Basic Cardiac Electrophysiology for the Clinician, Second Edition

352 Pages·2009·25.98 MB·English

by  Jose Jalife

Basic Cardiac
Electrophysiology
for the Clinician
Basic Cardiac Electrophysiology for the Clinician, 2nd edition
José Jalife, Mario Delmar, Justus Anumonwo, Omer Berenfeld, Jérôme Kalifa
© 2009 José Jalife, Mario Delmar, Justus Anumonwo, Omer Berenfeld and Jérôme Kalifa ISBN: 978-1-405-18333-8
Dedications
To Paloma, Andrea, David, Marina, Obi, Kachi, Celina, Sofía, Ilán,
Sebastián, Josyane, Jean-Pierre and Late Chief C.N. Anumonwo,
the Iyase of Ogwashi-Uku, Delta State, Nigeria.
Basic Cardiac
Electrophysiology
for the Clinician
Second Edition
José Jalife, MD
The Cyrus and Jane Farrehi Professor of Cardiovascular Research
Professor of Internal Medicine
Professor of Molecular & Integrative Physiology Co-Director
Center for Arrhythmia Research
University of Michigan
Ann Arbor, Michigan
USA
Mario Delmar, MD, PhD
Frank Norman Wilson Professor of Cardiovascular Medicine
Professor of Internal Medicine
Molecular & Integrative Physiology Co-Director, Center for Arrhythmia Research
University of Michigan
Ann Arbor, Michigan
USA
Justus Anumonwo, PhD
Assistant Professor of Internal Medicine
Cardiovascular Medicine
University of Michigan
Ann Arbor, Michigan
USA
Omer Berenfeld, PhD
Assistant Professor of Internal Medicine and Biomedical Engineering
Cardiovascular Medicine
University of Michigan
Ann Arbor, Michigan
USA
Jérôme Kalifa, MD, PhD
Assistant Professor of Internal Medicine
Cardiovascular Medicine
University of Michigan
Ann Arbor, Michigan
USA
A John Wiley & Sons, Ltd., Publication
This edition fi rst published 2009, © 2009 by José Jalife, Mario Delmar, Justus Anumonwo, Omer
Berenfeld and Jérôme Kalifa
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Library of Congress Cataloging-in-Publication Data
Basic cardiac electrophysiology for the clinician / Jose Jalife . . . [et al.]. – 2nd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4051-8333-8
1. Heart–Electric properties. 2. Electrophysiology. 3. Arrhythmia. 4. Heart conduction system.
I. Jalife, Jose.
[DNLM: 1. Heart–physiology. 2. Electrophysiology. WG 202 B3107 2009]
QP112.5.E46B37 2009
612.1′71–dc22
2008045638
ISBN 9781405183338
A catalogue record for this book is available from the British Library.
Set in 9.5 on 12 pt Palatino by SNP Best-set Typesetter Ltd., Hong Kong
Printed & bound in Malaysia
1 2009
Contents
Acknowledgments, vii
Foreword to the Second Edition by Douglas P. Zipes, ix
Foreword to the First Edition by Douglas P. Zipes, xi
Introduction, 1
Chapter 1 Bioelectricity, 7
Chapter 2 Ion Channels, 43
Chapter 3 Ion Channel Regulation, 72
Chapter 4 Impulse Initiation and Propagation in Cardiac Muscle, 92
Chapter 5 Rate Dependency of Discontinuous Propagation, 121
Chapter 6 Basic Mechanisms of Cardiac Arrhythmias, 152
Chapter 7 Rotors, Spirals, and Scroll Waves in the Heart, 191
Chapter 8 Rotors and the Mechanisms of Atrial Fibrillation, 224
Chapter 9 Molecular Mechanisms of Ventricular Fibrillation, 254
Chapter 10 Inheritable Arrhythmogenic Diseases, 276
Bibliography, 316
Index, 335
v
Acknowledgments
Special thanks to the Jalife, Delmar, Anumonwo, Berenfeld and Kalifa families
for their love, patience and unconditional support. We are also deeply indebted
to all students, postdoctoral fellows, and technicians who throughout the
years have contributed their work and ideas to our research program. Many
of the concepts presented in this book are direct results of such contributions.
We particularly thank all the current scientists, technicians, and clerical staff
of the Center for Arrhythmia Research of the University of Michigan for their
exceptional courage in following our lead and for sharing our vision for a
bright future in the study of intercellular communication and cardiac impulse
propagation. The unreserved support of our fearless administrator, Laurie
Lebouef, is greatly appreciated. Thanks to Sherry Morgenstern, our in-house
artist who helped with the fi gures. Our thanks go also to Doug Zipes, who
generously took time from his busy schedule to read the manuscripts and
write the forewords for the two editions of this book. We are obliged to
Dr. David Pinsky, Dr. Hakan Oral, and Dr. Fred Morady and to the leadership
of the University of Michigan Health System for helping make our dream for
a Center for Arrhythmia Research a reality with a bright outlook. Much of the
work presented was made possible by generous grants from the National
Heart, Lung and Blood Institute; National Institutes of Health; the American
Heart Association, Inc.; and the Heart Rhythm Society for the last 28 years.
José Jalife, MD
Mario Delmar, MD, PhD
Justus Anumonwo, PhD
Omer Berenfeld, PhD
Jérôme Kalifa, MD, PhD
vii
Foreword to the Second Edition
A popular series of books includes the words for dummies in the title, to indi-
cate the information contained has been modifi ed so that readers—certainly
not dummies, just less knowledgeable about the topic—can more easily
understand the subject matter presented. In fact, writing such a book requires
the authors to have an even greater grasp of the material than other experts
in the fi eld because they must be able to explain complex concepts in ways
the uninitiated can understand. This is accomplished by eliminating jargon
and superfl uous information characteristic of usual scientifi c writing, and
explaining the “taken for granted” information in detail, i.e., focusing on the
core of the topic for the less sophisticated student. Judging by the enormous
success of the series, the concept is effective. In fact, Dr. Jalife and his col-
leagues wrote such a book about basic cardiac electrophysiology 10 years ago
and have now updated and richly illustrated it with the wealth of new infor-
mation attained in the last decade. As they indicate in the Introduction, the
book is for all types of students of the heart—medical students, residents,
fellows, postdocs, and faculty, whether basic or clinical—to educate and inter-
est them in understanding cardiac electrophysiology and arrhythmias. It goes
without saying that the basic scientist early in his or her career would be
interested in such a book: I wish I had one when I started 40 years ago. But
what needs to be said is that the clinician should be interested in this topic as
well because acquiring this knowledge, even in its rudimentary form, will
enable him or her to be more effective in critically evaluating published lit-
erature, understanding the basis of various clinical syndromes and arrhyth-
mias, and, in the end, making more intelligent diagnostic and therapeutic
decisions. From a personal perspective, I think I have been a better clinician
because of my understanding of basic cardiac electrophysiology, knowledge
“from cell to bedside.” In the fi nal analysis, the goal of virtually every medical
scientist and physician is to provide better care for patients. This book brings
the doctor closer to achieving that end and I recommend it to every student
of the heart.
Douglas P. Zipes, MD
Distinguished Professor of Medicine, Pharmacology and Toxicology
Director, Division of Cardiology and Krannert Institute of Cardiology
Indiana University School of Medicine
ix
Foreword to the First Edition
Finally a book for the clinician that explains basic cardiac electrophysiology!
Pepe Jalife and his colleagues have done it at last, based on a series of lectures
they presented to residents, fellows, and faculty members of the divisions of
cardiology and pediatric cardiology at SLTNY Health Science Center in Syra-
cuse, New York. Their course, “Basic Cardiac Electrophysiology for Clinical
Fellows,” became exceedingly popular as clinicians realized the importance
of what they were learning and that this information could help them make
decisions, which directly impacted on choices for patient care. This type of
lecture series, with its subsequent book, could only be given by a group of
scientists with feet fi rmly planted in the animal laboratory and at the bedside.
Indeed this group of electrophysiologists represent precisely that skill set.
Further, they do this in a fashion that eschews the jargon of the profession
that ordinarily is certain to drive off would-be students. The importance of
their teaching is underscored by the breakthrough observations over the past
several years on the genetic basis for the “ionopathy” responsible for the
congenital Long QT Syndrome. Knowledge of this type will increment and
include more and more diseases as we hurdle toward the 21st century and
the practice of genetic-based medicine. A fi rm grasp of the electrophysiologi-
cal basis of the principles for the normal and abnormal heartbeat will be
required, and Basic Cardiac Electrophysiology for the Clinician provides this
information. Their work is very much “all you need to know, as clinicians,
about basic cardiac electrophysiology but were afraid to ask.” Each chapter
has a similar format, beginning with an introduction and ending with a
summary. I found that very helpful, and so should the clinician. Further, the
fi gures avoid complexity and vividly make the points the authors seek to
convey.
Chapter 1 deals with the bioelectricity of cardiac electrophysiology and
discusses how the laws of electricity apply to movement of ions across cell
membranes, using standard concepts about voltage, current, resistance, and
capacitance. Basic concepts of action potentials and their differences in muscle,
sinus and AV nodes, and Purkinje fi bers help explain many of the clinical
phenomena observed. There is a useful discussion on methodology to
xi
xii Foreword to the First Edition
understand which currents fl ow through the various ion channels, such as
use of voltage clamp method. Finally, the concept of rectifi cation can be
understood!
Chapter 2 introduces the various components responsible for the currents
underlying cardiac excitation that are carried by ion channels, pumps or
exchangers, and the differences between them. Gating and ion selectivity are
discussed along with the various currents and the molecular structure of
cardiac ion channels. The M and H gates, postulated by Hodgkin and Huxley,
are explained in the light of the three confi rmational states of closed, open
and inactivated ion channels.
In Chapter 3 the authors present mechanisms of ion channel regulation,
including enzyme systems, signaling pathways and autonomic regulation of
ionic currents. Understanding control of ion channel regulation may provide
insight into methods of therapeutic intervention when these systems
go awry.
Chapter 4 offers a critical discussion of the concept of propagation of the
cardiac impulse, explaining how the electrical signal spreads from cell to cell
through the cardiac synctium to induce electrical activation of the entire heart.
This chapter capitalizes on the basic information presented in the previous
three chapters. A key concept, electrotonus, is clearly explained.
Intrinsic to the heartbeat is the concept of pacemaker activity, with the sinus
node as the obvious prototypic example. Chapter 5 considers in-depth sinus
node function, the synchronization of all of the sinus node cells to discharge
in unison, phase response curves and entrainment and resetting, along with
vagal modulation of sinus node activity. Many of these concepts are then
applied to parasystolic foci and electrotonic modulation.
Chapter 6 focuses on rate dependent modulation of discontinuous action
potential propagation, a concept underlying complex patterns of propagation
such as Wenckebach and development of arrhythmias such as fi brillation.
Most investigators are unaware that propagation, when viewed microscopi-
cally, is actually step wise as electrotonic currents propagate from cell to cell.
Macroscopically, the action potential appears to travel uniformly and con-
tinuously. Differences in cell geometry and ionic currents, as well as non-
uniform distribution of gap junctions connecting neighboring myocytes,
contribute to non-uniform discontinuous propagation.
Chapter 7 is “bread and butter” for any clinical electrophysiologist and
discusses clearly and at length the cellular mechanisms underlying the basic
for cardiac arrhythmias. Thus, abnormal impulse formation, including normal
and abnormal automaticity and triggered activity, along with alterations in
conduction of the cardiac impulse that provide the basis for reentry, underlie
all the therapeutic interventions used to treat patients with arrhythmias.
Chapter 8 extends these concepts by focusing in on spiral wave activity,
which may be the basis for functional reentry. This chapter, to me, emphasizes
a major aspect of the contributions from the Syracuse group of electrophysi-
ologists: their insights into mechanisms of cardiac electrophysiology are
Foreword to the First Edition xiii
rooted in “biological laws of nature,” from phase response curves and reset-
ting of parasystolic foci to spiral wave activity. One can only do this if the
investigators have a clear understanding of the fundamental electrical phe-
nomena responsible for the genesis of the heartbeat. Jalife and his group
clearly demonstrate this breathtaking expanse of knowledge and it comes
through vividly to the reader in chapter after chapter. This book is an exciting
contribution for anyone interested in cardiac electrophysiology.
Douglas P. Zipes, MD
Distinguished Professor of Medicine, Pharmacology and Toxicology
Director, Division of Cardiology and Krannert Institute of Cardiology
Indiana University School of Medicine