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Xerox University Microfilms INFORMATION TO USERS This material was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1.The sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. You will find a good image of the page in the adjacent frame. 3. When a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It is customary to begin photoing at the upper left hand corner of a large sheet and to continue photoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again — beginning below the first row and continuing on until complete. 4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. Silver prints of "photographs" may be ordered at additional charge by writing the Order Department, giving the catalog number, title, author and specific pages you wish reproduced. 5. PLEASE NOTE: Some pages may have indistinct print. Filmed as received. Xerox University Microfilms 300 North Zeeb Road Ann Arbor, Michigan 48106 75-3149 MUIR, D.V.M.» William Wallace, III, 1946- ARRHYTHMIAS— THEIR DETERMINANTS AND PREVENTION IN ASSOCIATION WITH THIOBARBITURATES AND HALOTHANE ANESTHESIA. The Ohio State University, Ph.D., 1974 Physiology Xerox University MicrofilmsAnn , Arbor, Michigan 48106 ( THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED. ' ARRHYTHMIAS - THEIR DETERMINANTS AND PREVENTION j IN ASSOCIATION WITH THIOBARBITURATES AND HALOTHANE ANESTHESIA DISSERTATION Presented in Partial Fulfillment of the Requirements for ! the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By William Wallace Muir III, B.S., D.V.M., M.S. ***** The Ohio State University 1974 Reading Committee: Approved By Dr. Robert L. Hamlin Dr. Thomas E. Powers Dr. Roger A. Yeary Dr. Jean Hensel TCdvTser Department of Veterinary Physiology 5 Pharmacology acknowledgements I am extremely grateful to Professor Robert L. llamlin for his untiring encouragement and support of this study. His constructive critisisms and interest in cardiac rhythm were of great help in the completion of this work. A special work of thanks to M s . Linda Werner for her skilled technical assistance throughout all phases of this study. Her organization and coordination of labora­ tory facilities were greatly appreciated. I thank Mr. Ron McClean for his aid in the arrange­ ment and completion of many of the figures. This thank you is extended to the entire photography area associated with the Ohio State University College of Veterinary Medicine. I am very grateful to the Department of Veterinary Physiology and Pharmacology for the financial support and especially to Drs. Jean Hensel and Thomas Powers for their analytical critisisms and suggestions. Sincere thanks are due Mrs. Ricki Bishop for the accuracy, high quality and speed with which she completed the typing of this text. I am indeed grateful to Mrs. Karen Rosenberry for her clinical support. Her assistance in the teaching and ii service areas of clinical veterinary anesthesia gave me added time to complete this work. Finally, I wish to acknowledge my wife Cheryl for her support and patience in the many hours spent studying and preparing this transcript. VITA July 8, 1946 . Born, Bay City, Michigan 1968 ............. B.S., Michigan State University, East Lansing, Michigan 1968-1970........ Member of Open Heart Surgery Team Michigan State University, East Lansing, Michigan 1970-1974 ........ Teaching Associate, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 1 9 7 1 ............. M.Sc., The Ohio State University, Columbus, Ohio PUBLICATIONS Exploratory Measurements of Arterial Flow in Horses. Jon A. Rumberger, David R. Gross, William W. Muir, III, Gary L. Geiger, Robert M. Nerem and Robert L. Hamlin. October, 1972. J. Biomed. Eng. Respiratory Fluctuations in Durations of Phases of Ven­ tricular Systole in the Dog. William M. Muir, D.V.M., M.Sc. and Robert L. Hamlin, D.V.M., Ph.D. May, 1973. J.A.V.M.R., 647-651. Right and Left Ventricular Systolic Intervals During Ventilation and Sinus Arrhythmia in the Dog: Genesis of Physiologic Spliting of the Second Heart Sound. Robert L. Hamlin, D.V.M., Ph.D., William W. Muir, III, D.V.M., M.Sc., David R. Gross, D.V.M., M.S., Frank S. Pipers, D.V.M., M.Sc., January, 1974, J.A.V.M.R., 6-13. FIELDS OF STUDY Major - Veterinary Physiology and Pharmacology. Studies in Cardio-Pulmonary Physiology Robert L. Hamlin, D.V.M., Ph.D., Adviser iv TABLE OF CONTENTS Page ACKNOWLEDGEMENTS i i VITA.................................................. iv LIST OF TABLES....................................... vi LIST OF F I G U R E S ....................................vii INTRODUCTION............ • ......................... 1 Chapter I. REVIEW OF LITERATURE ...................... 5 Determinants of Arrhythmia Formation Thiobarbiturates and Arrhythmias Atropine and Arrhythmias Halothane and Arrhythmias Phenothiazines and Arrhythmias Experimental Models for Arrhythmia Production II. MATERIALS AND METHODS..........................65 III. RESULTS........................................78 IV. DISCUSSION .................................. 126 V. SUMMARY................. 145 BIBLIOGRAPHY........................................ 158 v LIST OP TABLES Table Page 1. Techniques Used in the Production of Cardiac Arrhythmias.......... 56 2. Mean Heart Alterations After the Initial Pressure Peak Due to the Administration of Epinephrine Intravenously ................ 110 3. Minimum Maximum and Mean Dose of Epinephrine (ugm) Needed to Produce a Dysrrythmia ..................... Ill 4. Effect of Alterations in Mean Arterial Blood Pressure on the Dosage of Epinephrine Needed to Produce Multifocal Ventricular Tachycardia (MVT) After Admini­ stration of Surital and Halo th a n e ...........118 5. Effect of Acetylpromazine (0.5 mg/lb) on Cardiac Mean Blood Pressure and Heart Rate in Unanesthetized D o g s ........... 124 6. Mean and Standard Error Values for Venous Blood Gas Samples in Groups 1 through 9 ................................ 125 7. Mean Arterial Pressure Alterations After the Initial Pressure Peak Due to the Administration of Epinephrine Intravenously.... .......................... 140 vi LIST OF FIGURES Figure Page X. Diagramatic Representation of the Phases of the Action Potential in Automatic and Non-automatic Cardiac Tissues......................................... 7 2. Diagramatic Representation of the Effects of Halothane on Canine Cardiac Fibers... ............................ 38 3. Basic Structure of the Phenothiazine Molecule and Several of its Derivatives. 44 4. Diagramatic Representation of the Effects of Phenothiazines on Canine Cardiac Fibers... ............................ 49 5. Classification of Arrhythmias Associated with the Administration of Epinephrine and Anesthesia................. 76 6. Control Electrocardiagram and Response to Varying Doses of Epinephrine in the Dog........................ 82 7. Relationship Between Heart Rate and Blood Pressure in the Unanes­ thetized Dog Given 20 ugm of Epinephrine.................................... 84 8. Effects of Epinephrine on the Relationship Between Heart Rate and Blood Pressure in Halothane Anesthetized Dogs Given Acetyl- promazine...................................... 91 9. Effects of Definitive Doses of Epinephrine on Cardiac Rhythm in Unanesthetized Do g s ........................ 93 vii LIST OF FI CURES-Continue cl Figure Page 10. Effects of Definitive Doses of Epinephrine on Cardiac Rhythm in Dogs as Influenced by Surital................. 95 11. Effects of Definitive Doses of Epinephrine on Cardiac Rhythm in Dogs as Influenced by Halothane............... 97 12. Effects of Definitive Doses of Epinephrine on Cardiac Rhythm in Dogs as Influenced by Surital and Halothane...................................... 99 13. Effects of Definitive Doses of Epinephrine on Cardiac Rhythm in Dogs as Influenced by Surital, Halothane and Atropine ..................... 101 14. Effects of Definitive Doses of Epinephrine on Cardiac Rhythm in Dogs as Influenced by Acepromazine, Surital and Halothane........................ 103 15. Effects of Definitive Doses of Epinephrine on Cardiac Rhythm in Dogs as Influenced by Surital, Halothane and Acepromazine................. 105 16. Three Dimensional Representation of Anesthetic Regimen vs. Dose of Epinephrine vs. Arrhythmia F o r m e d ....................................... 107 17. Specific Arrhythmias Associated With Various Anesthetic Regimens and Dosages of Epinephrine.................. 109 18. Effect of the Pressor Agent Phenylephrine
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