Bio

Clinical Focus


  • Anesthesia

Academic Appointments


Administrative Appointments


  • Chair, Stanford University School of Medicine - Anesthesia Department (1999 - Present)

Professional Education


  • Residency:Stanford University School of Medicine (1985) CA
  • Fellowship:Stanford University School of Medicine (1981) CA
  • Residency:Stanford University School of Medicine (1980) CA
  • Internship:Stanford University School of Medicine (1978) CA
  • Board Certification: Anesthesia, American Board of Anesthesiology (1986)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1980)
  • Board Certification: Critical Care Medicine, American Board of Anesthesiology (1986)
  • Medical Education:University of Chicago Hospitals (1977) IL
  • MD, University of Chicago, Medicine (1977)
  • PhD, University of Chicago, Pharmacology and Physiology (1975)
  • BS, Yale University, Psychology (1971)

Research & Scholarship

Current Research and Scholarly Interests


Mechanims (molecular and cellular) of pulmonary hypertension, treatment of pulmonary hypertension, treatment of respiratory failure, treatment of septic shock, hemodynamic monitoring

Clinical Trials


  • Protocolized Care for Early Septic Shock Not Recruiting

    The ProCESS study is large, 5-year, multicenter study of alternative resuscitation strategies for septic shock. The study hypothesizes that there are "golden hours" in the initial management of septic shock where prompt, rigorous, standardized care can improve clinical outcomes.

    Stanford is currently not accepting patients for this trial. For more information, please contact Valerie Ojha, (650) 498 - 6210.

    View full details

  • Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study (The APEX Study) Recruiting

    The purpose of this study is to evaluate whether extended prophylaxis with oral betrixaban can prevent blood clots in the leg and lung that sometime occur in patients hospitalized for an acute medical illness and to compare these results with standard of care enoxaparin. The safety of betrixaban will also be studied.

    View full details

  • A Study Comparing Ceftazidime-Avibactam+Metronidazole Versus Meropenem in Adults With Complicated Intra-abdominal Infections Recruiting

    The purpose of this study is to evaluate the effects of Ceftazidime Avibactam plus Metronidazole compared to Meropenem for treating hospitalized patients with complicated intra-abdominal infections.

    View full details

  • Safety and Efficacy of Polymyxin B Hemoperfusion (PMX) for Septic Shock Recruiting

    To compare the safety and efficacy of the PMX cartridge based on mortality at 28-days in subjects with septic shock who have high levels of endotoxin and are treated with standard medical care plus use of the PMX cartridge, versus subjects who receive standard medical care alone.

    View full details

  • Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection Recruiting

    The aim of this study is to evaluate the efficacy of the candidate Clostridium difficile (C. difficile) vaccine to prevent primary symptomatic C. difficile infection (CDI) in subjects a risk for CDI where there is a substantial unmet medical need. Primary objective: - To assess the efficacy of the C. difficile vaccine in preventing the onset of symptomatic primary CDI confirmed by polymerase chain reaction (PCR) in adult subjects aged ≥ 50 years who are at risk for CDI and have received at least 1 injection. Secondary Objectives: Efficacy: - To assess prevention of symptomatic PCR-confirmed primary CDI cases after 3 injections administered at 0, 7, and 30 days - To assess prevention of symptomatic PCR-confirmed primary CDI cases after completion of at least 2 injections. Immunogenicity: - To describe the immunogenicity to toxin A and toxin B in the subset of subjects at specific time points. Safety: - To describe the safety profile of all subjects who receive at least 1 injection.

    View full details

Teaching

2013-14 Courses


Publications

Journal Articles


  • 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

  • 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 Web of Science ID 000309020900031

    View details for PubMedID 22943790

  • 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 Web of Science ID 000286576000023

    View details for PubMedID 21081766

  • 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

  • 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
  • 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

  • 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 Web of Science ID 000222088800009

    View details for PubMedID 15082832

  • 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

  • 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 Web of Science ID 000185624500032

    View details for PubMedID 12963647

  • 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 Web of Science ID 000182411900033

    View details for PubMedID 12682495

  • 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 Web of Science ID 000179116500019

    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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

Conference Proceedings


  • Nitroglycerin does not alter pulmonary vascular permeability in isolated rabbit lungs Thompson, J. S., Kavanagh, B. P., Pearl, R. G. LIPPINCOTT WILLIAMS & WILKINS. 1997: 359-362

    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 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

  • Inhibition of endogenous nitric oxide synthase potentiates nitrovasodilators in experimental pulmonary hypertension Kavanagh, B. P., Thompson, J. S., Pearl, R. G. LIPPINCOTT WILLIAMS & WILKINS. 1996: 860-866

    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

  • A THROMBOXANE ANALOG INCREASES PULMONARY CAPILLARY-PRESSURE BUT NOT PERMEABILITY IN THE PERFUSED RABBIT LUNG WAKERLIN, G. E., BENSON, G. V., Pearl, R. G. LIPPINCOTT WILLIAMS & WILKINS. 1991: 475-480

    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

Stanford Medicine Resources: