The Slow Inward Current And Cardiac Arrhythmias (developments In Cardiovascular Medicine)

Since Paul Cranefield published his monograph, The Conduction of the Cardiac Impulse, in 1975, much has been learned about the role of the slow inward current in cardiac electrophysiology. Because of this expanse in know­ ledge, both basic and clinical, it appeared reasonable to review in a mono­ graph once again what was known. When Martinus Nijhoff first approached us to undertake the task of updating this information, we were initially reluctant for several reasons. First, we did not feel that the subject could be adequately and thoroughly reviewed, from the cell to the bedside, by a single person. Second, time constraints on all of us precluded even attempting such a task. However, we were encouraged by several of our friends (' egged on' one might even say, since they wished the job done but did not want to do it themselves!) who promised faithfully to contribute chapters on time if we accepted the task. So we did, and most of them did also. Front Matter....Pages I-XIII Front Matter....Pages 1-1 Historical Perspective....Pages 3-9 The Slow Response and Cardiac Arrhythmias....Pages 11-21 Front Matter....Pages 23-23 Voltage Clamp Studies of the Slow Inward Current....Pages 25-95 The Slow Inward Current: Non-Voltage-Clamp Studies....Pages 97-110 The Role of Cyclic AMP in Regulation of The Slow Inward Current....Pages 111-126 The Role of the Slow Inward Current in Impulse Formation....Pages 127-148 Slow Conduction in the Heart....Pages 149-171 Slow Inward Current and Contraction....Pages 173-203 Effects of Neurotransmitters on the Slow Inward Current....Pages 205-219 Changes in Membrane Electrical Properties during Development of the Heart....Pages 221-262 Front Matter....Pages 263-263 The Slow Inward Current of the Rabbit Sino-Atrial Nodal Cells....Pages 265-284 The Slow Inward Current and AV Nodal Propagation....Pages 285-294 The Slow Response in Human Atrium....Pages 295-308 The Slow Response in Human Ventricle....Pages 309-326 The Role of Electrotonus in Slow Potential Development and Conduction in Canine Purkinje Tissue....Pages 327-355 Voltage Modulation of Automaticity in Cardiac Purkinje Fibers....Pages 357-373 Depolarization-Induced Automaticity in AtriaL and Ventricular Myocardial Fibers....Pages 375-396 Front Matter....Pages 397-397 Role of the Slow Current in the Generation of Arrhythmias in Ischemic Myocardium....Pages 399-416 Digitalis-Induced Delayed Afterdepolarizations....Pages 417-435 Triggered Activity....Pages 437-454 Front Matter....Pages 397-397 Effect of Antiarrhythmic Drugs on the Slow Inward Current System....Pages 455-477 Front Matter....Pages 479-479 The Role of the Slow Inward Current in the Genesis And Maintenance Of Supraventricular Tachyarrhythmias In Man....Pages 481-506 The Role of the Slow Inward Current in the Genesis of Ventricular Tachyarrhythmias in Man....Pages 507-514 Back Matter....Pages 515-521 Cardiac Dynamics is the name of a relatively young field of study, born from the fruitful interaction between branches of two different disciplines: medicine and physics.'Dynamics'is the branch of physics which deals with the action of forces on bodies or particles in motion or at rest.'Cardiac'relates to the clinical field of cardiology but also to cardiophysiology, both of which are specialized branches of medicine. Narrower than the well­ established field of Hemodynamics, Cardiac Dynamics is restricted to dynamic phenomena occurring in and around the heart. The mathematical treatment of such phenomena, however, is vastly more complex because of the intricate nature of the mechanisms involved in the cardiac action. Thus, whereas hemodynamics is concerned with predominantly passive (visco-) elastic structures - vessels - containing time-variant flow of viscous flui- blood -, the mechanical study of the heart requires additional con­ siderations such as: active elastic components representing the contractile mechanism of cardiac muscle, complex geometry and fiber structure in the myocardial wall, autoregulatory mechanisms, and intricate flow patterns associated with valve motion. Viewed in this light it is not surprising that attempts to describe ventricular pump function and to quantify contractile performance have not reached the level of sophistication which is common in e. g. arterial hemodynamics. For the same reason, many of the often simplified approaches to describe ventricular mechanics failed to stand up to more rigorous theoretical, experimental or clinical testing. The VIth World Symposium on Cardiac Pacing in Montreal 1979 opened with a course, meant to be an introduction for newcomers and an updating re­ fresher and link between the various fields of knowledge needed by experienced persons for cardiac pacing. Invited guest lecturers were selected for their world recognized expertise in the individual subjects. This book is a collection of the various presentations on historical, clinical, electrophysiological and technical aspects of cardiac pacing. Together they cover the fundamentals of cardiac stimulation. We hope that this book may become an introductory guide to the field of cardiac pacing and that it may contribute to a better understanding of the pacemaker system and a better treatment of the pacemaker patient. Claude C. Meere Hilbert J. Th. Thalen ACKNOWLEDGEMENT The editors of 'Fundamentals on Cardiac Pacing' acknowledge the under­ standing and support of their families, during the long nocturnal hours and weekends during which this book was prepared. A special note of appreciation is extended to our secretaries, especially Mrs. Carolyn Gaarenstroom-Arriens and Miss Katrien Schuurman for their 'emergency typing' and Miss Lynn Bacon and Mr. Boudewijn Commandeur from Martinus Nijhoff Publishers, who succeeded in completing the book in time for the Montreal meeting. Only those involved are able to realize the importance of their contribution. CONTRIBUTORS David L. Bowers, B.S.E.E., Vitarel Inc. San Diego, California, U.S.A. Guy Fontaine, M.D., Groupe Hospitalier, Pitie-Salpetriere, Paris, France This book represents tangible results of the Institute of Applied Physiology and Medicine's objectives of bringing into clinical application the concepts and results of bioengineers and physiologists. lt has grown out of our experience in development of original Doppler diagnostic instrumentation and its application to more than 6,000 patients in non-invasive diagnosis of the extracranial cerebrovascular circulation. It gath­ ers together bioengineering and physiological concepts which were initially developed for a graduate course for physicians and specialized medical tech­ nicians. lt should be of particular interest to physicians and medical technol­ ogists whose specialties lie in the field of neurology, vascular surgery, and radiology. The particular selection of techniques on our complete cerebrovascular non-invasive evaluation was chosen primarily to provide an integrated approach relying primarily on Doppler ultrasonic audio signals, but in addition utilizing a pertinent history and physical examination of the patient. The examination is performed by a specially trained physiology technician. Suffi­ cient data is provided to the interpreting physician who develops a consulta­ tive report for the referring physician. The ultimate objective is prevention of stroke and symptoms of cerebrovascular insufficiency. The Doppler functional information supplements the angiography anatomical management decisions for angiography and surgery, anti-platelet or anti-coagulant medication, or to follow the patient with no special treatment. This Symposium is the third of a series of scientific meetings in the field of echocardiology, held at the Erasmus University Rotterdam. • The series was initiated by Klaas Born, who organized the first two meetings with great success. These followed the procedure of two days of parallel sessions with invited speakers only. This time, we decided to broaden the basis of the meeting and have a three-day program of parallel sessions, combining invited papers, free com­ munications and posters. We decided, however, to maintain one of the most striking features of the last meeting- having the complete proceedings available at the time of the meeting. We confronted the authors-to-be with a very tight schedule in order to make the book a true reflection of the state of the art in echocardiology. As a'result, editing time was also very limited and neither terminology nor units have been completely standardized. This book has three main parts. The first, and largest, part consists of contributions on echocardiology in adults, and is divided into four sections. The first section is a general survey of various applications, whereas the remaining three centre round specific applications, i.e. ischemic disease, left ventricular function and cardiac valves, respectively. The second part con­ tains applications in pediatric cardiology; due to the wide variety of topics covered, no particular subdivision has been made. The last part of the book is devoted to instrumentation, methods and new developments. During the past decade enormous progress has been made in the development of new cardiovascular drugs and in our understanding of the clinical pharma­ cology and the pharmacokinetics of old drugs. In addition, newer applications of older agents have emerged. For example, vasodilators such as nitroglycerin are now being employed in the treatment of congestive heart failure, and anti­ hypertensives such as bretylium are used in the management of ventricular arrhythmias. Individual chapters in this book focus on (1) the clinical pharmacology and pharmacokinetics of the individual drugs, and (2) the clinical applications of these drugs, with attention also to serum concentrations, pathophysiology, and drug interactions where appropriate. The contributors to this text have labored to provide the reader with a meaningful, practical update on the clinical uses and usefulness of cardioactive drugs. We are deeply grateful to each of them for their generous participation in this endeavor. LEONARD S. DREIFUS, M.D. ALBERT N. BREST, M.D. 1. ANTIARRHYTHMIC AGENTS LEONARD S. DREIFUS and JOEL MORGANROTH Ideally, the management of cardiac arrhythmias must be predicated on (1) complete elucidation of the genesis of the various rhythm disturbances, and (2) a full understanding of the pharmacologic action of individual antiarrhythmic agents. Only with this precise information does it become possible to administer a particular agent or agents specifically effective against a given arrhythmia. Hypertension is a major health problem and contrary to ischemic heart disease, which occurs only in Western countries, its distribution is almost universal. It is this universality that has prompted us to gather, in this book, data on arterial blood pressure obtained in different parts of the world. Moreover, cerebrovascular mortality, which is the commonest cause of death from hypertension, is decreasing in most Western countries and in Japan, and the reasons for this are still far from clear. A major problem in comparing blood pressure values from different centers is the standardization of the measurement. Complete standardization will never be achieved if one takes into account the numerous factors that may influence blood pressure in epidemiological studies. Whether blood pressures are measured by doctors or by technicians, are recorded at home, in the working place or in a hospital, in sitting, standing or supine position, and is taken during the same examination-all of these whether a blood sample factors can influence blood pressure measurement. But meals, time of day (blood pressure being higher in the evening), heart rate, cuff size, stethoscope used, digit preference, month of year, temperature, etc., can equally influence the measurement. Home reading of arterial blood pressure at standardized times is probably the best answer to all of these problems and has been used with gratifying results in a comparative study between Belgium and Korea. Edited By Charles T. Lancée. Symposium Held At Erasmus University, Rotterdam, June 1979, And Organized In Association With The Interuniversity Institute Of Cardiology, Amsterdam Et Al. Includes Bibliographical References And Index. Edited By Leonard S. Dreifus And Albert N. Brest. Includes Bibliographical References And Index. Edited By H. Kesteloot And J.v. Joossens. Includes Bibliographical References And Index.