled NO (20 parts/million) reversibly and selectively decreased pulmonary artery pressure (Ppa) with a mean reduction of 18%. Four concentrations of PGI2 were administered via inhalation (5, 10, 20, and 80 microg/ml), both alone and combined with inhaled NO. Inhaled PGI2 alone decreased Ppa in a dose-dependent manner with no change in mean systemic arterial pressure. Combined inhaled NO and PGI2 selectively and significantly decreased Ppa more did than either drug alone. The effects were additive at the lower concentrations of PGI2 (5, 10, and 20 microg/ml). The combination of inhaled NO and inhaled PGI2 may be useful in the management of pulmonary hypertension.

  View details for Web of Science ID 000080010200008

  View details for PubMedID 10194197

• Inhibition of endogenous nitric oxide synthesis potentiates the effects of sodium nitroprusside but not of adenosine in experimental pulmonary hypertension PHARMACOLOGY Wall, M. H., Patterson, K. W., Kavanagh, B. P., Pearl, R. G. 1999; 58 (1): 34-43

  Abstract

  This study examined the systemic and pulmonary vasodilator effects of sodium nitroprusside (SNP) and adenosine during experimental pulmonary hypertension with and without inhibition of endogenous NO synthesis. Male New Zealand White rabbits were anesthetized and mechanically ventilated. The NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was administered to 15 of the 28 rabbits. Pulmonary hypertension was then produced in all rabbits by U46619, a thromboxane A2 mimetic. SNP was infused in 14 rabbits (7 L-NAME, 7 control) at doses of 0.5-20 microg/kg/min; adenosine was infused in the other 14 rabbits (8 L- NAME, 6 control) at doses of 12.5-300 microg/kg/min. The U46619 dose required to produce pulmonary hypertension was significantly lower in the L-NAME group. SNP dose-dependently decreased pulmonary (Ppa) and systemic (Psa) artery pressures and systemic vascular resistance (SVR). Both Ppa and Psa were decreased more with SNP in the L-NAME than in the no L-NAME group. The SNP ED50 for the decrease in PVR was almost threefold lower in the L-NAME group. Adenosine dose-dependently decreased Ppa, Psa, PVR and SVR. The adenosine ED50 for the decreases in PVR and SVR were similar in the L-NAME group and the control group. We conclude that inhibition of endogenous NO synthesis shifts the dose-response curves for both the pulmonary and systemic vasodilator effects to the left for the nitrovasodilator SNP but not for the non-nitrovasodilator adenosine.

  View details for Web of Science ID 000077540200006

  View details for PubMedID 9831829

• Continuous cardiac output catheters - Delay in in vitro response time after controlled flow changes ANESTHESIOLOGY ARANDA, M., Mihm, F. G., Garrett, S., Mihm, M. N., Pearl, R. G. 1998; 89 (6): 1592-1595

  View details for Web of Science ID 000077376100046

  View details for PubMedID 9856744

• Pulmonary hypertension and major surgery ANESTHESIA AND ANALGESIA Rodriguez, R. M., Pearl, R. G. 1998; 87 (4): 812-815

  View details for Web of Science ID 000076234300013

  View details for PubMedID 9768775

• Prediction of poor outcome of intensive care unit patients admitted from the emergency department CRITICAL CARE MEDICINE Rodriguez, R. M., Wang, N. E., Pearl, R. G. 1997; 25 (11): 1801-1806

  Abstract

  To assess whether physicians can identify very low likelihood of survival and very low likelihood of favorable functional outcome in adult nontrauma patients before admission to the intensive care unit (ICU) from the emergency department (ED).Prospective survey.University hospital ED and ICU.Critical care fellows and ED physicians and all adult nontrauma patients admitted to the ICU from the ED over 1 yr.None.The survey compared predictions of poor outcome from three sources: critical care fellows, ED physicians, and the admission Mortality Probability Model (MPM0). All patients were followed until hospital death or hospital discharge. Six-month follow-up data were obtained for patients predicted to have a < 2% chance of surviving with favorable functional outcome. In the ED, critical care fellows and ED physicians predicted likelihood of patient survival and likelihood of favorable functional outcome. MPM0 estimates of mortality were determined. The sensitivities, specificities, and positive predictive values were calculated for the predictions of < 2% survival and the predictions of < 2% chance of favorable functional outcome made by each prediction group. Complete data were obtained on 236 (96%) of 243 eligible patients. With regard to hospital mortality rate, fellows' predictions had a sensitivity of 27%, a specificity of 99%, and a positive predictive value of 88%; ED physicians' predictions had a sensitivity of 24%, a specificity of 98%, and a positive predictive value of 81%; and MPM0 predictions had a sensitivity of 2%, a specificity of 100%, and a positive predictive value of 100%. With regard to mortality rate combined with poor functional outcome, fellows' predictions had a sensitivity of 35%, a specificity of 99%, and a positive predictive value of 96%; ED physicians' predictions had a sensitivity of 37%, a specificity of 99%, and a positive predictive value of 96%.If a cutoff point of < 2% predicted survival is used in the triage of patients away from the ICU, the MPM0 has too low a sensitivity to be used as an effective screen. The low sensitivities and relatively low positive predictive values with wide confidence intervals of physician predictions of < 2% survival also preclude their use in triage. The addition of functional outcome as an end point improves the sensitivity, specificity, and positive predictive value of subjective predictions, making triage of patients away from the ICU at the time of ED evaluation a realistic possibility.

  View details for Web of Science ID A1997YF16400016

  View details for PubMedID 9366761

• Combined therapy with inhaled nitric oxide and intravenous vasodilators during experimental pulmonary hypertension ARANDA, M., Kilroy, K., Pearl, R. G. LIPPINCOTT WILLIAMS & WILKINS. 1997: A1123–A1123

  View details for Web of Science ID A1997XV63601039

• Nitroglycerin does not alter pulmonary vascular permeability in isolated rabbit lungs 46th Annual Meeting of the American-Society-of-Anesthesiologists Thompson, J. S., Kavanagh, B. P., Pearl, R. G. LIPPINCOTT WILLIAMS & WILKINS. 1997: 359–62

  Abstract

  Nitroglycerin (NTG) produces vasodilation by releasing nitric oxide (NO) at the cellular level. Other studies have suggested that NO may directly alter vascular permeability and may alter the development of tissue injury. We therefore examined the effects of NTG on vascular permeability in the buffer-perfused rabbit lung under normal conditions and during lung injury. Vascular permeability was assessed by measurement of the capillary filtration coefficient (Kf,c). In normal lungs, NTG did not alter Kf,c or the rate of weight gain. Oxidant lung injury was produced by the addition of purine and xanthine oxidase and resulted in increased Kf,c and increased weight gain. However, NTG did not alter these effects of oxidant lung injury. We conclude that NTG does not alter pulmonary vascular permeability in either normal or oxidant-injured lungs.

  View details for Web of Science ID A1997WF15900022

  View details for PubMedID 9024029

• An economic analysis of health care reform and its implications for plastic surgery Annual Meeting of the American-Society-of-Plastic-and-Reconstructive-Surgeons Pearl, R. M., McAllister, H., PRUZANSKY, J. LIPPINCOTT WILLIAMS & WILKINS. 1997: 1–9

  View details for Web of Science ID A1997WA11700001

  View details for PubMedID 8982180

• Mechanical ventilation and adjuncts in acute respiratory distress syndrome INTERNATIONAL ANESTHESIOLOGY CLINICS Deb, B., Pearl, R. G. 1997; 35 (1): 109-124

  Abstract

  Acute respiratory distress syndrome is a response of the lung to both direct and indirect insults. Although much knowledge has been gained in understanding the pathophysiology of the syndrome, overall mortality in the past 25 years remains unchanged. Application of scientific knowledge to present-day technology has yielded advances in ventilator and pharmacological support for the patient with ARDS. Emphasis is now made on the prevention of iatrogenic lung injury with the use of pressure-limited mechanical ventilation, permissive hypercapnia, and artificial means of gas exchange (discussed in the chapter by Dr Furukawa). The role of INO and surfactant, as well as antimediator therapy, in the armamentarium against ARDS appears promising but awaits definitive clinical trials. Only with progress and newer therapies will we be able to improve the outlook for patients and families in the future.

  View details for Web of Science ID A1997WU04600008

  View details for PubMedID 9113524

• Delayed time response of the continuous cardiac output pulmonary artery catheter ANESTHESIA AND ANALGESIA Siegel, L. C., HENNESSY, M. M., Pearl, R. G. 1996; 83 (6): 1173-1177

  Abstract

  Previous studies of the accuracy of pulmonary artery catheters (PAC) which provide continuous cardiac output (CCO) monitoring have investigated the performance during steady-state conditions. We compared the response time to hemodynamic change using a CCO PAC and an ultrasonic flow probe (UFP). In five sheep, a CCO PAC was inserted, and an UFP for measurement of CCO was placed around the pulmonary artery via a left thoracotomy. Six interventions which rapidly alter cardiac output were studied: crystalloid bolus, balloon inflation in the inferior vena cava (IVC), IVC balloon deflation, dobutamine infusion, hemorrhage, and reinfusion of blood. Cardiac output measured before and after each intervention was used to calculate the total change caused by the intervention, and the time intervals from intervention to 20%, 50%, and 80% of that change were noted. For all interventions, the time response of CCO was significantly slower than UFP. The largest differences were seen with the rapid infusion of lactated Ringer's solution for which the time interval for 20% change was 7.3 +/- 2.3 min (mean +/- SD) for CCO versus 0.5 +/- 0.3 min for UFP. The time interval for 80% change was 14.5 +/- 4.1 min for CCO versus 1.8 +/- 0.9 min with UFP. The current study demonstrates clinically important time delays in the response of the CCO catheter. This delay must be considered when rapid alterations of the hemodynamic state may occur.

  View details for Web of Science ID A1996VV54300007

  View details for PubMedID 8942581

• Inhibition of endogenous nitric oxide synthase potentiates nitrovasodilators in experimental pulmonary hypertension American-Society-of-Anesthesiologists Annual Meeting Kavanagh, B. P., Thompson, J. S., Pearl, R. G. LIPPINCOTT WILLIAMS & WILKINS. 1996: 860–66

  Abstract

  The role of endogenous nitric oxide (NO) in the regulation of pulmonary vascular tone is complex. Inhibition of endogenous NO synthase, potentially through upregulation of guanylyl cyclase, results in an increase in potency of nitrovasodilators in the systemic circulation. This study considered whether inhibition of endogenous NO synthase would increase the potency of nitrovasodilators, but not of cyclic adenosine monophosphate-dependent vasodilators, in the pulmonary vasculature.We used the isolated buffer-perfused rabbit lung. Preparations were randomized to receive either pretreatment with NG-nitro-L-arginine methyl ester (or L-NAME, an inhibitor of endogenous NO synthase) or no pretreatment. Stable pulmonary hypertension was then produced by infusing the thromboxane A2 analog U46619. The dose-response characteristics of two nitrovasodilators, sodium nitroprusside and nitroglycerin, and two nonnitrovasodilators, prostaglandin E2 and 5'-N-ethylcarboxamidoadenosine, were studied.Inhibition of endogenous NO synthase caused no significant changes in baseline pulmonary artery pressure but did significantly reduce the U46619 infusion rate required to produce pulmonary hypertension. Pretreatment with L-NAME (vs. no L-NAME) resulted in significantly lower values of the log median effective dose with sodium nitroprusside and nitroglycerin. In contrast, pretreatment with L-NAME resulted in no changes in the dose-response characteristics of the cyclic adenosine monophosphate-mediated, NO-independent vasodilators prostaglandin E1 and 5'-N-ethylcarboxamidoadenosine.These data suggest that endogenous NO synthase is not an important regulator of basal pulmonary tone in this model but is an important modulator of pulmonary vascular responses to vasoconstriction and to nitrovasodilators. The pulmonary vasodilator effects of nitrovasodilators, but not of nonnitrovasodilators, may depend on the level of activity of NO synthase.

  View details for Web of Science ID A1996VM09800024

  View details for PubMedID 8873557

• Plasma potentiates the priming effects of endotoxin on platelet activating factor-induced pulmonary hypertension in the rabbit lung ANESTHESIA AND ANALGESIA Goldsmith, J. A., Kavanagh, B. P., Pearl, R. G. 1996; 83 (2): 242-246

  Abstract

  During Gram-negative sepsis, endotoxin lipopolysaccharide (LPS) may activate host inflammatory responses, resulting in the systemic inflammatory response syndrome and the adult respiratory distress syndrome. In cell culture systems, LPS activation of cellular responses may be potentiated by plasma proteins. In the isolated perfused rabbit lung, LPS administration markedly increases the pulmonary hypertensive response to subsequent administration of platelet activating factor (PAF). We examined whether plasma would potentiate the priming effects of LPS in this model. Male New Zealand White rabbits were used in a standard, isolated buffer-perfused rabbit lung preparation, and the pulmonary hypertensive response to 5 nM PAF was measured after 2 h of perfusion with different LPS doses (0, 1, and 10 ng/mL), with and without plasma (10% by volume). In the absence of plasma, 10 ng/mL LPS, but not 1 ng/mL LPS, increased the pulmonary hypertensive response to subsequent administration of 5 nM PAF. However, in the presence of plasma, 1 ng/mL LPS significantly increased the hypertensive response to subsequent administration of 5 nM PAF. We conclude that components of plasma--possibly LPS binding protein and soluble CD14--potentiate the priming effect of endotoxin, resulting in an augmented pulmonary hypertensive response to PAF. Thus, plasma proteins decrease the threshold at which endotoxin primes the lung and may have a critical role in the pathogenesis of endotoxin-induced acute lung injury.

  View details for Web of Science ID A1996UZ99100008

  View details for PubMedID 8694300

• PULMONARY CAPILLARY-PRESSURE MEASUREMENT FROM PULMONARY-ARTERY OCCLUSION PRESSURE DECAY PROFILE ANALYSIS IN SHEEP ANESTHESIA AND ANALGESIA WAKERLIN, G. E., Finn, J. C., Siegel, L. C., BENSON, G. V., Flavin, T. F., Pearl, R. G. 1995; 81 (1): 17-23

  Abstract

  Pulmonary capillary pressure (Ppc), the major factor responsible for pulmonary edema, cannot be directly measured in intact subjects but may be estimated by analysis of the pressure decay profile after pulmonary artery catheter balloon inflation. We compared three different methods of pulmonary artery occlusion pressure (Ppao) decay profile analysis to estimates of Ppc derived from lymph flow measurements in halothane-anesthesized sheep. The relationship between Ppc and lymph flow was first determined by increasing Ppc by left atrial balloon inflation, and was then used to determine Ppc during pulmonary hypertension produced by infusion of a thromboxane analog. All three methods of Ppao decay profile analysis demonstrated a correlation with Ppc estimated from lymph flow. However, the method using a single exponential analysis significantly overestimated Ppc, and none of the methods reliably estimated changes in the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension. These results suggest that Ppao decay profile analysis as currently performed has limited application.

  View details for Web of Science ID A1995RF82000004

  View details for PubMedID 7598249

• IMPROVED TECHNIQUE FOR FASCIAL SLING RECONSTRUCTION OF SEVERE CONGENITAL PTOSIS PLASTIC AND RECONSTRUCTIVE SURGERY Pearl, R. M. 1995; 95 (5): 920-923

  Abstract

  Fascial sling surgery for severe congenital ptosis yields superior results when the operative result is dynamic rather than merely suspensory. The sling itself is attached as in a tendon transfer solely to the frontalis muscle, minimizing adherence to the underlying periosteum and the overlying dermis. The sling is passed behind a pulley created by the superior transverse ligament so as to produce a more normal vector of pull. The dermis of the skin is attached to the sling to create a dynamic supratarsal crease. Postoperative retraining allows the patient to achieve more than one centimeter of levator function. These operative modifications make this procedure more closely parallel the normal eyelid dynamics and yield consistently good results for this difficult problem.

  View details for Web of Science ID A1995QP97900025

  View details for PubMedID 7708879

• EFFECT OF BLOOD AND ALBUMIN ON PULMONARY-HYPERTENSION AND EDEMA IN PERFUSED RABBIT LUNGS JOURNAL OF APPLIED PHYSIOLOGY KRAFT, S. A., Fujishima, S., McGuire, G. P., Thompson, J. S., Raffin, T. A., Pearl, R. G. 1995; 78 (2): 499-504

  Abstract

  Perfusate composition may alter pulmonary hemodynamics and edema formation in perfused lungs. Perfusion for 3 h with Krebs-Henseleit solution with 3% bovine serum albumin did not produce pulmonary hypertension, pulmonary edema (assessed by lung wet-to-dry wt ratio), or increased macromolecular permeability (assessed by 125I-albumin uptake). Addition of blood to hematocrit levels of 10 or 20% resulted in pulmonary hypertension during the final hour of perfusion but not pulmonary edema or increased macromolecular permeability. Pulmonary hypertension during blood perfusion was primarily due to increased precapillary resistance. Perfusion with buffer solution without albumin produced edema and increased macromolecular permeability but not pulmonary hypertension. In lungs perfused with blood (20% hematocrit), thromboxane B2 levels increased in parallel with the pulmonary hypertension, and inhibition of cyclooxygenase or thromboxane synthase with indomethacin or dazmegrel prevented pulmonary hypertension. Perfusion with leukopenic blood (from prior nitrogen mustard administration or from filtration) also prevented pulmonary hypertension. We conclude that blood perfusion produces pulmonary hypertension via thromboxane A2 generation, which depends on leukocyte activation, and that perfusion with buffer solutions without albumin produces edema and increased permeability without pulmonary hypertension.

  View details for Web of Science ID A1995QG47700018

  View details for PubMedID 7759418

• INHALED NITRIC-OXIDE IN ANESTHESIA AND CRITICAL CARE MEDICINE INTERNATIONAL ANESTHESIOLOGY CLINICS Kavanagh, B. P., Pearl, R. G. 1995; 33 (1): 181-210

  Abstract

  Inhaled NO is an exciting new drug and has enormous potential in the therapy of a wide variety of acute, and possibly chronic, cardiopulmonary disorders. No reports of controlled, randomized, and blinded trials have been published concerning the use of inhaled NO in any clinical condition. In the United States, use of inhaled NO currently requires an investigational new drug approval from the Food and Drug Administration. Physicians involved in anesthesia and critical care medicine have a unique opportunity to validate a new mode of therapy in acute care, and optimal evaluation should be undertaken so that the real therapeutic role of inhaled NO may be defined.

  View details for Web of Science ID A1995QX08000011

  View details for PubMedID 7635555

• INHALED NITRIC-OXIDE DOES NOT ALTER THE LONGITUDINAL DISTRIBUTION OF PULMONARY VASCULAR-RESISTANCE JOURNAL OF APPLIED PHYSIOLOGY LINDEBORG, D. M., Kavanagh, B. P., VANMEURS, K., Pearl, R. G. 1995; 78 (1): 341-348

  Abstract

  Because the effects of inhaled nitric oxide (NO) may be localized to its site of delivery, we studied the effects of inhaled NO on the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension in perfused rabbit lungs. Before NO administration, pulmonary hypertension was produced by infusion of the thromboxane A2 mimetic U-46619 in all lungs. Pulmonary vascular resistance was divided into arterial, microvascular, and venous components by arterial and venous occlusion techniques. In the buffer-perfused lung, all doses of inhaled NO (5, 20, and 80 ppm) produced small decreases (approximately 3 mmHg) in pulmonary arterial pressure (Ppa), with equivalent proportional reductions in all segmental vascular resistances. Similar results were obtained after an extended inhaled NO dose range of 20, 80, and 240 ppm. In the buffer-perfused lung, inhibition of endogenous NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME) potentiated the effects of U-46619. Subsequent inhaled NO administration produced larger decreases (approximately 7 mmHg) in Ppa with equivalent proportional reductions in all segmental vascular resistances. In the blood-perfused lung, L-NAME did not alter baseline pulmonary pressures. Administration of inhaled NO during U-46619-induced pulmonary hypertension produced dose-related decreases in Ppa. The highest dose (80 ppm) of inhaled NO decreased Ppa by 3.5 mmHg, with equivalent proportional reductions in all segmental vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1995QC30100049

  View details for PubMedID 7713835

• INHIBITION OF ENDOGENOUS NITRIC-OXIDE SYNTHASE POTENTIATES NITROVASODILATORS IN PULMONARY-HYPERTENSION Kavanagh, B. P., Thompson, J. S., Pearl, R. G. LIPPINCOTT WILLIAMS & WILKINS. 1994: A1492–A1492

  View details for Web of Science ID A1994PJ09101490

• SERUM BUT NOT PLASMA PRODUCES INJURY IN THE PERFUSED RABBIT LUNG ANESTHESIA AND ANALGESIA MOUCHAWAR, A. M., Kavanagh, B. P., Pearl, R. G. 1994; 79 (1): 40-45

  Abstract

  Serum contains proteins that may produce lung injury directly by affecting endothelial cells and indirectly by modulating the effects of endotoxin (lipopolysaccharide). We studied the effects of 10% serum, 10% plasma, and 10% plasma plus 2 micrograms/mL lipopolysaccharide on pulmonary hypertension and vascular permeability in the isolated perfused rabbit lung. Control lungs perfused with Krebs-Henseleit buffer containing 3% albumin for 2 h had stable pulmonary vascular pressures and permeability (measured by the capillary filtration coefficient). Serum produced pulmonary hypertension and increased pulmonary vascular permeability. In contrast, plasma, with and without lipopolysaccharide, did not alter pulmonary vascular pressures or permeability. Pretreatment with the cyclooxygenase inhibitor indomethacin prior to the addition of serum prevented the serum-induced increase in pulmonary vascular pressures and permeability. We conclude that the deleterious effects of serum are not due to plasma proteins per se, but instead are related to activation of the coagulation cascade during preparation of the serum. The deleterious effects of serum appear to be mediated by cyclooxygenase metabolites of arachidonic acid. Finally, endotoxin, even with the addition of plasma, does not directly produce lung injury.

  View details for Web of Science ID A1994NU61200009

  View details for PubMedID 8010452

• ADENOSINE PRODUCES PULMONARY VASODILATION IN THE PERFUSED RABBIT LUNG VIA AN ADENOSINE A(2) RECEPTOR ANESTHESIA AND ANALGESIA Pearl, R. G. 1994; 79 (1): 46-51

  Abstract

  Adenosine is a potent pulmonary vasodilator that has been used in therapy for clinical and experimental pulmonary hypertension. To determine the receptor responsible for adenosine-induced pulmonary vasodilation, we studied the relative potency of four adenosine agonists in the isolated buffer-perfused rabbit lung during pulmonary hypertension due to infusion of the thromboxane A2 mimetic U46619. The ED50 values for pulmonary vasodilation were 1.9 x 10(-8) mol/L for 5'-N-ethylcarboxamidoadenosine (NECA), 4.5 x 10(-8) mol/L for 2-phenylaminoadenosine (CV-1808), 2.6 x 10(-6) mol/L for R(-)-N6-(2-phenylisopropyl) adenosine (R-PIA), and 6.5 x 10(-6) mol/L for cyclopentyladenosine, results consistent with an adenosine A2 receptor. Pretreatment with the adenosine A1 receptor antagonist cyclopentyltheophylline did not affect the dose-response curve to NECA, and pretreatment with the adenosine A2 receptor antagonist CGS 15943A increased the ED50 of NECA to 2.7 x 10(-7) mol/L. These results suggest that adenosine produces pulmonary vasodilation via activation of an adenosine A2 receptor.

  View details for Web of Science ID A1994NU61200010

  View details for PubMedID 8010453

• EFFECTS OF L-GLUTAMINE ON PULMONARY-HYPERTENSION IN THE PERFUSED RABBIT LUNG PHARMACOLOGY Xu, H., Pearl, R. G. 1994; 48 (4): 260-264

  Abstract

  The effects of l-glutamine on pulmonary hypertension in the isolated perfused rabbit lung were investigated. Pulmonary hypertension was produced by the thromboxane-A2 mimetic U46619. l-Glutamine at a dose of 0.04 mM produced a sustained increase in pulmonary artery pressure (PAP) and subsequent administration of an equimolar dose of l-arginine did not affect PAP. l-Glutamine at a dose of 0.5 mM transiently increased PAP, which then decreased to baseline (pre-glutamine) values. When endogenous nitric oxide (NO) synthesis was inhibited with NG-nitro-l-arginine methylester, l-glutamine at a dose of 0.04 mM decreased PAP. These results demonstrate that the effect of l-glutamine on PAP during pulmonary hypertension depends upon dose, time and the presence of endogenous NO synthesis. We believe that the results can be explained by two different effects of l-glutamine, namely a direct inhibition of NO release by glutamine and the donation of nitrogen atoms by glutamine for additional NO or other vasodilator synthesis. Since plasma glutamine levels are 0.4-0.7 mM, endogenous l-glutamine may play a modulatory role during pulmonary hypertension.

  View details for Web of Science ID A1994NA63400008

  View details for PubMedID 8177911

• EFFECTS OF INHALED NO AND INHIBITION OF ENDOGENOUS NO SYNTHESIS IN OXIDANT-INDUCED ACUTE LUNG INJURY JOURNAL OF APPLIED PHYSIOLOGY Kavanagh, B. P., MOUCHAWAR, A., Goldsmith, J., Pearl, R. G. 1994; 76 (3): 1324-1329

  Abstract

  Inhaled nitric oxide (NO) decreases pulmonary arterial pressure (Ppa) and improves oxygenation in the adult respiratory distress syndrome. Endogenous NO can modulate the development of acute tissue injury. We investigated the effects of inhaled NO and of inhibition of endogenous NO synthase in oxidant-induced acute lung injury in the isolated buffer-perfused rabbit lung. A rapid (45 min) and a more gradual (3 h) model of oxidant-induced acute lung injury were developed using the production of superoxide free radicals from the reaction of purine with low and high doses of xanthine oxidase, respectively. The effects of rapid injury included increases in Ppa, precapillary pulmonary vascular resistance, capillary filtration coefficient (Kfc), and lung weight. In the gradual-injury model, only lung weight and Kfc increased. Pretreatment with inhaled NO (90-120 ppm) prevented the rise in Ppa and precapillary pulmonary vascular resistance in the rapid-injury model and prevented elevation of Kfc in the gradual-injury model. Pretreatment with an inhibitor of endogenous NO synthase (NG-nitro-L-arginine methyl ester) resulted in increased pulmonary capillary pressure and postcapillary pulmonary vascular resistance in the rapid-injury model and increased peak Ppa, pulmonary capillary pressure, and pulmonary vascular resistance in the gradual-injury model. These data suggest that in oxidant-induced acute lung injury 1) inhaled NO may attenuate increases in capillary permeability and 2) endogenous NO may function as a modulator of pulmonary vascular tone without affecting capillary permeability.

  View details for Web of Science ID A1994NB20400050

  View details for PubMedID 8005878

• CLINICAL USES OF PROSTAGLANDINS IN ANESTHESIA AND INTENSIVE-CARE MEDICINE BAILLIERES CLINICAL ANAESTHESIOLOGY Kavanagh, B. P., Pearl, R. G. 1994; 8 (1): 175-200

  View details for Web of Science ID A1994ND71100009

• EXTENSOR DIGITI-MINIMI TENDON TRANSFER TO PREVENT RECURRENT ULNAR DRIFT PLASTIC AND RECONSTRUCTIVE SURGERY Pearl, R. M., Hentz, V. R. 1993; 92 (3): 507-510

  Abstract

  Thirty percent of patients with rheumatoid arthritis develop ulnar drift. Although numerous operations have been described, recurrence of the deformity is frequent. We recommend use of the extensor digiti minimi tendon transfer to prevent recurrent ulnar deviation. The tendon insertion is moved from a dorsal location to a dorsal-radial position. In this new location, the tendon produces both extension and radial deviation. Moreover, this transfer is maximally effective in extension when ulnar drift is greatest. We have used this transfer 28 times during the past 6 years. In evaluating patients more than 1 year after surgery, metacarpal phalangeal joint extension averaged 52 degrees and there was no evidence of recurrent ulnar drift of the little finger. The only problem was slight hyperextension of less than 5 degrees in approximately half of the patients. However, in no patient was this functionally a problem. We recommend the use of this tendon transfer in all patients with ulnar drift undergoing metacarpal phalangeal joint replacement for rheumatoid arthritis.

  View details for Web of Science ID A1993LR60800020

  View details for PubMedID 8341752

• INOTROPIC THERAPY IN THE CRITICALLY ILL PATIENT INTERNATIONAL ANESTHESIOLOGY CLINICS LINDEBORG, D. M., Pearl, R. G. 1993; 31 (2): 49-71

  Abstract

  Inotropic support is an important therapeutic modality in the intensive care unit. There are three classes of agents available to the clinician: catecholamines, bipyridines, and cardiac glycosides. Each class increases inotropy by a different mechanism and each agent has distinct physiological and pharmacological actions. It is important to understand the underlying pathophysiology involved so the appropriate inotrope can be chosen on a rational basis. Prior to and during therapy invasive hemodynamic monitoring is required to ensure proper titration of the chosen agent. If an undesirable effect ensues, therapy can then be modified.

  View details for Web of Science ID A1993LF40900004

  View details for PubMedID 8314629

• PULMONARY CAPILLARY-PRESSURE MEASUREMENT DURING GLOBAL HYPOXIA IN SHEEP ANESTHESIA AND ANALGESIA Siegel, L. C., Pearl, R. G., August, D. A. 1993; 76 (1): 149-155

  Abstract

  Analysis of the pressure decay following pulmonary artery occlusion can be used to determine pulmonary capillary pressure and to calculate the magnitudes of the arterial and venous components of pulmonary vascular resistance. The separation of pulmonary vascular resistance into components has been termed "the longitudinal distribution of pulmonary vascular resistance" to emphasize the fact that different pressures occur at a number of sites in the pulmonary circulation. The longitudinal distribution of pulmonary vascular resistance is closely related to pulmonary capillary pressure. Several methods of data analysis have been proposed to determine pulmonary capillary pressure from the pressure decay following pulmonary artery occlusion. In this study, three methods of data analysis were applied to the model of hypoxic pulmonary vasoconstriction to evaluate the validity of the methodology in a well known model. Pulmonary artery occlusion pressure decay curves were obtained from eight halothane-anesthetized sheep during control conditions (FIO2 = 0.99) and during hypoxic ventilation (FIO2 = 0.14). Analysis of the pulmonary artery occlusion pressure decay curves indicated the following results: 1) Hypoxia increased mean pulmonary artery pressure by 105% and increased pulmonary vascular resistance by 149%; 2) the increase in the calculated arterial component of pulmonary vascular resistance accounted for 88% of the increase in pulmonary vascular resistance with hypoxia; and 3) hypoxia produced only a 1.0 mm Hg increase in pulmonary capillary pressure. These results are consistent with other evidence showing that hypoxia primarily produces precapillary pulmonary vasoconstriction and has little effect on pulmonary capillary pressure. Pulmonary artery occlusion pressure decay curve analysis appears to be a valid technique for the measurement of pulmonary capillary pressure during hypoxia in intact anesthetized animals.

  View details for Web of Science ID A1993KY03600025

  View details for PubMedID 8418716

• PULMONARY-ARTERY CATHETERIZATION - THE RIGHT HEART SHOULD NOT BE LEFT OUT - A CASE-REPORT ANGIOLOGY Cook, D. J., Davis, S. F., Barr, J. A., Pearl, R. G. 1992; 43 (11): 952-956

  Abstract

  Tricuspid valve stenosis in the setting of endocarditis is associated with a high morbidity. Diagnostic approaches incorporate a high clinical index of suspicion, echocardiographic evidence, and inferences about hemodynamic data derived from pulmonary artery catheterization. As demonstrated by the case presented herein, inadequate initial evaluation of right-sided pressures delayed the diagnosis and treatment of prosthetic tricuspid valve stenosis.

  View details for Web of Science ID A1992JX49800011

  View details for PubMedID 1443769

• BIGUANIDE-ASSOCIATED LACTIC-ACIDOSIS - CASE-REPORT AND REVIEW OF THE LITERATURE ARCHIVES OF INTERNAL MEDICINE Gan, S. C., Barr, J., Arieff, A. I., Pearl, R. G. 1992; 152 (11): 2333-2336

  Abstract

  The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis.We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia.Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital.Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.

  View details for Web of Science ID A1992JX15100023

  View details for PubMedID 1444694

• TREATMENT OF ENOPHTHALMOS CLINICS IN PLASTIC SURGERY Pearl, R. M. 1992; 19 (1): 99-111

  Abstract

  This article has focused on the prevention and treatment of enophthalmos. It has stressed that enophthalmos is both a common complication of orbital fracture and a complication that can be difficult to treat. The cause of these failures of primary and secondary treatment is failure to recognize that orbital fractures have two distinct patterns and that neither is secondary to the anterior orbital floor defect. The zygoma fracture is the more common fracture and the most frequent cause of late enophthalmos. When this bone fractures, it does so at its sutural attachments. It is essential to reposition it at a minimum of three locations to achieve correction in three dimensions. The key to adequate reduction is not only to identify the frontozygomatic and zygomaticomaxillary suture at the infraorbital rim, but also to examine the zygomaticomaxillary suture in the region of the anterior maxillary buttress. Frequently, reduction at the first two sutural areas still leaves persistent lateral rotation of the zygoma and marked intraorbital volumetric expansion behind the axis of the globe. Complete reduction at three points will prevent late enophthalmos. Reosteotomy with repositioning of the zygoma and bone grafting to restore proper orbital volume can correct secondary enophthalmos once it develops. True blow-out fractures do occur, but the cause of the enophthalmos is most commonly the concomitant medial wall fracture and the occasional posterior expansion. The key to treatment is proper diagnosis, which is dependent upon CT scanning. Following definition of the exact fracture spots, restoration of intraorbital volume and sealing of the defects are satisfactory to avoid enophthalmos.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1992LA24500009

  View details for PubMedID 1537231

• EFFECTS OF PROSTAGLANDIN-E1 AND HYDRALAZINE ON THE LONGITUDINAL DISTRIBUTION OF PULMONARY VASCULAR-RESISTANCE DURING VASOCONSTRICTOR PULMONARY-HYPERTENSION IN SHEEP ANESTHESIOLOGY Pearl, R. G., Siegel, L. C. 1992; 76 (1): 106-112

  Abstract

  Pulmonary capillary pressure (Ppc) is dependent upon left atrial pressure, pulmonary venous resistance, and cardiac output. The effects of pulmonary vasodilators on Ppc will therefore depend upon any alterations in the longitudinal distribution of pulmonary vascular resistance (precapillary [arterial] and postcapillary [venous] components). We therefore studied the effects of two pulmonary vasodilators (prostaglandin E1 and hydralazine) on Ppc and the longitudinal distribution of pulmonary vascular resistance. Pulmonary hypertension was produced in sheep by the continuous administration of the thromboxane A2-mimetic U46619. Ppc was measured by analysis of pulmonary artery occlusion pressure decay curves. U46619 increased Ppc by 9 mmHg and increased both the arterial and venous components of pulmonary vascular resistance. Subsequent administration of prostaglandin E1 decreased Ppc by 5 mmHg and decreased both the arterial and venous components of pulmonary vascular resistance (by 50 and 69% respectively). Hydralazine produced smaller decreases in the arterial and venous components of pulmonary vascular resistance (by 35 and 49% respectively) and did not significantly reduce Ppc. We conclude that prostaglandin E1 but not hydralazine is effective in decreasing Ppc in this experimental model of pulmonary hypertension.

  View details for Web of Science ID A1992GY98000016

  View details for PubMedID 1729914

• LONGITUDINAL DISTRIBUTION OF PULMONARY VASCULAR-RESISTANCE AFTER ENDOTOXIN ADMINISTRATION IN SHEEP CRITICAL CARE MEDICINE Pearl, R. G., BAER, E. R., Siegel, L. C., BENSON, G. V., Rice, S. A. 1992; 20 (1): 119-125

  Abstract

  Pulmonary hypertension may increase pulmonary capillary pressure and exacerbate pulmonary edema in acute respiratory failure. The effects of pulmonary hypertension on pulmonary capillary pressure depend on the longitudinal distribution of pulmonary vascular resistance. Since pulmonary hypertension occurs during acute respiratory failure, we hypothesized that acute respiratory failure may produce time-dependent changes in the longitudinal distribution of pulmonary vascular resistance. Therefore, we measured pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance in an animal model of acute respiratory failure. Escherichia coli endotoxin (2.5 to 5.0 micrograms/kg) was administered over a 1-hr period in eight anesthetized sheep. Pulmonary and systemic hemodynamics, including pulmonary artery occlusion pressure (PAOP), pulmonary capillary pressure, and the longitudinal distribution of pulmonary vascular resistance, were measured over the next 5 hrs. Pulmonary capillary pressure was estimated by analysis of the pressure decay following pulmonary artery balloon inflation.Endotoxin administration resulted in sustained pulmonary hypertension for the subsequent 5 hrs of the study. Pulmonary capillary pressure was increased 7 mm Hg above baseline at 0.5 and 0.75 hrs during the infusion of endotoxin but returned to baseline values at 1.5 hrs. Despite sustained pulmonary hypertension, pulmonary capillary pressure remained at baseline values for the duration of the study. Similar to pulmonary capillary pressure, pulmonary venous (or postcapillary) resistance was increased approximately four-fold over baseline at 0.5 and 0.75 hrs after initiating endotoxin administration, but returned to baseline values by the end of endotoxin administration and remained at baseline values throughout the remainder of the study. In contrast, pulmonary arterial (or precapillary) resistance remained at values approximately three times baseline during the infusion and throughout the duration of the study.In this experimental model of acute respiratory failure, the effects of endotoxin on the longitudinal distribution of pulmonary vascular resistance are time-dependent. If these data from animals can be extrapolated to humans, we speculate that the importance of pulmonary venoconstriction in exacerbating pulmonary edema may vary over time in patients with acute respiratory failure.

  View details for Web of Science ID A1992GZ01500024

  View details for PubMedID 1729029

• A THROMBOXANE ANALOG INCREASES PULMONARY CAPILLARY-PRESSURE BUT NOT PERMEABILITY IN THE PERFUSED RABBIT LUNG 1990 ANNUAL MEETING OF THE AMERICAN SOC OF ANESTHESIOLOGISTS WAKERLIN, G. E., BENSON, G. V., Pearl, R. G. LIPPINCOTT WILLIAMS & WILKINS. 1991: 475–80

  Abstract

  Thromboxane has been implicated as a mediator of pulmonary hypertension and pulmonary edema in acute respiratory failure. Pulmonary edema may result from increased pulmonary capillary hydrostatic pressure or from increased pulmonary vascular permeability. We therefore studied the effects of a stable thromboxane analog, U46619, on these two parameters in the perfused rabbit lung. Pulmonary capillary pressure was measured by the double vascular occlusion method, and pulmonary vascular permeability was estimated by measurement of the pulmonary fluid filtration coefficient (Kf). U46619 infusion produced pulmonary hypertension and lung weight gain; increased both the arterial (precapillary) and venous (postcapillary) components of pulmonary vascular resistance; and increased pulmonary capillary pressure from 4.7 +/- 0.5 to 9.0 +/- 0.7 mmHg (P less than 0.01). The isogravimetric pressure (equivalent to the capillary pressure corresponding to no lung weight gain) was 4.0 +/- 0.4 mmHg before U46619 and 4.6 +/- 0.4 mmHg during U46619. Therefore, U46619 significantly increased capillary pressure above isogravimetric pressure and resulted in the development of pulmonary edema. U46619 did not affect vascular permeability as measured by Kf. We conclude that pulmonary venoconstriction resulting in increased pulmonary capillary hydrostatic pressure is the major mechanism by which thromboxane produces pulmonary edema in isolated lungs.

  View details for Web of Science ID A1991GD69900015

  View details for PubMedID 1888055

• PATHOPHYSIOLOGY OF CLEFT-LIP MUSCLES FOLLOWING THE INITIAL SURGICAL REPAIR PLASTIC AND RECONSTRUCTIVE SURGERY Schendel, S. A., Pearl, R. M., DeArmond, S. J. 1991; 88 (2): 197-200

  Abstract

  Muscle biopsy specimens taken from the upper lip and perialar area during the time of secondary lip revision and studied by histochemical techniques demonstrate persistent connective-tissue and muscle abnormalities even at a distance from the cleft margins. Some of these changes are consistent with surgically induced denervation-reinnervation of muscle groups in the surgical field. Increased amounts of connective tissue also were found, most likely secondary to the original deformity and the subsequent surgical procedures. Both these changes may be important factors in subsequent abnormal growth and development of the underlying midfacial structures. This study also demonstrated the resolution of previously noted mitochondrial abnormalities found in the primary cleft lip patient.

  View details for Web of Science ID A1991FY79100003

  View details for PubMedID 1852810

• THERMODILUTION CARDIAC-OUTPUT MEASUREMENT WITH A LARGE LEFT-TO-RIGHT SHUNT JOURNAL OF CLINICAL MONITORING Pearl, R. G., Siegel, L. C. 1991; 7 (2): 146-153

  Abstract

  Cardiac output was measured by the thermodilution method in a patient with a left-to-right shunt undergoing cardiac catheterization. It appeared that the thermodilution method measured systemic rather than pulmonary blood flow. This occurred because of the slow injection of injectate in the presence of a large left-to-right shunt. Theoretical thermodilution cardiac output curves are provided to illustrate the interaction of these two factors when three different durations of injection and four different shunt sizes are used.

  View details for Web of Science ID A1991FH21600003

  View details for PubMedID 2072128

• TREATMENT OF EXOPHTHALMOS PLASTIC AND RECONSTRUCTIVE SURGERY Pearl, R. M., VISTNES, L., Troxel, S. 1991; 87 (2): 236-244

  Abstract

  Current procedures for Graves' exophthalmos fail to achieve complete correction. The standard orbital decompressions were therefore modified to maximize the degree of volumetric increase behind the axis of the globe. In 15 orbits, the preoperative exophthalmos averaged 9.5 mm, whereas the postoperative exophthalmos was 4.1 mm. Postoperative CT study demonstrated that the remaining posterior orbital wall, combined with the persistently increased intraocular muscle volume, blocked retrodisplacement of the globe, despite adequate total volumetric increase. The increased muscle volume varied from 2 to 5 cc. Despite this residual exophthalmos, the modified four-wall expansion provides excellent aesthetic results with visual improvement and resolution of chemosis and exposure keratitis.

  View details for Web of Science ID A1991EV35600004

  View details for PubMedID 1989015

• LEUKOTRIENE SYNTHESIS INHIBITION AND RECEPTOR BLOCKADE DO NOT INHIBIT HYPOXIC PULMONARY VASOCONSTRICTION IN SHEEP ANESTHESIA AND ANALGESIA Pearl, R. G., Prielipp, R. C. 1991; 72 (2): 169-176

  Abstract

  Several lines of evidence suggest that leukotrienes may be mediators of hypoxic pulmonary vasoconstriction (HPV). However, the effect of leukotriene inhibition on HPV remains controversial. The present study investigated the effect of leukotriene synthesis inhibition and receptor blockade on HPV in the halothane-anesthetized sheep. After initial baseline measurements, the pulmonary pressor response to 15 min of global hypoxia (FIO2 = 0.13) was measured. A second set of baseline measurements was obtained and the sheep then received the combined cyclooxygenase/lipoxygenase inhibitor BW755C, the selective lipoxygenase inhibitor U60257, or the leukotriene receptor antagonist LY171883. Hemodynamic measurements were obtained after drug administration and during a subsequent hypoxic challenge (FIO2 = 0.13). Initial hypoxic challenge increased pulmonary artery pressure 68% and increased pulmonary vascular resistance 104%. Pulmonary hemodynamics after recovery from hypoxia were similar to initial baseline values. Drug administration had no significant hemodynamic effect. Hypoxic challenge after drug administration resulted in a pulmonary pressor response identical to the initial hypoxic challenge. Because leukotriene synthesis inhibition and receptor blockade did not alter the response to hypoxia, we conclude that leukotrienes are not obligatory mediators of HPV. A critical review of the literature supports a modulatory rather than an obligatory role for leukotrienes in HPV.

  View details for Web of Science ID A1991EU71100005

  View details for PubMedID 1670754

• ISOPROTERENOL PREVENTS OXIDANT-INDUCED INJURY IN ISOLATED RABBIT LUNGS PHARMACOLOGY Fujishima, S., KRAFT, S. A., McGuire, G. P., Raffin, T., Pearl, R. G. 1991; 43 (2): 78-83

  Abstract

  Increased vascular permeability in the adult respiratory distress syndrome is due in part to toxic oxygen metabolites. In the present study, we produced lung injury in the isolated rabbit lung with hydrogen peroxide (H2O2) and examined its prevention with isoproterenol. Pulmonary arterial pressure (Ppa) and the fluid filtration coefficient (Kf) were measured as indices of lung injury. Rabbits were divided into two groups, and 7 mmol/l H2O2 was administered in both groups. In one group, isoproterenol (2 micrograms/ml) was administered 10 min before H2O2 injury. Ppa increased transiently after H2O2 administration in the control group but was unchanged in the isoproterenol group. Kf was significantly increased by H2O2 administration in the control group but not in the isoproterenol group. We conclude that H2O2 increases pulmonary vascular permeability and that isoproterenol may protect against H2O2-induced pulmonary injury.

  View details for Web of Science ID A1991GP44100004

  View details for PubMedID 1775513

• HEMODYNAMIC PROFILES OF PROSTAGLANDIN-E1, ISOPROTERENOL, PROSTACYCLIN, AND NIFEDIPINE IN EXPERIMENTAL PORCINE PULMONARY-HYPERTENSION CRITICAL CARE MEDICINE Prielipp, R. C., McLean, R., Rosenthal, M. H., Pearl, R. G. 1991; 19 (1): 60-67

  Abstract

  We compared the hemodynamic effects of four vasodilators in experimental embolic pulmonary hypertension in a randomized controlled trial, using nine pigs weighing 16 to 23 kg. After anesthesia induction and cannulation with arterial, central venous, and thermodilution output pulmonary artery catheters, animals were repetitively embolized with glass beads (60 to 160 mu) in order to establish pulmonary hypertension (pulmonary artery pressure [PAP] doubled from baseline). Prostaglandin E1 (PGE1), isoproterenol, prostacyclin (PGI2), and nifedipine were compared at doses producing equivalent reduction in systemic BP.Only PGE1 and PGI2 decreased both PAP and pulmonary vascular resistance (PVR). PGE1 decreased PAP from 39 +/- 1 to 33 +/- 1 mm Hg; prostacyclin decreased PAP from 38 +/- 1 to 31 +/- 1 mm Hg and produced the largest increase in cardiac output (Qt). Isoproterenol did not change PAP, markedly increased heart rate (162 +/- 8 to 216 +/- 11 beats/min), and resulted in significant arrhythmias. Nifedipine increased PVR from 1044 +/- 113 to 1125 +/- 100 dyne.sec.cm-5 and decreased Qt.Vasodilators demonstrate unique hemodynamic drug profiles. Isoproterenol infusion is characterized by tachycardia and arrhythmias. Both PGE1 and PGI2 effectively decrease PAP and PVR. Nifedipine depressed Qt significantly in this glass-bead embolization model of acute pulmonary hypertension.

  View details for Web of Science ID A1991EU89500015

  View details for PubMedID 1986891

• PULMONARY CAPILLARY PRESSURES DURING HYPOXIA AND HYPOXEMIA CRITICAL CARE MEDICINE Siegel, L. C., Pearl, R. G. 1990; 18 (12): 1493-1494

  View details for Web of Science ID A1990EL99000038

  View details for PubMedID 2245633

• HEMODYNAMIC-EFFECTS OF DILTIAZEM DURING VASOCONSTRICTOR PULMONARY-HYPERTENSION IN SHEEP ANESTHESIA AND ANALGESIA Pearl, R. G., Finn, J. C. 1990; 71 (5): 493-497

  Abstract

  Calcium channel blockers have been effective as pulmonary vasodilators in patients with pulmonary hypertension. The current study therefore compared the effects of prostaglandin E1, an effective pulmonary vasodilator, with the effects of the water-soluble calcium channel blocker diltiazem during pulmonary hypertension in sheep. Pulmonary hypertension was produced by continuous intravenous administration of U46619 to halothane-anesthetized sheep. Prostaglandin E1 decreased pulmonary artery pressure 29%, decreased pulmonary vascular resistance (Rp) 57%, and did not affect the ratio of pulmonary to systemic vascular resistance (Rp/Rs). Diltiazem decreased pulmonary artery pressure 15%, decreased Rp 50%, and did not affect Rp/Rs. When 0.33 mL/kg polyethylene glycol-ethanol vehicle (the vehicle used for nifedipine administration in a prior study) was administered during diltiazem infusion, pulmonary artery pressure increased 19%, Rp increased 72%, and Rp/Rs increased 29%. These results indicate that diltiazem is an effective pulmonary vasodilator and suggest that the previously reported unfavorable results of nifedipine may have been due to the vehicle used for nifedipine administration.

  View details for Web of Science ID A1990EE23400007

  View details for PubMedID 2221409

• PRESSURE MEASUREMENT ARTIFACT WITH ANALOG-TO-DIGITAL CONVERSION JOURNAL OF CLINICAL MONITORING Siegel, L. C., Pearl, R. G. 1990; 6 (4): 318-321

  Abstract

  Pressure was transduced with the use of a fluid-filled catheter and standard medical monitoring equipment. When the signal was sampled at 200 Hz with an analog-to-digital converter, an artifact was observed. The 3.5-Hz artifact had an amplitude of 0.3 to 0.9 mm Hg and was caused by aliasing of a noise contaminant from the 2,403.5-Hz electrical excitation signal of the transducer. The artifact was completely eliminated with a 100-Hz low-pass filter. Electrical filtering is necessary for accurate acquisition of pressure measurements with analog-to-digital conversion, even when the sampling rate satisfies the Nyquist criterion for the frequency response of the mechanical system. Although the impact of the artifact is small in the clinical area, it is important under some research circumstances.

  View details for Web of Science ID A1990EA95100008

  View details for PubMedID 2230860

• TREATMENT OF MANDIBULAR FRACTURE - A HYPOTHESIS ANNALS OF PLASTIC SURGERY Pearl, R. M. 1990; 25 (3): 236-237

  View details for Web of Science ID A1990DW85700017

  View details for PubMedID 2241046

• PREVENTION OF ENOPHTHALMOS - A HYPOTHESIS ANNALS OF PLASTIC SURGERY Pearl, R. M. 1990; 25 (2): 132-133

  View details for Web of Science ID A1990DT72300009

  View details for PubMedID 2204305

• THE ILIAC CREST CARTILAGINOUS CAP ANNALS OF PLASTIC SURGERY Schendel, S. A., Pearl, R. M. 1990; 25 (1): 29-31

  Abstract

  Bone and cartilage grafts can be procured from the ilium either separately or as composite chondroosseous grafts when sufficient cartilage is present. The thickness and anatomy of this iliac cartilaginous cap was analyzed in relationship to age in 50 individuals. Histology was that of normal hyaline cartilage. The cartilage alone was more pliable with little memory when compared with auricular or septal cartilage. The cartilage/bone junction was very strong. Cartilage thickness ran from close to 1 cm at age 5 to a diminished zero at age 25.

  View details for Web of Science ID A1990DN58200007

  View details for PubMedID 2378494

• CROMOLYN SODIUM DOES NOT INHIBIT HYPOXIC PULMONARY VASOCONSTRICTION IN SHEEP ANESTHESIA AND ANALGESIA Pearl, R. G. 1990; 71 (1): 83-87

  Abstract

  Cromolyn sodium has been reported to inhibit hypoxic pulmonary vasoconstriction (HPV) in dogs and sheep, presumably by stabilizing mast cell membranes and thereby preventing the release of mediators such as leukotrienes. Because the effects of leukotriene synthesis and receptor blockers on HPV have been variable across studies, we studied the effect of cromolyn on HPV in the halothane-anesthetized sheep, a model in which we have found leukotriene synthesis and receptor blockers to be ineffective. In control animals, hypoxia (FIO2 = 0.13) increased pulmonary artery pressure (Ppa) 67% and pulmonary vascular resistance 85%, and these responses were reproducible with a second episode of hypoxia. In a second group of sheep, hypoxia (FIO2 = 0.13) during cromolyn administration (6 mg.kg-1.min-1) for 30 min increased (Ppa) 104% and increased pulmonary vascular resistance 124%. In a third group of sheep, cromolyn sodium (6 mg.kg-1.min-1) without hypoxia did not significantly affect pulmonary hemodynamics. We conclude that cromolyn sodium does not inhibit HPV in halothane-anesthetized sheep. In experimental designs in which cromolyn does alter HPV, the effect is more likely due to altered release of modulators of HPV rather than to decreased release of obligatory mediator of HPV.

  View details for Web of Science ID A1990DK76300015

  View details for PubMedID 2114066

• VASODILATOR THERAPY IN MICROEMBOLIC PORCINE PULMONARY-HYPERTENSION ANESTHESIA AND ANALGESIA McLean, R. F., Prielipp, R. C., Rosenthal, M. H., Pearl, R. G. 1990; 71 (1): 35-41

  Abstract

  The hemodynamic effects of prostaglandin E1, sodium nitroprusside (SNP), nitroglycerin, and hydralazine were studied in a porcine model of elevated pulmonary vascular resistance (PVR) due to glass bead microembolization (60-150-microns diameter). Each animal received all four drugs. Each drug was titrated to produce a 30% reduction in mean systemic arterial pressure. Although all four drugs decreased PVR, distinct differences in the hemodynamic profiles of the four drugs were evident. Prostaglandin E1 produced the largest reduction in mean pulmonary artery pressure (from 41 +/- 1 to 32 +/- 9 mm Hg, mean +/- SEM) and PVR (25 +/- 3 to 18 +/- 2 mm Hg.L-1.min-1), and did not affect the ratio of PVR to systemic vascular resistance (PVR/SVR). Sodium nitroprusside and nitroglycerin produced moderate decreases in PVR (nitroglycerin 21 +/- 2 to 18 +/- 2 mm Hg.L-1.min-1, SNP 22 +/- 2 to 19 +/- 2 mm Hg.L-1.min-1) and in mean pulmonary artery pressure (nitroglycerin 39 +/- 1 to 35 +/- 1; SNP 40 +/- 1 to 36 +/- 2 mm Hg). Both drugs significantly increased the PVR/SVR ratio. Hydralazine was the only drug that significantly increased cardiac output (1.6 +/- 0.2 to 1.9 +/- 0.3 L/min). Hydralazine had no significant effect on mean pulmonary artery pressure, reduced PVR to the smallest extent (11%), and resulted in the largest increase in the PVR/SVR ratio (from 0.52 +/- 0.04 to 0.80 +/- 0.08). In this model of increased pulmonary vasculature resistance prostaglandin E1 caused an equivalent amount of pulmonary and systemic vasodilation, as expressed by the PVR/SVR ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1990DK76300006

  View details for PubMedID 2114065

• EFFECT OF HYPERGLYCEMIA ON NEURONAL CHANGES IN A RABBIT MODEL OF FOCAL CEREBRAL-ISCHEMIA STROKE KRAFT, S. A., Larson, C. P., Shuer, L. M., Steinberg, G. K., BENSON, G. V., Pearl, R. G. 1990; 21 (3): 447-450

  Abstract

  In clinical medicine, cerebral ischemia is frequently due to a focal, rather than global, insult. The effect of hyperglycemia in focal cerebral ischemia is not well defined. We studied the effect of hyperglycemia on neuropathologic changes in a rabbit model of focal cerebral ischemia. Rabbits were randomized to receive saline (n = 12) or glucose (n = 12) infusions. The left anterior cerebral and left internal carotid arteries were clipped after the infusion began. After 6 hours of occlusion, the area of severe ischemic neuronal damage in the left neocortex and striatum on two standard sections of brain was calculated and expressed as a percentage of the total area of the left cortex or striatum. The mean +/- SEM cortical area of severe ischemic neuronal damage was 22.1 +/- 2.8% in the glucose-treated rabbits and 34.0 +/- 4.6% in the saline-treated rabbits (p less than 0.05). The cortical area of severe ischemic neuronal damage was inversely correlated with plasma glucose concentration at the time of arterial clipping (p less than 0.05). We conclude that hyperglycemia is associated with decreased histologic neuronal injury in this model of focal cerebral ischemia and may be protective when cerebral ischemia occurs from a focal insult.

  View details for Web of Science ID A1990CT20500015

  View details for PubMedID 2309269

• A BETTER SKY HOOK FOR HAND ELEVATION ANNALS OF PLASTIC SURGERY Sunde, D., Pearl, R. 1990; 24 (2): 189-190

  View details for Web of Science ID A1990CQ22500017

  View details for PubMedID 2316979

• SEPSIS AND THE TRAUMA PATIENT CRITICAL CARE CLINICS McGuire, G. P., Pearl, R. G. 1990; 6 (1): 121-146

  Abstract

  Conventional therapy for septic shock concentrates on correcting circulatory perfusion defects by optimizing hemodynamic parameters and oxygen delivery to the periphery. In the face of ongoing sepsis, the central abnormality of nutrient acquisition and energy production at the cellular level remains and the patient often progresses to MSOF despite our best efforts. Currently, surgical drainage and antibiotic therapy are the mainstays for eradication of infection. In the future, as we understand more of the mediators and metabolic consequences of septic shock, we anticipate that a more specific, directed therapy will be developed to reduce the high mortality rate.

  View details for Web of Science ID A1990CJ20700011

  View details for PubMedID 2404543

• PROPYLENE-GLYCOL-INDUCED PULMONARY-HYPERTENSION IN SHEEP PHARMACOLOGY Pearl, R. G., Rice, S. A. 1989; 39 (6): 383-389

  Abstract

  Propylene glycol is commonly used as a vehicle for drug administration. In experiments involving the measurement of pulmonary hemodynamics, pentobarbital anesthesia routinely resulted in pulmonary hypertension in sheep. Since pentobarbital is formulated with 40% propylene glycol, we studied the pulmonary hemodynamic effects of propylene glycol in halothane-anesthetized sheep. Intravenous 40% propylene glycol (0.12 ml/kg over 3 min) rapidly increased pulmonary artery pressure (from 10 +/- 2 to 18 +/- 1 mm Hg; p less than 0.01) and pulmonary vascular resistance (from 200 +/- 18 to 500 +/- 51 dyn.s.cm-5; p less than 0.01); pulmonary hypertension was still present 1 h later. In sheep pretreated with the selective thromboxane A2 synthesis inhibitor dazmegrel, propylene glycol did not affect pulmonary artery pressure or pulmonary vascular resistance. Propylene-glycol-induced pulmonary hypertension in sheep appears to be mediated by thromboxane A2. Both ethanol and polyethylene glycol similarly produce pulmonary hypertension in sheep. We conclude that vehicle control data are required for studies using propylene glycol in sheep and advise caution when propylene glycol is employed as a vehicle in clinical use.

  View details for Web of Science ID A1989CU83000006

  View details for PubMedID 2634856

• A COMPARATIVE-ANALYSIS OF THE ABILITY OF 5 CLASSES OF PHARMACOLOGICAL AGENTS TO AUGMENT SKIN FLAP SURVIVAL IN VARIOUS MODELS AND SPECIES - AN ATTEMPT TO STANDARDIZE SKIN FLAP RESEARCH ANNALS OF PLASTIC SURGERY Waters, L. M., Pearl, R. M., MACAULAY, R. M. 1989; 23 (2): 117-122

  Abstract

  There is a myriad of research in the pharmacological manipulation of skin flap survival. However, skepticism exists as to whether any of these drugs is clinically useful. We evaluated the efficacy of five categories of agents in improving skin flap survival in five different rat flap models. Diltiazem, isoxsuprine hydrochloride, nitroglycerin, prazosin hydrochloride (two doses), and methyldopa were compared in a double-blind, randomized fashion. Their benefits were assessed in a musculocutaneous flap, axial flap, and three types of random flaps. The "best" drug was determined to be nitroglycerin. Its efficacy was verified in a primate model.

  View details for Web of Science ID A1989AL05100004

  View details for PubMedID 2505660

• PATHO-PHYSIOLOGY OF CLEFT-LIP MUSCLE PLASTIC AND RECONSTRUCTIVE SURGERY Schendel, S. A., Pearl, R. M., DeArmond, S. J. 1989; 83 (5): 777-784

  Abstract

  Although attention has been focused for decades on the correction of cleft lip deformities, our knowledge about the etiology of such deformities has remained presumptive. Sixty-six muscle biopsy specimens from cleft lip infants were obtained at the time of primary closure. Histochemical stains, histographic analysis, and electron microscopy were performed. A nonneurogenic muscle atrophy was seen that varied in severity, with muscle fibers near the cleft being the most atrophic and disorganized. Muscle fibers stained with the modified Gomori trichrome technique also demonstrated "ragged red" fibers typical of a mitochondrial myopathy. Electron microscopy confirmed large accumulations of mitochondria distorting the fibrils. These mitochondria also were increased in size and densely packed with cristae. This study thus demonstrates that the muscles in cleft lip deformities are not normal. Instead, they reflect either myopathy in the facial mesenchymal mitochondrion or at least a delay in maturation. We hypothesize that some of the morphologic deformities associated with cleft lip may cause a failure of mesenchymal reinforcement of the facial processes at a critical time in development.

  View details for Web of Science ID A1989U402700002

  View details for PubMedID 2469093

• INSTANTANEOUS AND CONTINUOUS CARDIAC-OUTPUT OBTAINED WITH A DOPPLER PULMONARY-ARTERY CATHETER JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Segal, J., Pearl, R. G., Ford, A. J., Stern, R. A., GEHLBACH, S. M. 1989; 13 (6): 1382-1392

  Abstract

  A newly developed, flow-directed, Doppler pulmonary artery catheter, capable of measuring instantaneous and continuous cardiac output, was evaluated in both an in vitro pump model and an animal model. Quantitative flow was calculated with use of the instantaneous, space-average velocity (obtained from the velocity profile) and the instantaneous area (obtained from the vessel diameter) and compared with electromagnetic flow. Additionally, simultaneous thermodilution flow measurements were obtained. Doppler catheter-determined flow was highly predictive of electromagnetic flow in both continuous and pulsatile pump models (r2 = 0.98, slope or m = 1.04, SEE = 0.44; and r2 = 0.97, m = 1.04 and SEE = 0.33, respectively). Thermodilution was less predictive and appeared to underestimate electromagnetic flow in both the continuous and the pulsatile model (r2 = 0.99, m = 0.91, SEE = 0.20 and r2 = 0.95, m = 0.84 and SEE = 0.34, respectively). In the animal model, Doppler catheter-determined cardiac output appeared to modestly underestimate electromagnetic flow (r2 = 0.80, m = 0.87, SEE = 0.61). However, Doppler determinations of flow remained more accurate than did simultaneous thermodilution measurements (r2 = 0.73, m = 0.79, SEE = 0.72). Accurate, continuous and instantaneous cardiac output measurements appear possible with use of a flow-directed, Doppler pulmonary artery catheter. This catheter system also provides instantaneous diameter measurements and mapping of instantaneous velocity profiles within the main pulmonary artery and may lead to more accurate Doppler-derived assessment of cardiac output in humans.

  View details for Web of Science ID A1989U337400023

  View details for PubMedID 2703619

• HYPERGLYCEMIA DECREASES ACUTE NEURONAL ISCHEMIC CHANGES AFTER MIDDLE CEREBRAL-ARTERY OCCLUSION IN CATS STROKE ZASSLOW, M. A., Pearl, R. G., Shuer, L. M., Steinberg, G. K., LIEBERSON, R. E., Larson, C. P. 1989; 20 (4): 519-523

  Abstract

  Hyperglycemia has been reported to worsen the tolerance of the brain to ischemia, and it has therefore been recommended that patients undergoing neurosurgical procedures not receive glucose-containing solutions. However, whereas most animal studies have used global ischemia models, most neurosurgical procedures are associated with risks of focal rather than global ischemia. We therefore studied the effects of glucose administration in an animal model of focal cerebral ischemia. We anesthetized 20 cats with halothane (0.85% end tidal in oxygen), and a focal cerebral ischemic lesion was produced by clip ligation of the left middle cerebral artery using a transorbital approach. Hyperglycemia (10 cats, mean +/- SEM plasma glucose concentration 561 +/- 36 mg/dl) was established before ligation by infusion of 50% glucose in 0.45% saline; the control group (10 cats, mean +/- SEM plasma glucose concentration 209 +/- 28 mg/dl) received 0.45% saline only. Total fluid administered, mean arterial blood pressure, body temperature, and arterial blood gas values did not differ between the two groups 0, 2, and 6 hours after ligation. The cats were killed 6 hours after ligation, and the area of severe ischemic neuronal damage was determined by microscopic examination of a coronal section at the level of the optic chiasm. The mean +/- SEM area of left cortical severe ischemic neuronal damage was 12 +/- 2% of the left cortex in the hyperglycemic group compared with 28 +/- 5% in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1989U149900014

  View details for PubMedID 2929029

• THE LONGITUDINAL DISTRIBUTION OF PULMONARY VASCULAR-RESISTANCE DURING UNILATERAL HYPOXIA ANESTHESIOLOGY Siegel, L. C., Pearl, R. G., Shafer, S. L., REAM, A. K., Prielipp, R. C. 1989; 70 (3): 527-532

  Abstract

  Pulmonary capillary hydrostatic pressure and the longitudinal distribution of pulmonary vascular resistance (arterial and venous components) can be determined by analysis of pressure decay curves following pulmonary artery occlusion. To validate this technique in intact animals, pulmonary artery occlusion pressure decay curves were obtained from both lungs in six anesthetized sheep during control conditions (100% O2) and during unilateral hypoxic ventilation (100% O2 versus 100% N2). Analysis of pulmonary artery occlusion pressure curves indicated the following: 1) in the hypoxic lung, unilateral hypoxia increased the precapillary portion of pulmonary vascular resistance from 72% of the total resistance to 89% of the total resistance in that lung; 2) in the nonhypoxic lung, unilateral hypoxia did not significantly affect the distribution of pulmonary vascular resistance; and 3) unilateral hypoxia produced no significant change in pulmonary capillary pressure in the hypoxic lung compared with control; however, pulmonary capillary pressure was significantly greater in the nonhypoxic lung. These results are consistent with other evidence that hypoxic pulmonary vasoconstriction acts locally and primarily affects resistance at the arteriolar level. Pulmonary artery occlusion pressure decay curve analysis appears to be a valid technique for the measurement of pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance in intact anesthetized animals. These measurements pertain only to the vasculature distal to the site of pulmonary artery occlusion with the catheter, and, thus, caution must be used when applying this technique in a setting of nonhomogenous lung injury.

  View details for Web of Science ID A1989T501200025

  View details for PubMedID 2923299

• AN APPROACH TO MANDIBULAR RECONSTRUCTION ANNALS OF PLASTIC SURGERY Pearl, R. M., Lepore, V., Hentz, V. R., SARIG, A. 1988; 21 (5): 401-417

  Abstract

  Mandibular reconstruction requires the restitution of both form and function. Proper preoperative planning, vascularized bone grafts, rigid fixation, flexibility of donor site choices, and restoration of labial, buccal, and lingual sulci lead to optimal reconstruction. We have used this approach in 38 patients; bony survival resulted in 37 and primary union in 35. A main limiting factor exists with individuals who have lost extensive amounts of soft tissue and muscle at the time of tumor resection or trauma. Only by attention to details in the preoperative, intraoperative, and postoperative phases can the best functional and aesthetic results be achieved.

  View details for Web of Science ID A1988Q973500002

  View details for PubMedID 3069032

• HEMODYNAMIC PROFILES OF PROSTAGLANDIN-E1, ISOPROTERENOL, PROSTACYCLIN, AND NIFEDIPINE IN VASOCONSTRICTOR PULMONARY-HYPERTENSION IN SHEEP ANESTHESIA AND ANALGESIA Prielipp, R. C., Rosenthal, M. H., Pearl, R. G. 1988; 67 (8): 722-729

  Abstract

  Patients with pulmonary hypertension challenge the anesthesiologist with complex alterations of hemodynamic function. To study the effects of multiple therapeutic interventions, a stable model of pulmonary hypertension in sheep was developed using continuous infusion of the vasoconstrictor U46619, a thromboxane A2-mimetic. The pulmonary and systemic effects of four pulmonary vasodilators (prostaglandin E1, isoproterenol, prostacyclin, and nifedipine) were compared at doses producing equivalent reduction in systemic blood pressure. Although all four drugs decreased pulmonary artery pressure and resistance, distinct differences in drug hemodynamic profiles were found. Prostaglandin E1 and isoproterenol demonstrated the greatest pulmonary specificity, increased cardiac output significantly, and decreased pulmonary vascular resistance. Prostaglandin E1 produced the largest decrease in pulmonary artery pressure (from 31 +/- 1 to 22 +/- 2 mm Hg). Isoproterenol markedly increased heart rate (from 119 +/- 6 to 182 +/- 10 beats/min) and resulted in significant dysrhythmias that necessitated limiting infusion of this drug; isoproterenol did not affect stroke volume. Prostacyclin demonstrated intermediate pulmonary specificity and produced the largest increase in cardiac output (from 1.7 +/- 0.2 to 3.1 +/- 0.3 L/min). Nifedipine exhibited the least pulmonary specificity and was the least effective agent in decreasing pulmonary artery pressure. In this model different pulmonary vasodilators exerted different hemodynamic effects, suggesting that appropriate drug selection for treatment of pulmonary hypertension should depend on baseline heart rate and rhythm, pulmonary artery pressure, systemic artery pressure, arterial oxygenation, and cardiac output.

  View details for Web of Science ID A1988P427600002

  View details for PubMedID 3293483

• EFFECT OF HEPARINIZATION OF CATHETERS ON PULMONARY-ARTERY OXIMETRY JOURNAL OF CLINICAL MONITORING STRITTER, G. M., Pearl, R. G., Mihm, F. G. 1988; 4 (3): 204-209

  Abstract

  A clinical study was performed in two phases to determine whether pulmonary artery oximeter catheters that were impregnated or bonded with heparin would affect the accuracy of measurements of in vivo mixed venous oxygen saturation (Sv-O2). In phase 1, 40 patients were catheterized with either a heparin-impregnated or a plain pulmonary artery catheter. Blood was sampled at random times to correlate in vivo with in vitro Sv-O2 measurements. In phase 2, 16 patients who were not receiving systemic heparin therapy or aspirin and who had no coagulopathies were catheterized with either a heparin-bonded or a plain pulmonary artery catheter in a blinded order. In phase 1, a total of 364 blood samples were obtained from 40 patients. Linear regression analysis of the pooled data demonstrated y = 0.98x - 0.01, r = 0.93, P less than 0.001, and n = 141 with heparin-impregnated catheters; and y = 0.87x + 8.0, r = 0.81, P less than 0.001, and n = 223 with plain catheters. The mean difference (in vivo minus in vitro) revealed a similar error (-1.3 +/- 0.4 versus -1.4 +/- 0.4, respectively, mean +/- SE). The 95% confidence limits of an individual value (+/- 8.1 versus +/- 12.3) suggested slightly greater accuracy with heparin-impregnated catheters. In phase 2, a total of 134 blood samples were obtained from 16 patients. Linear regression analysis showed nearly equal performance with heparin-bonded and plain catheters (r = 0.97 versus r = 0.98, respectively) with similar slopes (1.0 versus 1.1, respectively) but different intercepts (-0.6 versus -8.4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1988P442000007

  View details for PubMedID 3210068

• PEEP DOES NOT AFFECT LEFT ATRIAL-RIGHT ATRIAL PRESSURE DIFFERENCE IN NEUROSURGICAL PATIENTS ANESTHESIOLOGY ZASSLOW, M. A., Pearl, R. G., Larson, C. P., Silverberg, G., SHUER, L. F. 1988; 68 (5): 760-763

  Abstract

  Positive end-expiratory pressure (PEEP) has been used to prevent and treat venous air embolism in patients in the seated position undergoing neurosurgical operations. However, the safety of PEEP has recently been questioned, because of concern that PEEP might increase right atrial pressure (RAP) more than left atrial pressure, thereby predisposing patients with a probe-patent foramen ovale to paradoxical air embolism. In a prior study in dogs, the authors found that to up 10 cm H2O PEEP did not affect the interatrial pressure difference. In the present study, the authors examined the effects of 0, 5, and 10 cm H2O PEEP in 12 anesthetized neurosurgical patients positioned both supine and seated prior to operation. Measurements were made of systemic arterial pressure, RAP, mean pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), and cardiac output. PAWP was higher (average 2 mmHg) than RAP in all patients. PEEP increased RAP and PAWP in patients, both seated and supine (mean 3 mmHg at 10 cm H2O), but did not affect the PAWP-RAP difference. In an additional eight patients in the seated position, the authors examined the effects of 0, 10, and 20 cm H2O PEEP during operation. PEEP again increased PAWP and RAP, but did not significantly affect the PAWP-RAP difference. The PAWP-RAP difference became negative (-1 mmHg) in one patient with 20 cm H2O PEEP. The authors conclude that levels of PEEP up to 10 cm H2O do not alter the interatrial pressure difference in seated neurosurgical patients, and, therefore, would not predispose these patients to paradoxical air embolism.

  View details for Web of Science ID A1988N243200014

  View details for PubMedID 3285733

• VASODILATOR THERAPY IN VASOCONSTRICTOR-INDUCED PULMONARY-HYPERTENSION IN SHEEP ANESTHESIOLOGY Prielipp, R. C., Rosenthal, M. H., Pearl, R. G. 1988; 68 (4): 552-558

  Abstract

  A stable preparation of pulmonary hypertension in sheep was developed using a continuous infusion of the vasoconstrictor U46619, a stable endoperoxide thromboxane A2-mimetic. Using this model, the pulmonary and systemic effects of nitroglycerin, sodium nitroprusside, hydralazine, and prostaglandin E1 were compared at doses producing equivalent reductions in systemic blood pressure. Although all four drugs decreased pulmonary artery pressure and resistance, different drug hemodynamic profiles were found. Prostaglandin E1 demonstrated the greatest pulmonary specificity and resulted in the largest decrease in pulmonary artery pressure (from 33 +/- 1 to 23 +/- 1 mmHg). Nitroglycerin and sodium nitroprusside demonstrated intermediate pulmonary specificity and did not affect cardiac output. Hydralazine demonstrated the least pulmonary specificity and resulted in a large decrease in systemic vascular resistance, with only a moderate decrease in pulmonary artery pressure and resistance. Rational selection of pulmonary vasodilators for clinical application will vary depending on baseline heart rate and rhythm, pulmonary artery pressure, systemic artery pressure, and cardiac output.

  View details for Web of Science ID A1988M799800013

  View details for PubMedID 3128144

• EFFECTS OF SPINAL-ANESTHESIA ON RESPONSE TO MAIN PULMONARY ARTERIAL DISTENSION JOURNAL OF APPLIED PHYSIOLOGY Pearl, R. G., McLean, R. F., Rosenthal, M. H. 1988; 64 (2): 742-747

  Abstract

  Nonocclusive main pulmonary arterial distension produces peripheral pulmonary hypertension. The mechanism of this response is unknown. The effects of total spinal anesthesia on the response were studied in halothane-anesthetized dogs. Before total spinal anesthesia, main pulmonary arterial balloon inflation increased pulmonary arterial pressure and resistance without affecting systemic hemodynamic variables. Both right and left pulmonary arterial pressures were monitored to exclude unilateral obstruction with main pulmonary arterial balloon inflation. Total spinal anesthesia decreased cardiac output and systemic arterial pressures. After total spinal anesthesia, main pulmonary arterial distension still increased pulmonary arterial pressure and resistance. Right atrial pacing, discontinuation of halothane anesthesia, and norepinephrine infusion during total spinal anesthesia partially reversed the hemodynamic changes caused by total spinal anesthesia. The percent increase in pulmonary vascular resistance due to main pulmonary arterial distension was similar before total spinal anesthesia and during all experimental conditions during total spinal anesthesia. The pulmonary hypertensive response is therefore not dependent on central synaptic connections.

  View details for Web of Science ID A1988M317200033

  View details for PubMedID 3372430

• MEASUREMENT OF THE LONGITUDINAL DISTRIBUTION OF PULMONARY VASCULAR-RESISTANCE FROM PULMONARY-ARTERY OCCLUSION PRESSURE PROFILES ANESTHESIOLOGY Siegel, L. C., Pearl, R. G. 1988; 68 (2): 305-307

  View details for Web of Science ID A1988L961800036

  View details for PubMedID 3341595

• PULMONARY EFFECTS OF CRYSTALLOID AND COLLOID RESUSCITATION FROM HEMORRHAGIC-SHOCK IN THE PRESENCE OF OLEIC ACID-INDUCED PULMONARY CAPILLARY INJURY IN THE DOG ANESTHESIOLOGY Pearl, R. G., Halperin, B. D., Mihm, F. G., Rosenthal, M. H. 1988; 68 (1): 12-20

  Abstract

  The effects of resuscitation with crystalloid and colloid solutions in the presence of increased pulmonary capillary permeability were studied. Twenty-four hours after oleic acid administration, dogs were anesthetized and bled to produce hemorrhagic shock. One hour later, resuscitation was performed with saline, 5% albumin, or 6% hydroxyethyl starch solution to restore and then maintain cardiac output at pre-oleic acid values for 6 h. Dogs were recovered and, 24 h later, were reanesthetized for final measurements. Oleic acid administration resulted in increases in pulmonary artery pressure, pulmonary vascular resistance, and extravascular lung water (EVLW). Resuscitation from hemorrhagic shock restored pulmonary hemodynamics to pre-hemorrhage levels and did not affect EVLW, PaO2, shunt fraction, dead-space-to-tidal-volume ratio, or pulmonary compliance. There were no differences in these parameters related to the choice of resuscitation fluid. Saline resuscitation markedly reduced plasma oncotic pressure and the plasma oncotic-pulmonary artery occlusion pressure gradient. Values for these two variables were markedly lower with saline than with colloid resuscitation. The authors conclude that the pulmonary effects of crystalloid and colloid solutions are similar in the presence of moderate increases in pulmonary capillary permeability.

  View details for Web of Science ID A1988L597700004

  View details for PubMedID 3337363

• THE RADIAL FOREARM FLAP - A VERSATILE SOURCE OF COMPOSITE TISSUE ANNALS OF PLASTIC SURGERY Hentz, V. R., Pearl, R. M., Grossman, J. A., Wood, M. B., Cooney, W. P. 1987; 19 (6): 485-498

  Abstract

  The radiovolar area of the forearm constitutes a versatile source of composite tissues for pedicle flap reconstruction of the hand and free-flap reconstruction for many areas of the body. The skin is thin and relatively hairless, and the vascular pedicle is long and of large caliber. The flap can be harvested to contain vascularized tendons and bone. The skin can be reliably reinnervated. The principal disadvantage, that this is a conspicuous donor site, has not been a source of concern for our patients. Nineteen of the 20 (95%) free flaps survived completely.

  View details for Web of Science ID A1987L530700001

  View details for PubMedID 3439761

• SURGICAL-MANAGEMENT OF VOLUMETRIC CHANGES IN THE BONY ORBIT ANNALS OF PLASTIC SURGERY Pearl, R. M. 1987; 19 (4): 349-358

  Abstract

  This article demonstrates that the periorbital fat, instead of being continuous and freely flowing, is encased within 3 compartments: 1 anterior to the extraocular muscles, 1 external to the extraocular muscles, and 1 deep to the extraocular muscles. In addition, the study establishes that fat loss anterior to the axis of the globe does not affect the anteroposterior location of the eye itself. Only fractures located posterior to the axis produce enophthalmos, and only operative procedures that create bony enlargement and fatty displacement behind this axis correct exophthalmos. Furthermore, only adding volume behind the axis of the globe can correct enophthamos. Finally, if there is sufficient space between the top of the globe and the bony roof, volume additions at the axis of the globe can correct vertical dystopia without producing exophthalmos.

  View details for Web of Science ID A1987K522000011

  View details for PubMedID 3688781

• Application of free tissue transfers to the foot. Journal of reconstructive microsurgery Hentz, V. R., Pearl, R. M. 1987; 3 (4): 309-320

  Abstract

  During the past five years we have used three sources of free tissue transfers in 26 patients to reconstruct defects of the ankle and dorsum, hind, mid- and forefoot, defects poorly or unamenable to traditional reconstructive methods. These included free muscle transfers covered with a skin graft, temporoparietal fascia also covered with a graft, and radial forearm skin or fascia. In addition, six complex defects were reconstructed with composite tissue free transfers, usually tendinocutaneous flaps. There was one partial flap loss. All were successful in both healing the defect and in providing functional restoration, except in the forefoot. From an analysis of these cases, we have developed indications for various transfers based on the functional needs of the area involved and donor site requirements.

  View details for PubMedID 2888887

• CARE OF THE ADULT PATIENT DURING TRANSPORT INTERNATIONAL ANESTHESIOLOGY CLINICS Pearl, R. G., Mihm, F. G., Rosenthal, M. H. 1987; 25 (2): 43-75

  Abstract

  Interhospital transport of the critically ill patient involves maintaining the same quality of care that was present before transport. This requires planning for equipment, space, and personnel needs during transport, and instituting adequate pathophysiologically based treatment and stabilization prior to transport. Under such conditions, transport can be safely accomplished and have a positive impact on patient care.

  View details for Web of Science ID A1987H793900004

  View details for PubMedID 3301685

• Hematologic effects of cardiac and noncardiac surgery. Journal of cardiothoracic anesthesia Pearl, R. G., Sladen, R. N., Rosenthal, M. H. 1987; 1 (3): 205-209

  Abstract

  The intraoperative and postoperative changes in number and type of WBCs in patients undergoing cardiac surgery were studied. These changes were then compared with those that occurred in patients undergoing four noncardiac surgical procedures (abdominal vascular reconstruction, thoracotomy, cholecystectomy, and carotid thromboendarterectomy). Both cardiac surgery and abdominal vascular surgery resulted in a marked increase in bands and decrease in lymphocytes. Thoracotomy and cholecystectomy resulted in similar but smaller changes. Carotid thromboendarterectomy did not produce hematologic changes. We conclude that the hematologic changes that occur with cardiac surgery are primarily a result of the stress and trauma of major surgery rather than a result of cardiopulmonary bypass itself.

  View details for PubMedID 2979095

• Pulmonary and systemic hemodynamic effects of central venous and left atrial sympathomimetic drug administration in the dog. Journal of cardiothoracic anesthesia Pearl, R. G., Maze, M., Rosenthal, M. H. 1987; 1 (1): 29-35

  Abstract

  Systemic vasopressor or inotropic therapy may exacerbate existing pulmonary hypertension; the optimal agent and route of administration in this situation are unknown. The systemic and pulmonary hemodynamic effects of four sympathomimetic agents (dopamine, epinephrine, norepinephrine, and phenylephrine) during central venous and left atrial administration were investigated in the anesthetized dog. All four drugs increased both systemic and pulmonary artery pressures. Dopamine and epinephrine increased cardiac output and reduced systemic vascular resistance. Phenylephrine decreased cardiac output and increased systemic vascular resistance and left atrial pressure. Norepinephrine did not significantly affect cardiac output, systemic vascular resistance, or left atrial pressure. None of the four drugs affected pulmonary vascular resistance. The ratio of systemic to pulmonary vascular resistance decreased with epinephrine and increased with phenylephrine. There were no hemodynamic differences related to the route of infusion for any of the four drugs. However, pulmonary arterial concentrations of the three drugs measured (dopamine, epinephrine, and norepinephrine) were markedly lower during left atrial compared to central venous drug administration; systemic drug concentrations were similar or increased during left atrial compared to central venous drug administration. It is concluded that the relative effects on the systemic and pulmonary circulations differ for the four drugs; rational choice of a vasopressor will depend upon the hemodynamic situation and the desired effect. Left atrial catecholamine administration is effective in decreasing pulmonary arterial drug concentrations and may decrease adverse pulmonary effects in clinical practice.

  View details for PubMedID 2979068

• EFFECT OF INJECTATE VOLUME AND TEMPERATURE ON THERMODILUTION CARDIAC-OUTPUT DETERMINATION ANESTHESIOLOGY Pearl, R. G., Rosenthal, M. H., Nielson, L., ASHTON, J. P., Brown, B. W. 1986; 64 (6): 798-801

  Abstract

  Six combinations of injectate volume (10, 5, and 3 ml) and temperature (0 degree C and room temperature [RT]) are recommended by the manufacturers of thermodilution cardiac output catheters and computers. We prospectively studied the accuracy and variability associated with these six combinations in critically ill patients requiring intermittent mandatory ventilation. The six methods were similar in their average estimation of cardiac output but differed markedly in their reproducibility. The 10 ml 0 degree C and 10 ml RT combinations produced the least variability. The 5 ml 0 degree C and 5 ml RT combinations produced more variability. Variability was much greater with the remaining two combinations. The 3 ml RT combination resulted in an average range of 1.71 1/min within each set of three repeat measurements and an average absolute difference of 1.51 1/min from the values obtained with 10 ml 0 degree C (each the mean of three injections). We recommend the use of 10 ml 0 degree C or 10 ml RT for cardiac output determinations in critically ill patients. If it is important to minimize volume administration, the use of 5 ml injectate is acceptable for an estimation of cardiac output. The use of 3 ml injectate volumes is rarely, if ever, justified because the small reduction in volume administration results in a large increase in variability.

  View details for Web of Science ID A1986C527700021

  View details for PubMedID 3717644

• HEMODYNAMIC-EFFECTS OF POSITIVE END-EXPIRATORY PRESSURE DURING CONTINUOUS VENOUS AIR-EMBOLISM IN THE DOG ANESTHESIOLOGY Pearl, R. G., Larson, C. P. 1986; 64 (6): 724-729

  Abstract

  Positive end-expiratory pressure (PEEP) may decrease venous air embolism (VAE) by increasing venous pressure at the incision level. Because PEEP and VAE can both increase pulmonary vascular resistance, it is possible that the application of PEEP during VAE may increase right atrial pressure (RAP) relative to left atrial pressure (LAP) and thereby reverse the normal interatrial pressure gradient, allowing paradoxical air embolism in patients with a probe-patent foramen ovale. We studied atrial pressures during 0, 4, and 8 mmHg PEEP before and during continuous VAE in both supine and upright tilted dogs. Both PEEP and VAE increased pulmonary artery pressure and resistance. Prior to VAE, PEEP increased both RAP and LAP but did not affect the interatrial pressure gradient. VAE alone did not affect RAP, LAP, or the interatrial pressure gradient. Application of PEEP during VAE had similar effects as at baseline, namely an increase in RAP and LAP with no change in the interatrial pressure gradient. Although RAP exceeded LAP more frequently in the upright than in the supine dogs, the effects of PEEP and VAE on atrial pressures were similar in both groups. Our finding that PEEP and VAE did not disproportionately increase RAP compared with LAP is consistent with other studies demonstrating preservation of right ventricular function in situations of increased right ventricular afterload.

  View details for Web of Science ID A1986C527700008

  View details for PubMedID 3521392

• NITROGLYCERIN-RESPONSIVE PULMONARY-HYPERTENSION IN IDIOPATHIC PULMONARY HEMOSIDEROSIS AMERICAN REVIEW OF RESPIRATORY DISEASE Frankel, L. R., Smith, D. W., Pearl, R. G., LEWISTON, N. J. 1986; 133 (1): 170-172

  Abstract

  Idiopathic pulmonary hemosiderosis (IPH) is an uncommon disease found predominantly in pediatric patients. It can produce severe chronic pulmonary injury that results in chronic hypoxemia, pulmonary insufficiency, and progressive pulmonary fibrosis, leading to irreversible pulmonary hypertension and death. We studied the pulmonary hemodynamics in an 9-yr-old boy with IPH to determine if pulmonary hypertension contributed to exacerbations of this disease. Our results showed that this patient demonstrated pulmonary hypertension during acute exacerbations. Initially, the elevated pulmonary artery pressure responded both to oxygen and to a pulmonary vasodilator in the form of nitroglycerin. However, this improvement was not sustained. We conclude that pulmonary hypertension is probably a result of chronic hypoxemia experienced by patients with pulmonary hemosiderosis. Further investigation is warranted to assess whether or not intervention aimed at reducing pulmonary artery pressure in IPH improves outcome.

  View details for Web of Science ID A1986AXX6000031

  View details for PubMedID 3079975

• METABOLIC ALKALOSIS DUE TO PLASMAPHERESIS AMERICAN JOURNAL OF MEDICINE Pearl, R. G., Rosenthal, M. H. 1985; 79 (3): 391-393

  Abstract

  Progressive metabolic alkalosis developed in two patients undergoing daily plasmapheresis for diffuse intrapulmonary hemorrhage associated with glomerulonephritis (Goodpasture's-like syndrome). The metabolic alkalosis promptly resolved when the plasmapheresis procedure was altered so that 3 percent albumin and cryoprecipitate rather than fresh frozen plasma were used as replacement for the removed patient plasma. The development of metabolic alkalosis during plasmapheresis can be explained by the large sodium citrate load given during the procedure. Severe metabolic alkalosis may develop in patients with decreased renal function when they are treated with plasmapheresis. The metabolic alkalosis can be prevented by appropriate modifications in the plasmapheresis protocol.

  View details for Web of Science ID A1985ARB2300022

  View details for PubMedID 3929603

• LUNG WATER FOLLOWING RESUSCITATION WITH COLLOID AND CRYSTALLOID SOLUTIONS Halperin, B. D., Pearl, R. G., Rosenthal, M. H., ASHTON, J. P., Mihm, F. G., Feeley, T. W. WILLIAMS & WILKINS. 1984: 226–26

  View details for Web of Science ID A1984SB26300074

• PULMONARY-HYPERTENSION IN IDIOPATHIC PULMONARY HEMOSIDEROSIS - FAVORABLE RESPONSE TO NITROGLYCERIN THERAPY Frankel, L., Pearl, R., BLESSINGMOORE, J., Smith, D., LEWISTON, N., Rosenthal, M. SLACK INC. 1984: A131–A131

  View details for Web of Science ID A1984RZ82200775

• AMINOPHYLLINE POTENTIATES SODIUM NITROPRUSSIDE-INDUCED HYPOTENSION IN THE DOG ANESTHESIOLOGY Pearl, R. G., Rosenthal, M. H., Murad, F., ASHTON, J. P. 1984; 61 (6): 712-715

  Abstract

  The biochemical mechanisms by which nitroso-vasodilators cause smooth muscle relaxation remain controversial. One theory states that the effects of nitroso-vasodilators are mediated by increased intracellular levels of cyclic GMP due to activation of guanylate cyclase. To test this hypothesis, the authors examined the effects of sodium nitroprusside (SNP) in anesthetized dogs with an without pretreatment with the phosphodiesterase inhibitor aminophylline. Aminophylline pretreatment resulted in a 2.8-fold potentiation of the hypotensive effects of a continuous infusion of SNP. Potentiation also was seen for the effects of SNP on stroke volume, heart rate, and plasma cyclic GMP levels. These results support the hypothesis that nitroso-vasodilators exert their effects via guanylate cyclase activation. The authors advise caution when vasodilator therapy with agents such as SNP, nitroglycerin, or hydralazine is instituted in patients receiving aminophylline and when aminophylline is either instituted or discontinued in patients on vasodilator therapy.

  View details for Web of Science ID A1984TV08000014

  View details for PubMedID 6095702

• NIACIN REDUCES OXYGEN-TOXICITY IN MOUSE ALVEOLAR MACROPHAGES PHARMACOLOGY Pearl, R. G., Raffin, T. A. 1983; 27 (4): 219-222

  Abstract

  Niacin at concentrations of 0.1-10 mM resulted in a dose-dependent reduction of oxygen toxicity in a mouse alveolar macrophage model. These concentrations of niacin did not affect alveolar macrophage function under normoxic conditions. Our results are consistent with observations from other groups that niacin reduces oxygen toxicity in bacteria and paraquat toxicity in bacteria and rats. The mechanism by which niacin reduces oxygen toxicity may involve the ability of niacin to function as an alternate substrate for NAD synthesis. Niacin may have clinical value in the prevention of oxygen toxicity.

  View details for Web of Science ID A1983RG21400006

  View details for PubMedID 6634933

• PULMONARY VASODILATOR EFFECTS OF NITROGLYCERIN AND SODIUM-NITROPRUSSIDE IN CANINE OLEIC ACID-INDUCED PULMONARY-HYPERTENSION ANESTHESIOLOGY Pearl, R. G., Rosenthal, M. H., ASHTON, J. P. 1983; 58 (6): 514-518

  Abstract

  The hemodynamic effects of nitroglycerin (TNG) and sodium nitroprusside (SNP) were studied in a canine model of pulmonary hypertension. Oleic acid administration resulted in pulmonary hypertension with a 133% increase in pulmonary vascular resistance (PVR), a 40% increase in mean pulmonary artery pressure (MPAP), and a 28% decrease in cardiac output (CO). In this model, subsequent TNG administration increased CO 40%, decreased PVR 43%, and decreased MPAP 12%; pulmonary hemodynamics during TNG administration were not significantly different from those prior to oleic acid administration. SNP produced systemic hypotension but did not alter either PVR or MPAP and increased CO only 14%. The efficacy of TNG in this model may relate to its ability to dilate preferentially the pulmonary vascular bed.

  View details for Web of Science ID A1983QU80800006

  View details for PubMedID 6407362

• ACUTE HEMODYNAMIC-EFFECTS OF NITROGLYCERIN IN PULMONARY-HYPERTENSION ANNALS OF INTERNAL MEDICINE Pearl, R. G., Rosenthal, M. H., Schroeder, J. S., ASHTON, J. P. 1983; 99 (1): 9-13

  Abstract

  Therapy of pulmonary hypertension is limited by the low potency and adverse effects of current pulmonary vasodilators. The hemodynamic effects of nitroglycerin in human pulmonary hypertension are not known. We administered nitroglycerin to nine patients with chronic pulmonary hypertension. Nitroglycerin increased cardiac index 40% (p less than 0.01), increased stroke volume 40% (p less than 0.01), decreased pulmonary vascular resistance 40% (p less than 0.01), and decreased mean pulmonary artery pressure 15% (p less than 0.01). Pulmonary vascular resistance decreased more than 25% in eight of the nine patients. In four patients the effects of intravenous nitroglycerin were reproduced by topical nitroglycerin preparations; cardiac index increased 50%, stroke volume increased 48%, pulmonary vascular resistance decreased 43%, and mean pulmonary artery pressure decreased 19%. Five of six patients treated with long-acting nitrates had substantial improvement of their symptoms. We conclude that therapy with nitroglycerin can be effective in patients with severe pulmonary hypertension.

  View details for Web of Science ID A1983QY17800002

  View details for PubMedID 6407380