The Cardiopulmonary Bypass, Hemolysis, and end organ function: an Integration of Political Science, Chemistry, and Zoology By Nathan V. Luce A capstone project submitted to the faculty of Weber State University in fulfillment of the requirements of the degree of Bachelor of Integrated Studies in the Department of Integrated Studies. Ogden, Utah (Date Approved) Approved by: Department Director Dr. Michael Cena Ph.D. Committee Members: Political Science Dr. Gary Johnson Ph.D. Clinical and Clinical Research: Chemistry and Zoology Dr. Peter C. Minneci M.D. Marie Hart Clayton MSN, RN TABLE OF CONTENTS PREFACE......................................................................................................................................... v INTRODUCTION............................................................................................................................... 1 HISTORY AND BASICS: CARDIAC SURGERY AND THE CPB.................................................... 3 Evolution of Cardiac Surgery............................................................................................ 3 Intraoperative........................................................................................................... 5 Effects of Cardiopulmonary Bypass................................................................................. 6 Mechanical............................................................................................................... 6 Physiological: Whole Body Inflammatory Response................................................ 6 THE INTEGRATION OF POLITICAL SCIENCE AND THE SCIENCES.......................................... 11 The Chemistry Component................................................................................................ 11 Discovery and Physical Properties of Nitric Oxide................................................... 11 The Zoology Component.................................................................................................... 13 NOs role in vascular flow and dynamics.................................................................. 14 Physiology: Kidney, heart, Lungs, Liver................................................................... 16 Policy and Politics.............................................................................................................. 17 Experimentation without Representation: a matter of consent and privacy……….. 18 HIPAA and other Civil Rights................................................................................... 23 Institutional Review Board....................................................................................... 26 Clinical Research: a balance between science and policy...................................... 27 METHODS OF ACADEMIC INQUIRY.............................................................................................. 30 Gaining Entry into a Research Lab................................................................................... 30 The Lab’s Research Objectives and Hypothesis............................................................. 31 My Lab Responsibilities..................................................................................................... 33 Data Management……………………………………………………………………….. 34 Blood and Urine Sample Collection......................................................................... 36 Devices used for Analysis........................................................................................ 37 Statistical Considerations.................................................................................................. 39 Protecting Participants’ Rights......................................................................................... 39 RESEARCH FINDINGS.................................................................................................................... 40 Physical and Biological Sciences..................................................................................... 40 Political Science.................................................................................................................. 49 DISCUSSION.................................................................................................................................... 50 Hemolysis and NO Consumption...................................................................................... 50 Administration and Socioeconomics………………………………………………………… 54 Obedience and Morality…………………………………………………………………. 54 The Socioeconomics of Clinical Research…........................................................... 56 CONCLUSION………………………………………………………………………………………………. 60 CAPSTONE PROJECT OUTCOMES............................................................................................... 62 What I Learned in My Experience...................................................................................... 62 My Future Plans for Academic Study and Employment................................................. 62 APPENDIX A-I.................................................................................................................................. i REFERENCES.................................................................................................................................. xii i LIST OF TABLES Table 1. Physical and Chemical Properties of Nitric Oxide............................................................................... 12 Table 2. Common biochemical, physiologic, and organ function tests............................................................. 17 Table 3. Informed Consent Checklist - Basic and Additional Elements............................................................ 22 Table 4. Parameters that play important roles in privacy in healthcare............................................................ 24 Table 5. Three primary hypothesize in the study of intravascular hemolysis and NO scavenging.................. 31 Table 6. Time period, title, protocol, location and responsibilities at HUP........................................................ 33 Table 7. Times with, title, protocol, location and responsibilities at CHOP....................................................... 34 Table 8. Case Report Form and post discharge timeline…………………………………………………………... 35 Table 9. Illustration of blood, urine, PHI time points and blood volumes…………………………………………. 36 Table 10. Digital reactive hyperemia challenge using Itamar endo-PAT 2000................................................... 37 Table 11. Methods of measuring OxyHb scavenging capabilities using Sievers Nitric Oxide Analyzer 280i….. 38 Table 12. UV spectrophotometer analysis.......................................................................................................... 38 Table 13. Intraoperative Details.......................................................................................................................... 41 Table 14. Hospital Course................................................................................................................................... 41 Appendix List of Tables A. Comprehensive record of surgeon, event, year, and outcomes in the development of the CPB ….............. i E. Educational demographics: a comparison of differences between blacks and whites.................................... vi ii LIST OF FIGURES Figure 1. CPB: circuitry, pump, oxygenator, heat exchange, cardioplegia.................................................... 4 Figure 2. Aortic and Venous cannulation during Mitral valve surgery............................................................ 4 Figure 3. Effects of extracorporeal circuit on plasma……………………………………………………………... 8 Figure 4. Exposure of blood to circuit and its effects on neutrophils and end-organ tissue damage............ 8 Figure 5. Activation of immune system and effects on neutrophils, endothelium and interstitial species…... 9 Figure 6. Endothelial response to injury via leukocyte adhesion molecules and procoagulant changes....... 10 Figure 7. Sequelae of intravascular hemolysis and NO scavenging by Hb molecules................................... 32 Figure 8. Pre-Admission Participant Characteristics………………………………………................................ 42 Figure 9. Procedure Type and Frequency....................................................................................................... 42 Figure 10. Morbidity and Mortality...................................................................................................................... 43 Figure 11. Overall OxyHb and NO consumption trends…………………………………………………………… 44 Figure 12. One hour OxyHb and NO consumption trends………………………………………………………… 44 Figure 13. Three hour OxyHb and NO consumption trends………………………………………………………. 45 Figure 14. Five hour OxyHb and NO consumption trends………………………………………………………… 45 Figure 15. Nine hour OxyHb and NO consumption trend…………………………………………………………. 46 Figure 16. Total patients and deaths per hour……………………………………………………………………… 47 Figure 17. One-hour mortality trend: NO cons and OxyHb……………………………………………………….. 47 Figure 18. Five-hour mortality trend: NO cons and OxyHb……………………………………………………….. 48 Figure 19. Off pump mortality trend: NO cons and OxyHb……………………………………………………….. 48 Appendix List of Figures B. University of Pennsylvania Research Subject Informed Consent Form…................................................... ii C. University of Pennsylvania-Office of Regulatory Affairs IRB Review…......................................................