This provides background information on procedures, epidemiological aspects, problem areas, mortality and morbidity risk. These topics are of particular interest for investigators in ECG research and clinical trials. This monograph is specialized beyond the scope of ordinary clinical textbooks of electrocardiography that have traditionally flooded the market. The authors have closely collaborated for over a quarter of a century in operating an academic ECG Center.

This wide ranging work provides a complete representation of the present state of knowledge of the vascular endothelium. The volume comprises 20 chapters by experts who have made significant contributions to research in the vascular endothelium. The text discusses the structure, development and function of the normal vascular endothelium, considers conditions that lead to the disruption of vascular physiology and provides a comprehensive description of pathologies and their treatment.

Cardiovascular diseases continue to be the leading cause of death in the - jority of industrialized countries. The most frequent underlying pathology, namely atherosclerosis, and its clinical sequelae, namely coronary heart d- ease, cerebrovascular disease and peripheral artery disease, remain common although for a long time we have been made aware of avoidable or mo- ?able etiological factors such as smoking, fat-rich diet or lack of exercise, and although these adverse lifestyle factors have been extensively addressed by population-wide primary prevention programs. Cardiovascular morbidity and mortality also remain high despite successful anti-hypertensive and lipid lowering drug therapies which help to reduce cardiovascular morbidity and mortality by about 30% in both secondary and tertiary prevention settings. This can partly be explained by the increasing life expectancy and growing p- portionofelderly people,especiallyinEuropeandNorthAmerica. Inaddition, the World Health Organization makes the alarming prediction that probably in response to the spreading of western dietary behavior and lack of exercise resulting in an increasing prevalence of diabetes, dyslipidemia and hypert- sion, cardiovascular diseases rather than infectious diseases will become the most frequent cause of death worldwide. This volume of the Handbook of Experimental Pharmacology entitled "Atherosclerosis" is divided into four parts and intends to give an overview on the pathogenesis of atherosclerosis, established treatment and prevention regimen, and of perspectives for the development of new treatment modalities.

It is often suggested that the incidence of cancer and coronary heart disease could be much reduced or even eliminated if only people would stop smoking cigarettes and eat fewer high-cholesterol foods. The evidence, however, shows that such views are simplistic and unrealistic and that, instead, cancer and CHD are the product of many risk factors acting synergistically. Psychosocial factors (stress, personality) are six times as predictive as smoking, cholesterol level or blood pressure and much more responsive to prophylactic treatment. This book admits that, while smoking is a risk factor for cancer and CHD, its effects have been exaggerated. A more realistic appraisal of a very complex chain of events incorporating many diverse factors is given, and appropriate action to prevent cancer and coronary heart disease is discussed.

Since it was introduced less than 100 years ago, analysis of the circulatory response to exercise as a measure of cardiac function has undergone remarkable development. Most recently this approach has incorporated the burgeoning technology of the last half of the 20th century to meet the physiological and diagnostic needs of scientist and clinicians. The ease of administration, economy and abundant data that characterize exercise testing for its relative staying power as the most frequently utilized noninvasive method of cardiovascular evaluation. The basic modalities of exercise electrocardiography of treadmill and bicycle have been extended by noninvasive cardiac imaging techniques, including scintigraphy and echocardiography, that have provided new insights in myocardial function during exertion and pharmacologic stress. At the same time, traditional exercise electrocardiography has also been refined by innovations that have broadened its applications. Exercise Testing: Current Concepts and Recent Advances affords the reader a state-of-the-art presentation of the diverse and expanding methods of exercise testing and their roles in patient management. The contributors to this volume include individuals who have made seminal contributions to the field during the last several decades. Indeed, it is legitimate to designate this group as a Who's Who of Exercise Testing'. It is our hope that this book will enhance the reader's understanding of contemporary methods of exercise testing, as well as provide a glimpse into future directions of this science, that this knowledge is applied to optimal diagnosis and management of our patients.

Rotary blood pumps increasingly are being used in open heart surgery and in assisted circulation for patients with heart disease. These rotary devices include vortex (centrifugal) and axial pumps, which can be utilized in conditions where the use of conventional pulsatile pumps would entail problems of cost and size. Rapid progress is now being made in developing new devices for controlling blood flow within the heart and great vessels as well as extracorporeally for use in coronary and intensive care units and, in the future, for long-term use. This book provides information on the physiology of nonpulsatile circulation, the development of rotary pump engineering, and the clinical application of rotary blood pumps. It also presents an overview of future developments in this important field.

Cardiac performance is regulated not only by cardiac muscle properties but also by several other factors, including those associated with the neurohumoral system and the mechanical characteristics of the peripheral circulation. New information con cerning these regulatory factors has furthered our understanding of the pathophysi ology of cardiac dysfunction. However, controversy remains, along with a need to integrate these multidisciplinary findings. It was with this in mind, together with my continuing interest in the response of the normal and diseased heart to variations in loading conditions, that the satellite symposium entitled "Interactions Between Car diac Function and Vascular Dynamics" was organized and dedicated to my mentor, Dr. T. Takishima. The symposium was held in Fukushima, Japan, in 1992 following the Tenth Inter national Conference of the Cardiovascular Systems Dynamics Society in Kobe, Japan, which was organized by the then president of the society, Dr. Masatsugu Hori. The Fukushima symposium and the Kobe conference were stimulating and informative. To commemorate these events, Dr. Hori, Dr. Janicki, and I decided to publish this book. It covers topics that were presented then as well as pertinent new material. As a result, the book includes not only updated reviews but also up-to-date findings that were not considered at the two scientific sessions. The high level attained in this book is due to the outstanding contributions from internationally renowned scientists. This final product of their efforts should prove to be a valuable source of information to the reader.

The aim of the Textbook of Cardiovascular Prevention and Rehabilitation is to provide practical guidance for all cardiologists and other health personnel engaged in the management of cardiac patients. The book will follow the concept of "seamless care service," i.e. a streamlined combination of preventive and rehabilitative methods in order both to add years to life and life to years. It will consist of eight sections.

Commencing with an introductory section it will focus on guidelines, prevention, risk stratification and the evidence base of cardiac rehabilitation. In the following three sections different models for exercise testing and training, nutritional counselling and smoking cessation will be presented. The behavioral section contains health-related quality of life and psychological issues, patient education, compliance and adherence to the treatment program. In the social section the return to work, the role of relatives, heart foundations etc. will be discussed.

Groups with special needs will be highlighted in the seventh section, which will address children with cardiac disease, elderly, women, heart failure and cardiac transplantation patients, patients with ICD or after valve surgery. The final section comprises evaluation options. quality assurance and organisational matters i.e. program design, staff training, safety, documentation and a health-economic cost review; even national program differences will be debated.

Each section will contain a short summary and tables with practical guidance statements. Furthermore, all sections will be formatted as to follow the natural course of cardiovascular disease, starting off with focus on primary preventivecare and finishing with the demands on rehabilitation of the patient with advanced disease, thus following the "seamless care" concept.

The ATP-sensitive potassium channel (KATP) was discovered in 1983. Since then, an enormous amount of research has been undertaken to characterize it in detail. This volume consolidates both the current knowledge and most recent advances on the subject, and its relationship to myocardial protection. To this end, the editors have assembled investigators at the forefront of ongoing basic and clinical research to provide scholarly and candid comments concerning each of the pertinent issues, including: a comprehensive review of the biology of the channel with respect to the structure-activity relationship as well as overall chemistry of the channel; the role of opening this channel and its effect on smooth muscle (covering both the effects on myocardial stunning and its ability to protect against myocardial infarction); the relationship of KATP channel opening and the protection to the myocardium afforded by the phenomenon of ischemic preconditioning; the relationship between the KATP channel and electrophysiological consequences with specific reference to arrhythmogenicity; and the clinical implications of the use of agents that mimic the opening of this channel, with reference to its protective nature and its use in the treatment of angina. Audience: Clinicians and basic scientists who have a direct interest in the KATP channel as well as those groups who are interested in the entire concept of myocardial protection and its relationship to academic and clinical medicine.

The prevalence of hypertension is almost three times as high as that of diabetes mellitus type 2, with both conditions being major risk factors for stroke, ischemic heart disease, cardiac arrhythmias, and heart failure. The exact prevalence of hypertension related to hormonal derangements (endocrine hypertension) is not known but estimated to affect less than 15% of hypertensive patients. Recent scientific discoveries have increased the understanding of the pathophysiologic mechanisms of hypertension. In Endocrine Hypertension, a renowned panel of experts provides a comprehensive, state-of-the-art overview of this disorder, discussing when to assign an endocrine cause in one of many conditions that may present with hypertension. The first part of Endocrine Hypertension is dedicated to adrenal causes. The second part of the volume concerns potential nonadrenal causes of hypertension, such as growth hormone excess or deficiency, primary hyperparathyroidism, vitamin D deficiency, testosterone deficiency, insulin resistance, obesity-associated hypertension, and the role of central mineralocorticoid receptors and cardiovascular disease. An important contribution to the literature, Endocrine Hypertension is an indispensable reference not only for endocrinologists, diabetologists, and adrenal investigators, but also for translational scientists and clinicians from cardiology, internal medicine, pediatrics, family medicine, geriatrics, urology, and reproductive medicine / gynecology.

In the past decade, major progress has been made in understanding mec- nisms of arrhythmias. This progress stems from much-improved experim- tal, genetic, and computational techniques that have helped to clarify the roles of speci?c proteins in the cardiac cycle, including ion channels, pumps, - changer, adaptor proteins, cell-surface receptors, and contractile proteins. The interactions of these components, and their individual potential as therap- tic targets, have also been studied in detail, via an array of new imaging and sophisticated experimental modalities. The past 10 years have also led to the realization that genetics plays a predominant role in the development of lethal arrhythmias. Many of the topics discussed in this text re?ect very recently undertaken research directions including the genetics of arrhythmias, cell signaling mo- cules as potential therapeutic targets, and traf?cking to the membrane. These new approaches and implementations of anti-arrhythmic therapy derive from many decades of research as outlined in the ?rst chapter by the distinguished professors Michael Rosen (Columbia University) and Michiel Janse (University of Amsterdam). The text covers changes in approaches to arrhythmia therapy over time, in multiple cardiac regions, and over many scales, from gene to protein to cell to tissue to organ.

Role of Potassium in Preventive Cardiovascular Medicine: Information related to this question has accumulated for nearly a hundred years, from work in cellular physiology, experimental studies in animals, clinical trials, and from population and epidemiological investigations. Because of the importance of integration of this diverse body of information, the most significant findings are brought together in this book. This body of information provides emphatic support for the importance of high dietary potassium intake as a means of reducing the risk of cardiovascular diseases, as it provides abundant evidence that potassium depletion has significant, deleterious influences that increase the risk of hypertension, atherosclerosis, heart failure, and stroke. At this time we have the results and data required to strongly recommend dietary modification to increase potassium intake. But making the recommendation will only be the first step; convincing the population to undertake the change in eating patterns will be challenging, and will require concerted actions by government, the medical community, and the food and beverage industries. The outcome promises to be well worth the investment. This book is an excellent source of current information on the many roles of potassium in cardiovascular disease. It succinctly mixes basic physiology and clinical aspects in a manner that will make it of great value to both researchers and clinicians.' Norman M. Kaplan, M.D., Professor of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX

Mechanisms of Heart Failure is based on papers selected from poster presentations made at the International Conference on Heart Failure, Winnipeg, May 20-23, 1994. Although the entire book is one continuous discussion of subcellular mechanisms of heart failure and its treatment, the presentation has been divided into three sections: the opening section on the subcellular basis of heart failure includes discussions of cytokines, signal transduction, metabolism, extracellular matrix, organ level changes and newer approaches to understanding the pathogenesis of heart failure. The second section focuses on the pathophysiological aspects of cardiomyopathies and their treatment. In the final section, medical, surgical and pharmacological approaches to the treatment of heart failure are discussed in clinical and animal laboratory settings.

This second edition of the book on Store-operated Ca2+ Entry Pathways has been updated with the newest discoveries that emerged in the field within the last five years. The crystal structure of the Ca2+ signaling core complex is described which adds to a new understanding of the molecular interactions involved. Each chapter has been revised and extended. The book retains its interdisciplinary approach and supplies biochemists, cell biologists and biophysicists as well as clinicians in immunology, neurology and cardiology with valuable information on Ca2+ signaling mechanisms, functions, dysfunctions and their consequences.

This book contains 55 chapters that summarize referred to the special issue of Drug Development lectures given during the Fifth International Research (Volume 31, Number 4, April 1994). Symposium on Adenosine and Adenine Measured by the number and quality of presenta- Nucleotides held in Philadelphia, Pennsylvania, tions, and by the record number of participants, U. S. A. , May 9-13, 1994. The symposium and the Fifth International Symposium on Adenosine its proceedings follow four previous symposia and Adenine Nucleotides was clearly an intel- and their published proceedings. Previous sym- lectually stimulating meeting. It is safe to posia were held in Banfff, Canada (1978), conclude that the purine research field is vibrant Charlottesville, Virginia (1982), Munich, and still growing. Adenosine has rapidly become Germany (1986), and Lake Yamanaka, Japan the drug of choice for the acute management (1990). of supraventricular tachyarrhythmias and was The program included a wide range of sub- recently approved for use in combination with jects from molecular and cellular biology to cardiac imaging for detection of ischemic heart clinical applications. Great emphasis was placed disease. Additional clinical applications of on cutting edge information derived from studies adenosine and adenosine-related drugs and ATP using molecular and cellular biology techniques seem closer than ever before. The editors would like to express their grati- applied to the field of adenosine and adenine nucleotide research. Likewise, the program tude to the distinguished contributors for their included a number of presentations on poten- excellent chapters and to all participants.

In 1962, 30 years after the discovery by du Vigneaud have pathologic consequences. One potentially sig- of a new sulfur amino acid, homocysteine; Carson and nificant health outcome of such mild to moderate Neil reported two siblings with mental retardation in hyperhomocysteinemia is an increased risk of occlu- northern Ireland with elevated urinary homocystine. sive vascular disease. Homocysteine concentrations in Nearly simultaneously, Gerritsen and Waisman patients with vascular disease were, on average, 31 % greater than in normal controls. Prospective assess- identified increased homocystine in the urine of a mentally retarded infant in Wisconsin. Within two ment of vascular disease risk among men with higher years, Harvey Mudd, James Finkelstein, and their homocysteine concentrations indicated that plasma coworkers at the National Institutes of health (USA) homocysteine at only 12% above the upper limit of that the enzyme cystathionine ~- normal levels was associated with a 3. 4-fold increase had reported synthase was lacking in a liver biopsy specimen from in risk of acute myocardial infarction. Studies from another patient with homocystinuria. This was the original Framingham Heart Study cohort (USA) the first indication of a vitamin relationship to have shown strong, positive correlation between homocystinuria, because that enzyme has as its co- plasma homocysteine concentration and degree of factor vitamin B6 (pyridoxal phosphate). Thereafter, carotid stenosis.

Since the first pacemaker implantation in October 1958 by Senning and Elmqvist in Sweden, cardiac pacing for bradycardia has become a well-established therapy. The impressive growth of clinical experience and the rapid development of pacemaker devices have greatly contributed to this situation. The electrical therapy appears to be so easy that insertion of the lead and its connection to the pacemaker generator requires little effort, skill or insight. However, after implantation a patient's condition seldom remains stable, which requires a flexible pacing program to cover all new cardiac events, and broad insight from clinician and technical colleagues. The Pacemaker Clinic of the 90's teaches anatomical and electrophysiological aspects of pacing, supports the prevention of complications, and points to new developments in the field. Apart from classical indications for cardiac pacing, the book discusses the validity of the latest indications, supporting the cardiologist and the associated professional in selecting the appropriate pacing mode and pacemaker follow-up in individual patients. The Pacemaker Clinic of the 90's will be a helpful companion for years to come.

That precursors of adult coronary artery disease, hypertension, and type II diabetes begin in childhood have been clearly established by the Bogalusa Heart Study. This unique research program has been able to follow a biracial (black/white) population over 35 years from childhood through mid-adulthood to provide perspectives on the natural history of adult heart diseases. Not only do these observations describe trajectories of cardio-metabolic risk variables leading to these diseases but provide a rationale for the need to begin prevention beginning in childhood. The trajectories of the burden of cardio-metabolic risk variables in the context of their fetal origin and chromosome telomere dynamics provide some insight into the metabolic imprinting in utero and aging process. The observed racial contrasts on cardio-metabolic risk variables implicate various biologic pathways interacting with environment contributing to the high morbidity and mortality from related diseases in our population. To address the seriousness of the onset of cardiovascular disease in youth, approaches to primordial prevention are described focussing on childhood health education as an important aspect of Preventive Cardiology.

In 1962, Thomas Kuhne coined the term "paradigm shift" while arguing that human knowledge advances by quantum leaps with interspersed smaller steps. Preparation for the major advance is generally not a concerted effort by thought leaders. Rather, a few (or one) visionaries gain insights into a process and are able to definitely demonstrate the accuracy of their worldview. Often, the epiphany does not occur during the intellectual lifetime of the discoverers. Medicine has had numerous such "paradigm shifts" including the compelling reworking of Galen's concepts of the body. Of note, the scientific world of the time explained the new views by arguing that the human body must have changed between the time of ancient Greece and modern Europe. The inauguration of cardiac surgery itself required profound shifts in medicine's view of physiology. Yet, over the ensuing 40 years, the field was fine tuned so we could provide greater than 95% success rates in elective surgery with low cost and short h- pital stays. In some parts of the world, the procedures were viewed as commodities and prices dropped as providers were unable to differentiate the quality of their work. As patients and their physicians became more demanding, the desire to make the procedures "minimally invasive" grew. In effect, what we were really searching for was a life saving procedure that also preserved quality of life. In short, "minimally invasive" has really been a code phrase for procedures that disrupt our quality of life the least.

This volume sets out to consider a range of cardiac diseases for which drugs may play a therapeutic role by virtue of their effects on aspects of the immune system. The book reviews diseases of the heart which may involve an immunopharmacological component, and methods and techniques for the study of physiological and biochemical functions in the heart. An important focus is the immunopharmacology of the coronary vascular endothelium and the role of cellular and biochemical components of the immune system in the pathogenesis of atherosclerosis. The content also includes a review of the use of immunologically relevant agents in the setting of cardiac transplantation from aclinical perspective. Immunotherapy has a definite role to play in cardiology to a greater or lesser extent than other forms of intervention, depending on the type of cardiac disease. Immunopharmacology of the Heart aims to identify and clarify this role and points to potential developments of the future. Immunopharmacology of the Heart is a volume for the SYSTEMS theme of The Handbook of Pharmacology. In common with all other volumes it contains standardized illustrations and terms/abbreviations (glossaries of illustrations and terms published at the back of the volume). Other topics covered include: Leukocytes and their role in ischaemic heart disease. Complement activation. Sudden cardiac death. The stunned myocardium and reperfusion injury.

One of the major biomedical triumphs of the post-World War II era was the defmitive demonstration that hypercholesterolemia is a key causative factor in atherosclerosis; that hypercholesterolemia can be effectively treated; and that treatment significantly reduces not only coronary disease mortality but also all cause mortality. Treatment to lower plasma levels of cholesterol - primarily low density lipoprotein (LDL) cholesterol - is now accepted as best medical practice and both physicians and patients are being educated to take aggressive measures to lower LDL. We can confidently look forward to important decreases in the toll of coronary artery disease over the coming decades. However, there is still uncertainty as to the exact mechanisms by which elevated plasma cholesterol and LDL levels initiate and favor the progression of lesions. There is general consensus that one of the earliest responses to hypercholesterolemia is the adhesion of monocytes to aortic endothelial cells followed by their penetration into the subendothelial space, where they differentiate into macrophages. These cells, and also medial smooth muscle cells that have migrated into the subendothelial space, then become loaded with mUltiple, large droplets of cholesterol esters . . . the hallmark of the earliest visible atherosclerotic lesion, the so-called fatty streak. This lesion is the precursor of the more advanced lesions, both in animal models and in humans. Thus the centrality of hypercholesterolemia cannot be overstated. Still, the atherogenic process is complex and evolves over a long period of time."

Complex physiopathological relationships have been proven to exist between two of the body's most vital organs; the brain and the heart. In Cell Cycle Regulation and Differentiation in Cardiovascular and Neural Systems Antonio Giordano, Umberto Galderisi and a panel of the most respected authorities in their field offer an in-depth analysis of the differentiation process in two systems that have profound relationships with one another. The text looks at several aspects of the cardiovascular and nervous systems from a new point of view, describing the differences and similarities in their differentiation pathways with an emphasis on the role of cell cycle regulation and cell differentiation. Topics discussed include neurogenesis in the central nervous system, neural stem cells, and the basic-helix-loop-helix transcription factors in neural differentiation. Ground-breaking and authoritative, Cell Cycle Regulation and Differentiation in Cardiovascular and Neural Systems is a must have for all researchers in cardiovascular medicine and neuroscience and will prompt the scientific community to perceive cell cycle regulation and differentiation under a novel and more comprehensive light.