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Mechanisms of Functional Tricuspid Valve Regurgitation in Ischemic Cardiomyopathy

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Mechanisms of Functional Tricuspid Valve Regurgitation in Ischemic Cardiomyopathy University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 2005 Mechanisms of functional tricuspid valve regurgitation in ischemic cardiomyopathy Thomas M. Joudinaud The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Joudinaud, Thomas M., "Mechanisms of functional tricuspid valve regurgitation in ischemic cardiomyopathy" (2005). Graduate Student Theses, Dissertations, & Professional Papers. 9567. https://scholarworks.umt.edu/etd/9567 This Dissertation is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact [email protected]. NOTE TO USERS This reproduction is the best copy available. UMI Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Maureen and Mike MANSFIELD LIBRARY The University of Montana Permission is granted by the author to reproduce this material in its entirety, provided that this material is used for scholarly purposes and is properly cited in published works and reports. '*Please check "Yes" or "No" and provide signature Yes, I grant permission K No, I do not grant permission _________ Author's Signature: -------- Date :_______ 03 wA oS Any copying for commercial purposes or financial gain may be undertaken only with the author's explicit consent. 8/98 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Mechanisms of Functional Tricuspid Valve Regurgitation in Ischemic Cardiomyopathy By Thomas M Joudinaud M.D. University of Paris-Versailles-Saint Quentin en Yvelines, France, 2003 Presented in partial fulfillment of the requirements For the degree of Doctor of Philosophy The University of Montana July 2005 Approved by: Dean, Graduate School g -3 Q - 05" Date Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: 3184231 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. UMI UMI Microform 3184231 Copyright 2005 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Joudinaud, Thomas M., Ph.D., July 2005 IIP Mechanisms of Functional Tricuspid Valve Regurgitatiçtn in Ischemic Cardiomyopathy. Chairperson: Carlos M.G. Duran, M.D., Ph.D. In heart failure, the presence of functional mitral r%#gitation secondary to a myocardial infarction (MI) is known to double mortality. While the mechanism of functional mitral regurgitation has been extensively studied, the mechanism of a concomitant functional tricuspid regurgitation has been neglected. We hypothesizedthat MI alters not only the geometry of the left ventricle but also of the right ventricle leading to both ischemic mitral and tricuspid regurgitation (IMR & ITR). We also hypothesized that these geometric alterations modulate mechanical stresses resulting in molecular changes. To answer these hypotheses, the following Aims were designed: 1) complete an anatomy study of the normal tricuspid valve following the established principles applied to the mitral valve; 2) perform an in vivo sonometric study of the functional anatomy of the atrioventricular valves in order to clarify their relationships; 3) compare in sheep the data obtained with transthoracic echocardiography (TTE) with those acquired with sonomicrometry. Evaluation of the reliability of the echo geometric data is essential given its value because of its non-invasiveness. 4) develop a reproducible animal model of IMR and ITR and analyze the resulting geometrical changes 5) search for variations in eNOS and nNOS expression at increasing distance from the MI as an indicator of cardiomyocyte stretch. Results 1) An original terminology of the tricuspid valve useful to surgeons and cardiologists was developed; 2) we showed how the mitral and tricuspid valves are linked by the septum; 3) TTE in sheep provides precise information needed for the non invasive follow up of the LV remodeling; 4) an original animal model of IMR and ITR was developed with the percutaneous selective injection of ethanol. Specific geometrical distortions of both ventricles that resulted in IMR and ITR were found; 5) we showed that the expression of eNOS was correlated with the distance from the MI and thus the amount of stress. Conclusion: This data suggest that IMR and ITR are caused by a geometrical distortion of both atrioventricular valves and that this macroscopic remodeling was associated with an up-regulation of eNOS that may be correlated with an adapatative process of the stretched cardiomyocytes. 11 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table of Content Abstract ii Table of Contents ill List of Tables v List of Figures vi List of abbreviations vii Ackno-wledgements ix INTRODUCTION I BACKGROUND 2 1 : ISCHEMIC HEART FAILURE WITH MITRAL AND TRICUSPID REGURGITATION 2 I -1 : Heart Failure : A Maj or Health Problem. 2 1-2: Ischemic Heart Failure 3 1-3: Ischemic Mitral Regurgitation 4 1-4: Functional Tricuspid Regurgitation in Cases of Ischemic Heart Failure 12 1 -5 : Surgical Approach of Ischemic Heart Failure 16 2 : ULTRASTRUCTURE OF THE MYOCARDIUM 24 2-1: The Sarcomere 24 2-2: Myocardial Excitation-contraction Coupling 26 2-3 : Sarcomere Stretch and Cardiac Function 27 AIM OF THE STUDY 30 EXPERIMENT I: A UNIFIED FUNCTIONAL TERMINOLOGY FOR THE MITRAL AND TRICUSPID VALVES 34 1: BACKGROUND: ANATOMY OF THE HUMAN MITRAL AND TRICUSPID VALVES 34 I -1 : Mitral Valve Anatomy 34 1-2: Tricuspid Valve Anatomy 44 2: MATERIALS AND METHODS 48 3: RESULTS 52 3-1 : The Leaflets and Their Commissures 52 3-2: The Papillary Muscles and Chordae Tendinae 53 3-3: Proposed Terminology and Classification 55 4: DISCUSSION 58 4-1: A New Nomenclature for the Tricuspid Valve 5 8 4-2: Clinical Relevance and Limitations of the Study 61 EXPERIMENT 2: GEOMETRICAL CHANGES OF THE MITRAL AND TRICUSPID VALVES DURING THE CARDIAC CYCLE 64 1: INTRODUCTION 64 2: MATERIALS AND METHODS 64 2-1 : Definition of the Different Phases of the Cardiac Cycle 64 2-2: Digital Sonomicrometry 65 2-3 : Data Acquisition 66 2-4: Surgical Preparation 67 111 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2-5: Definition of Anatomical Regions 70 2-6: Measurement and Statistical Analysis Methods 72 3: RESULTS 72 3-1 : Geometrical changes in Tricuspid and Mitral annuli 73 3-2: Geometrical Changes in Tricuspid and Mitral Annulo-papillary Muscle Planes 85 3-3: Geometrical Changes in the Mitral and Tricuspid Papillary Muscle Planes 97 4: DISCUSSION 103 4-1 : Mitral and Tricuspid Valve Annuli 103 4-2: Annulo-papillary Muscle Apparatus of Mitral and Tricuspid Valves 105 4-3 : Papillary Muscle Motion 108 EXPERIMENT 3: COMPARISON OF SONOMICROMETRY AND TTE DATA IN SHEEP 110 1 : TRANS-THORACIC ECHOCARDIOGRAPHY IN SHEEP 110 2 : MATERIALS AND METHODS 110 2-1 : Echo Data Acquisition 110 2-2: Surgical Experiment 111 2-3: Statistical Analysis 112 3: RESULTS 112 3 -1 : Data Comparison 112 3-2: Correlation of Trans-thoracic Echocardiography and Sonomicrometry Measurements 116 4: DISCUSSION 118 EXPERIMENT 4: PERCUTANEOUS INDUCTION OF A POSTERO-LATERAL INFARCT BY INJECTION OF 100% ETHANOL AND ANALYSIS OF LV AND RV GEOMETRICAL CHANGES. 121 1 : REVIEW OF EXISTING ANIMAL MODELS OF HEART FAILURE 121 1-1: Heart F ailure Induced by T oxin 121 1-2: Heart Failure Induced by Rapid Pacing 123 1 -3 : Heart Failure Induced by Ischemia 124 2: MATERIALS AND METHODS 126 2-1 : Induction of the Myocardial Infarction 126 2-2: Data Acquisition and Follow-up 127 2-3 : Macroscopic and Histology Analysis 128 2-4: Statistical Analysis 129 3: RESULTS 129 3-1: Percutaneous Induction of Myocardial Infarction 129 3 -2 : Development of Ischemic Cardiomyopathy 132 3-3: Histology Analysis 137 4: DISCUSSION 139 EXPERIMENT 5: CHANGE IN ENOS AND NNOS EXPRESSION BY DISTANCE FROM THE INFARCT IN AN OVINE ISCHEMIC HEART FAILURE MODEL 145 IV Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1 : NITRIC OXIDE SYNTHASE 145 1-1: Background 145 1-2: Nitric Oxide Synthase and the Heart 147 2: MATERIALS AND METHODS 152 2-1 : Preparation of Tissue 152 2-2: Protein isolation, SDS-polyacrylamide gel electrophoresis
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