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This updated second edition provides a comprehensive overview of cardiac pathology. Clear illustrations of the common styles of dissection are provided along with the normal anatomy and histology. The chapters cover autopsy heart examination, ischemic heart disease, myocarditis, sudden death, valvular disease, transplant pathology, cardiomyopathy, cardiac neoplasia and congenital heart disease with a clear analysis of diagnostic criteria (macroscopic, microscopic and genetic) for both common cardiac diseases and those of less common types. The text is accompanied by high quality macroscopic and microscopic images and references to other specialty data sources. Cardiac Pathology: A Guide to Current Practice is aimed at established pathologists and trainees, as well as any clinician with an interest in cardiac disease. It will be of value to those working in cardiac surgery, cardiology and those in the autopsy/forensic fields.

This book highlights the multifaceted roles of Reactive Oxygen Species (ROS) in modulating normal cellular and molecular mechanisms during the development of different types of heart disease. Each chapter in the book deals with the role that altered redox homeostasis plays in the pathophysiology of heart disease. In addition, the book explains how reactive oxidant species interact with their targets and provides novel strategies for attenuating oxidative stress-induced types of heart disease.The book not only covers ROS-induced response in heart disease at the cellular level, but also demonstrates that an imbalance of redox states has its roots in our genes, and explains the ways gene expression is regulated. In turn, it reviews potential sources of ROS, their pathological effects on the heart, and potential sites for therapeutic interventions.

Advances in cellular physiology and molecular biology have now disclosed the metabolic changes and adaptational responses of the heart to various kinds of stresses. Topics covered in this volume include the regulation of myocardial proteins in mechanical overload, the alteration of adrenoceptors in the stressed heart, metabolic adaptation in cardiac hypertrophy, intracellular calcium metabolism in the ischemia-reperfused myocardium, calcium overload as a cause of myocardial stunning, acquisition of ischemic tolerance by ischemic preconditioning, factors that accelerate myocardial injury, and ventricular remodeling in the ischemic heart. As an update of the latest findings in basic cardiology, this book will benefit both researchers and clinical practitioners.

could go on for several pages. Thus the book edited This book emphasizes the fundamental, functional aspects of cardiology. Within the last thirty years, by Sperelakis IS a potent reminder of the almost for­ the rift between clinical and investigative cardiology gotten fact that cardiology has twO sites, inextrica­ has widened, because of the overwhelming devel­ bly related. opment of new clinical procedures, both diagnostic The book deals with subjects in which Dr. Sper­ and therapeutic. Almost forgotten is the fact that elakis has pioneered: ultrastructure of heart muscle, we owe most of the clinical advances to theoretical electrophysiology, cardiac contractility, and ion ex­ and experimental observations. I need not remind change. An extension of these subjects is the chapter the reader of the work of Carrel, who performed the dealing with fundamental topics of the coronary cir­ first experimental coronary bypass in 1902, or the culation. work of the brothers Curie in 1880, both physicists, This book is indeed a timely reminder of the im­ who discovered piezoelectricity, the keystone in ech­ portance of the fundamental aspects of cardiology. ogradiography; of the works of Langley, who intro­ Emphasis on clinical aspects of cardiology alone will duced the receptors concept; of Ahlquist in 1946, result in a sterile and unproductive future for a field who first differentiated between alpha and beta re­ that has made such stunning advances during the ceptors; of Fleckenstein, a physiologist who pi­ last thirty years to the benefit of millions of people.

Cardiac disorders are an exciting area of classic pathology and recently defined disease. Cardiac Pathology: A Guide to Current Practice discusses the various disorders and also provides a backdrop of developmental embryology, diagnostic imaging and current therapeutics. Cardiac Pathology: A Guide to Current Practice aims to deliver in bench-book format a comprehensive overview of cardiac pathology that is relevant to those practicing in surgical pathology and autopsy arenas. Clear illustrations of the common styles of dissection are provided along with the normal anatomy and histology. Chapters cover the approach to the autopsy heart, ischemic heart disease, myocarditis, sudden death, valvular disease, transplant pathology, cardiomyopathy, cardiac neoplasia and congenital heart disease with a clear analysis of diagnostic criteria (macroscopic, microscopic and genetic) for both common cardiac diseases and those of rare format. The text is accompanied by high-quality macroscopic and microscopic images and references to other in-depth specialty data sources. Although aimed in particular at pathologists, Cardiac Pathology: A Guide to Current Practice should also be of value to cardiologists, cardiothoracic surgeons and other professions allied to medicine.

A variety of metabolic processes are known to be intimately involved in the maintenance of cellular structure and function. It has also become clear that metabolic events involved in the synthesis and hydrolysis of ATP as well as for the synthesis of proteins and phospholipids are essential for cellular health. The regulation of cell function is generally achieved through participation of a wide variety of hormones and different signal transduction mechanisms for the activation/deactivation of some specific metabolic processes. In this regard cyclic AMP and calcium seem to play a crucial role. Various hormones are also known to affect the genetic machinery of all the cell; however, the exact signals for genetic control of cellular function are not well defined. In particular, the sequence of events concerned with remodelling of different types of cells under various pathological situations is poorly understood. In this book we have therefore dealt with some of these issues from biochemical, molecular biological, physiological, and pharmacological viewpoints. Special emphasis has been laid on understanding heart function and metabolism in health and disease in general, and cardiac hypertrophy, heart failure, and ischemic heart disease in particular. It is hoped that this multidisciplinary information will be of value to basic scientists and clinical investigators.

The Stressed Heart is truly unique in concept and will provide an eXCItmg adventure to the reader no matter what his or her field of expertise and interest. The title, although quite appropriate, does not adequately indicate the range of topics considered or the rational interrelationships among them. Indeed, perhaps the most important point to be learned from the book is that a serious consideration of the response of the heart to mechanical overload, ischemia, or excessive humoral stimuli must include evaluation of each of the topics in the table of contents. The heart responds to stress through alterations in both structure and function. How these changes are brought about is the subject of the initial chapters. These consider first the normal regulation of gene expression in the heart, the rapid response to mechanical overload that leads to both quantitative and qualitative changes in the contractile proteins, and our current understand­ ing of the signals that might be elicited by stress and alter gene expression. One chapter emphasizes the fact that, regardless of the nature of the stress, the common denominator is a discrepancy between energy requirements and expenditure. The central role of cellular acidosis in initiating the sequence of responses to stress and the possible roles of peptide regulators of transcription and protein regulators of translation are considered in detail.

Over two centuries ago, oxygen was discovered as'air vital': the component of the earth's atmosphere necessary for life. Less than five years after this discovery, it was found that oxygen was both a life-sustaining and life threatening inhalant as it plays a role in the two extremes of the animal kingdom: life and death. In the subse­ quent years, we have made major strides in understanding the role of oxygen in maintaining life and volumes of information are now available on this topic. Our knowledge of the contribution of oxygen in cellular dysfunction and cell death which for the most part had lagged behind has begun to catch up. The deleterious ef­ fects of oxygen radicals and activated oxygen species on a variety of biological systems have now been described. Recently attention has also been focused on the toxic effects of oxygen on the cardiovascular system. The major aim of the present treatise is to offer an integrated view of the pathophysiological aspects of oxygen toxicity in the heart and blood vessels coupled with a review of therapeutic approaches (hopes?) with free radical scavengers and antioxidants. Internationally known expert investigators provide a concise and critical review on the topic of their expertise which also contains data from their own research.

Knowledge of cardiac ion channels and transporters has advanced remarkably in the last two decades with the development of patch-clamp and molecular biological techniques. This textbook offers a comprehensive overview of structures and functions of ion channels and transporters in the heart. Readers are first introduced to the molecular biology and electrophysiology of all the important ion channels. After discussing their developmental changes, the pharmacology and pathophysiology of clinically-relevant ion channels are reviewed. Molecular aspects of the cardiac excitation-contraction coupling and intracellular Ca2+ regulation by ion transporters are also described. The book will be useful to electrophysiologists, cardiac physiologists and pharmacologists, and molecular biologists interested in ion channels at all levels. For research specialists, the book will provide a perspective of the field. The book can be used as a reference source for working scientists in the fields of ion channels, biophysics, cardiac electrophysiology, and pharmacology. It is aimed at graduate and medical students, designed for use as a textbook for graduate and medical courses.

This book is an edited compilation of the scientific presentations given at a symposium on cardiovascular hemodynamics and the contemporary practice of cardiology which was organized in Malta, April 1989. The field of cardio­ vascular medicine has undergone an extraordinary explosion of knowledge regarding the basic biology of the heart and circulation in health and disease, as well as technologic innovations for probing and assessing cardiac geometry and physiology. This edition addresses such issues which are key problems in current management of patients with heart disease. For example, the classic notion that severe myocardial ischemia is invariably followd by either recovery of normal function or the progression to cell death has been challenged by experimental studies and clinical observations of patients undergoing throm­ bolysis and revascularization. This growing body of observations clearly indicates that the consequences of ischemia and reperfusion are much more complex and variable, and include several states of abnormal metabolism and contractile function which are distinct from either'health'or'death'. This book presents current issues of both consensus and controversy regarding the effects of myocardial ischemia and reperfusion, including irreversible cell loss (infarction), myocardial stunning, and myocardial hibernation. Particular attention is paid to the assessment and differentiation of such patients in the coronary care unit, catheterization suite, or following surgical revascula­ rization. Secondly, this book addresses the hemodynamic evaluation of the patient with valvular heart disease in today's cardiology practice.

During the last decade we have witnessed a rapid expansion of our knowledge of the role of the endothelium in the control of vascular tone and hemostasis. In paricular, developments in molecular biology have enabled us to understand its physiology in greater detail. Furthermore, it is now clear that dysfunction of the endothelium contributes to various cardiovascular diseases. This is especially true for the coronary vascular bed. Development of atherosclerosis, disturbed vasomotor tone in stable ischemic syndromes, and the interaction of thrombocytes with the endothelium in acute ischemic syndrome are all consequences of endothelium dysfunction. Also, secondary changes in endothelial function have been described, for instance in chronic heart failure. This monograph reviews the present knowledge of the role of the endothelium in the control of coronary flow. The authors lead the reader through this topic starting at the basic physiology of endothelial function and the principles of coronary flow regulation. Next, the use of modern clinical techniques to evaluate endothelial function such as positron emission tomography and angioscopy are discussed. Subsequently, several pathophysiological processes and the role of endothelium are addressed. Finally, the interaction of various presently used cardiovascular drugs with the endothelium is indicated. It is the combination of basic sciences with clinical observations in this book which may be appreciated by a large number of scientists and physicians active in the field of cardiovascular disease. It is also this combination of different disciplines which will determine future developments and new avenues in pharmacotherapy involving the endothelium.

The first edition of this book was quite successful. As in the first edition, the book is divided into two major sections: cardiac muscle and coronary circula­ Several complimentary book reviews appeared soon tion. The book is multidisciplinary and includes after the first edition was published, and written and membrane biophysics, electrophysiology, physiol­ oral words of praise and appreciation were given both ogy, pathophysiology, pharmacology, biochemistry, to the publisher and to me by quite a few individuals. and ultrastructure. Thus, the book attempts ro It is because of such positive comments and reactions that the publisher and I decided to embark on a integrate all relevant aspects of the factors influenc­ second edition of Physiology and Pathophysiology of the ing the function of the heart as a vital organ under Heart. The second edition was long in preparation, normal and various abnormal conditions. The book taking over a year to complete. All chapter contri­ also attempts to set the foundation for an under­ butors were asked to revise, improve, and update standing of the action and mechanism of action of a their articles, and all have done so with enthusiasm number of classes of cardioactive drugs.

Nature is totally amoral! There are at least 3-4 million people in France alone who suffer from arterial hypertension, and whose cardiovascular system is submitted day and night to both a haemodynamic and hormonal stress. In all cases, the vasculature hypertrophies as does the myocardium. This growth process is obviously mainly detrimental at the outset since it lowers compliance of the arteries and makes them stiffer. In contrast, myocardial hypertrophy is initially beneficial since the growth process multiplies the number of contractile units and by so doing improves external work. In addition, according to Starling's law, wall stress is lowered. Growth factors playa major role in this amoral process as a trigger for hypertrophy at the vascular level, and very likely at the level of the myocardium. Another major point of interest is the role of growth factors as determinants of restenosis after angioplasty and also of atherogenesis. Several chapters in this book are directly or indirectly concerned with this problem which is far from being purely academic since several groups are currently trying to control these processes by gene transfer. Certainly, one of the major clinical questions arising from such studies is why restenosis is not more frequent in clinical practice. After de-endotheliazation, the biologist would predict on the basis of recent studies on growth factors, and in contrast with current clinical opinion, that hypertrophy would occur in all cases with more or less complete restenosis.

Potassium channels (K+) are membrane-spanning proteins which serve many important functions and are becoming a hot topic in physiology. K+ channels determine or modulate many functions of vascular smooth muscle, endothelial and inflammatory cells, and thus are central to regulation of arterial tone and control of cell proliferation. They are also promising targets for antihypertensive treatments with drugs which open and close specific types of K+ channels, making for an active field of research. With their ability to control vascular tone, voltage-gated K+ channels play a significant role in both pulmonary and systemic hypertension as well as in cardiac arrhythmias. This book will highlight the latest discoveries by leading researchers pertaining to the role of K+ channels in the heart and blood vessels in normal physiology and a variety of disease states.

This special issue of Molecular and Cellular Biochemistry good source of information in this regard. contains original research papers as well as invited reviews We wish to thank all of the contributors for their help and dedicated, on the occasion of the 40th anniversary of the in­ cooperation. We also wish to thank Mrs. Verona Kuhle for auguration of the Heart Research Group in Beriin-Buch that her secretarial help. We are grateful to Dr. Naranjan S. Dhalla, today forms a part there ofthe Max Delbriick Center for Mo­ Editor-in-Chief of Molecular and Cellular Biochemistry for his lecular Medicine, to Professor Albert Wollenberger, founder interest and encouragement, and for agreeing to publish this of the Heart Research Group and for 21 years its head. issue in honor of Albert Wollenberger. The papers in this issue are written by researchers work­ ing in the field of cardiovascular research who together with ERNST-GEORG KRAUSE and ROLAND VETTER Albert Wollenberger share the belief that an integrative ap­ Max Delbriick Center for Molecular Medicine plication of advances in molecular and cellular biology will Robert-Rossle-StraBe 10 lead to new concepts for treatment and prevention of cardio­ 13122 Beriin-Buch vascular diseases. We hope that this special will serve as a Gennany ALBERT WOLLENBERGER, Professor, Ph. D. (Harvard), Dr. Sc. Med. (Berlin) The dedication is accorded to Prof.

The original series, Advances in Prostaglandin Research, edited by Sultan M. M. Karim, was published by MTP Press in three volumes in 1975 and 1976. A glance at those books illustrates the progress that has been made since then. The thromboxanes were mentioned twice (first publication 1975) and prostacyclin not once (first publication 1976); leukotrienes were only on the horizon. The amazing generation of research data in the last 10-15 years has given new, broad insights into many areas, including asthma, inflammation, renaL cardiovascular and gastrointestinal diseases and in reproduction, and has led in some instances to real clinical benefit. This series, Advances in Eicosanoid Research, reflects the current understanding of prostaglandins, thromboxanes and leukotrienes. The aim is to provide an introductory background to each topic and the most up-to-date information available. Although each book stands alone, the eicosanoids cut across many boundaries in their basic actions; selected chapters from each book in the series will provide illuminating and productive information for all readers which will advance their education and research. In the production of this series, I must acknowledge with pleasure my collaboration with editors and authors and the patient endeavours of Dr Michael Brewis and the staff at MTP Press.

This book contains the manuscripts of the majority of the papers given during the symposium'Improvement of Myocardial Perfusion'which was held from Sep­ tember 27-29,1984 in Mainz/Germany. It has been the purpose of this meeting to focus the interest of scientifically and clinically interested cardiologists on the new developments in this field. We therefore chose the subtitle'Medical-Mechanical -Surgical Approach'. The medical improvements in myocardial perfusion have been brought about by the application of streptokinase, urokinase and tissue-type plasminogen ac­ tivator in the first hours after the onset of an acute myocardial infarction. The different modes of application and the possibilities to evaluate and eventually to quantify the results of these treatments were addressed during the first part of the meeting. The mechanical way to improve perfusion nowadays mainly consists of the application of intracoronary balloon angioplasty. Although since 1977 the treat­ ment has become a routine method, several questions are still open such as the exact mode of action, the reaction of the vessel wall, the optimal pressure and balloon size as well as the long term results and the prevention of restenosis.

This book addresses the entire cardiologicalpathology, and accompanies the reader through each significantcondition, from incidence and severity, tomechanisms, clinical and lab diagnosis, and up totreatment and prognosis.The presentation is enhanced by the use of numerous tables and figures, to better illustrate the similarities and differences between the discussed entities. The chapters have an uniform structure fostering a methodical approach to heart disease. The level is intermediate, with an accent on clinical practice. At the same time, an excellent tool for preparing for exams, as i) disease mechanisms are systematically discussed; ii) guidelines are explained and summarized; iii) novel resarch directions are explained. The book provides conciseness, completeness, and updatedness, while offers: for residents, familiarization with the discipline of cardiology; for cardiology fellows, the book will be a friendly companion for practice and Boards study; for primary care physicians, the book represents an update to their knowledge; while for clinical cardiologists, the book represents a companion reference.

Mitochondria have been pivotal in the development of some of the most important ideas in modern biology. Since the discovery that the organelle has its own DNA and specific mutations were found in association with neuromuscular and cardiovascular diseases and with aging, an extraordi-nary number of publications have followed, and the term mitochondrial medicine was coined. Furthermore, our understanding of the multiple roles that mitochondria play in cardiac cell homeostasis opened the door for intensive experimentation to understand the pathogenesis and to find new treatments for cardiovascular diseases. Besides its role in adenosine triphosphate generation, mitochondria regu-late a complex network of cellular interactions, involving (1) generation and detoxification of reactive oxygen species, including superoxide anion, hy-drogen peroxide, and hydroxyl radical; (2) maintenance of the antioxidant glutathione in a reduced state and adequate level of mitochondrial matrix superoxide dismutase; (3) cytoplasmic calcium homeostasis, particularly under conditions of cellular calcium loading; (4) transport of metabolites between cytoplasm and matrix; (5) both programmed (apoptosis) and necrotic cell death; and (6) cell growth and development. It is therefore not surprising that this organelle has come to be the center stage in many current investigations of cardiovascular diseases, aging, and agi- related disease. Concomitant with these advances, an impressive effort is under- way for the development of new tools and methodologies to study mitochondrial structure and function, including powerful ways to visualize, monitor, and alter the organelle function to assess the genetic consequences of these perturbations.