Bøger i Developments in Cardiovascular serien

This book is based on the papers presented at the Workshop on "Rehabilitation of the Visually Impaired" held in Flo­ rence at the Institute for the Research on Electromagnetic Waves of the Italian Research Council on April 4-6, 1984. The Workshop, sponsored by the Committee for Medical and Public Health Research of the Commission of the European Communities, was meant to exchange ideas about the need, importance and feasibility of a European cooperation in the field of visual impairment and to identify promising research areas, where current national activities could take advantage of such a collaboration in order to increase their efficiency. In particular, it dealt with the develop­ ment and use of technical aids (mainly based on computers and signal processing techniques) and with the elaboration, evaluation and standardization of new methods and tests. The attendance was multidisciplinary, including researchers from the fields of technology, medicine and psychology and representatives from organizations involved in the rehabi­ litation of the visually impaired. Five technical sessions were organized, dealing with the following topics: automatic production of Braille and systems for paperless Braille, aids for reading and for the interaction with coded informa­ tion sources, low vision aids, transduction of visual infor­ mation into a tactile representation, mobility aids. Three different application sectors were mainly considered: education and culture, vocational training, mobility. A final session was devoted to a discussion in working groups. The results are briefly outlined in the following concise report of the Workshop.

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.

In recent years methods have been developed to study cardiac function, myocardial blood flow and myocardial metabolism with radionuclides. These developments have been facilitated through the introduction of new radiopharmaceuticals, the design of special gamma cameras and dedicated computer systems. However, part of the information provided by nuclear cardiology can also be obtained through other investigations such as echocardiography, exercise electrocardiography and cardiac catheterisation with ventriculography and coronary arteriography. Thus the practising physician must select the most appropriate methodes) of investigation for each patient. Such choices should be based on proper understanding of both the value and the restrictions of each method. In this book the state-of-the-art in nuclear cardiology is reviewed, including radionuclide angiography for analysis of left and right ventricu­ lar function and for measurement of shunts and regurgitation volumes, perfusion scintigraphy and other methods for measurement of myocardial bloodflow and metabolism and computer processing of radio nuclide Images. Each chapter has been written by an expert from either Europe or the USA, who has contributed to the developments in his particular field. The principles of each method of investigation are described, as well as the precautions that should be taken in order to obtain high quality data. Guidelines are provided for the interpretation ofthe data based on studies in various centers where the methods were developed and tested.

It is indeed ironical that in the absence of a complete knowledge of Pathophysiology, clinical cardiologists are left with no choice but to do the best they can to help the patient with the armamentarium of drugs at their disposal. But nothing could be further from truth than to treat the diagnosed end point of a disease process without a full understanding of its patho­ physiology. This point was eloquently made by Dr. Arnold Katz in his Presidential Address (Chapter 1) at the 8th Annual Meeting of the American Section of the International Society for Heart Research held in Winnipeg, Canada, July 8-11, 1986. This volume represents a part of the scientific proceedings of this Meeting. From a reading of this treatise it will become evident that discoveries of newer scientific facts as well as a better understanding of pathophysiology are continuously influencing/ improving our therapeutic approaches in modern medicine. In this book, latest biochemical, physiological and pharmacological findings on different experimental models such as Myocaridal hypertrophy, Hypertension and heart failure, Diabetes, Cardio­ myopathies and Cardiac function in shock are described by internationally recognised experts. Hopefully information presented here will provide another building block to the edifice of Science of Cardiology which we all are trying to create. Acknowledgements We are grateful to the following Agencies and Foundations for their generous financial support of the Symposium, which formed the basis of this book. A. Major Contributors: 1. Manitoba Heart Foundation 2. Sterling-Winthrop Research Institute 3. Squibb Canada, Inc.

This book is timely and challenging. Within its pages are commentaries and opinions on the scientific background and explanatory ideas for a complex of symptoms and investigations known as syndrome X. The commonest cause by far of angina pectoris is coronary artery obstruction due to atheromatous lesions both within the wall of the artery and intruding into the lumen; in such patients it is expected that there maybe ST segment depression on atrial pacing or on an exercise test indicating myocardial ischemia. Syndrome X was a term first used in an editorial written by Kemp in 1973. He was referring to patients in group X in a paper from Arbogast and Bourassa. Patients in group X had three features, namely angina as judged on a clinical history, alterations of the ST segment on the electrocardiogram during atrial pacing and smooth unobstructed coronary arteries (presumed normal) as assessed by the technique of coronary angiography. The changes on the electrocardiogram, conventionally indicative of myocardial ischemia, could not be explained on the basis of any abnormality of the coronary arteries and Kemp named the complex of fmdings syndrome X because of this seeming paradox and the lack of a single explanation. In the last thirty-one years there has been substantial scientific interest in this syndrome giving rise to a large number of publications. The name syndrome X has led to considerable confusion. Physicians are familiar with the X chromosome and with X linked congenital disorders.

Cardiovascular disease affects 20% of all Americans and is the leading cause of death in the USA. Every year approximately 1,500.000 Americans suffer from an acute myocardial infarction, and over 25% of the total number of deaths in this country are attributable to coronary artery disease. Unstable angina causes over 650,000 hospital admissions, and in the absence of medical therapy, the rate of progression from unstable angina to infarction is 12-20%. Since plaque disruption, plaque erosion, and acute intracoronary thrombus formation play major roles in the pathophysiology of both unstable angina and acute myocardial infarction, and since the two disease entities represent a continuum of coronary ischemic syndromes, it is appropriate to discuss the two disease states in a single monograph. Unstable Coronary Artery Syndromes, Pathophysiology, Diagnosis and Treatment will offer the clinician a reference book which coherently discusses the pathophysiology of acute ischemic syndromes as well as remarks diagnosis and treatment strategies. Geared toward internists and cardiologists, the book should allow the reader to understand the pathophysiology of unstable coronary artery syndromes and subsequently apply this knowledge to patient care.

Angioplasty has completely transformed the treatment of coronary artery disease and is widely used, with more than 800,000 procedures performed worldwide per year. However, the enthusiasm for angioplasty is shadowed by restenosis, which remains a critical problem after the procedure, resulting in clinical recurrence in over a third of patients. Recently, the mechanisms of restenosis have been completely reappraised with an enriched understanding that the original concept of neointimal hyperplasia may not be accounting for the bulk of the problem. There is a desperate need to heighten understanding of the remodeling process at the molecular, cellular, and arterial level. Vascular remodeling is a well established concept in the field of atherosclerosis and hypertension, but only in recent years has its applicability to the field of restenosis become pivotal. Accordingly, the editors perceived the need to assemble the first book dedicated to the concept of coronary artery remodeling in restenosis, in order to clearly review the experiments leading to the remodeling hypothesis and integrate this with the neointimal hyperplasia (tumor) model for the development of the restenotic lesion. The authors of this book present their experience to facilitate the understanding of the mechanisms for coronary restenosis and remodeling. The various experimental models, clinical issues, and basic mechanisms are reviewed in detail, resulting in a fresh approach to a vexing clinical problem. Arterial Remodeling: A Critical Factor in Restenosis will be useful to the physician and trainee who have an interest in restenosis, and specifically in the major pathophysiologic process which determines the fate of arterial healing in patients following percutaneous coronary revascularization. It is hoped that this book will lay the foundation for more effective therapies that will reduce the chance of constrictive remodeling and improve the long-term efficacy of non-surgical coronary revascularization in the future.

Coronary heart disease (CHD) remains a major cause of human mortality and morbidity worldwide. Classical risk factors for atherosclerosis fail to account fully for the wide variations in CHD prevalence and/or severity between differing populations. The search for hitherto unrecognised risk factors has recently focused on the potential role of chronic inflammation and common infections. Chronic Infection, Chlamydia and Coronary Heart Disease is the first book to review the wealth of evidence linking various infective agents with CHD, focusing particularly on the proposed pathogenetic role of the main candidate microorganism, Chlamydia pneumoniae. Written by two leading investigators in the field, the book provides a concise, clearly written and up-to-date account of the diverse lines of evidence - seroepidemiological, pathological, animal and in vitro data and clinical antibiotic trials. The possibility of an infective basis to atherosclerosis and CHD has already attracted much scientific interest. Chronic Infection, Chlamydia and Coronary Heart Disease highlights the key published works on the topic, and concludes with information on existing, ongoing, and future lines of enquiry.

In the past, coronary arteriography was the only modality available to provide high quality images of the coronary anatomy. Quantitative coronary arteriography (QCA) was developed, implemented, validated and extensively applied to obtain accurate and reproducible data about coronary morphology and the functional significance of coronary obstructions. Over the last few years extensive basic technological research supported by clinical investigations has created competing modalities to visualize coronary morphology and the associated perfusion of the myocardial muscle. Currently, the following modalities are available: X-ray coronary arteriography, intracoronary ultrasound, contrast- and stress-echocardiography, angioscopy, nuclear cardiology, magnetic resonance imaging, and cine and spiral CT imaging. For all these imaging modalities, the application of dedicated quantitative analytical software packages enables the evaluation of the imaging studies in a more accurate, reliable, and reproducible manner. These extensions and achievements have resulted in improved diagnostics and subsequently in improved patient care. Particularly in patients with ischaemic heart disease, major progress has been made to detect coronary artery disease in an early phase of the disease process, to follow the atherosclerotic changes in the coronary arteries, to establish the functional and metabolic consequences of the luminal obstructions, and accurately to assess the results of interventional therapy. Aside from all these high-tech developments in cardiac imaging techniques, the transition from the analogue to the digital world has been going on for some time now. For the future, it has been predicted that the CD-R will be the exchange medium for cardiac images and DICOM-3 the standard file format. This has been a major achievement in the field of standardization activities. Since these developments will have a major impact on the way images will be stored, reviewed and exchanged in the near future, an important part of this book has been dedicated to DICOM and the filmless catheterization laboratory. Cardiovascular Imaging will assist cardiologists, radiologists, nuclear medicine physicians, image processing specialists, physicists, basic scientists, and fellows in training for these specialties to understand the most recent achievements in cardiac imaging techniques and their impact on cardiovascular medicine.

Diabetes is a major public health problem which is expected to affect 160 million people worldwide by the year 2000. Clearly an understanding of the effects of diabetes on the heart is an important step in the development of strategies to reduce the incidence of heart disease for diabetic patients, thus increasing their overall life-expectancy and quality of life. In this book, the editors bring together the different lines of evidence supportive of the idea of a diabetic cardiomyopathy. The first chapter provides an overview of the impact of cardiac dysfunction on the mortality and morbidity of the diabetic population in general, as well as a presentation of clinical aspects of heart disease in diabetes. This is followed by chapters concerned with the pathological and functional changes that occur in the heart as a result of diabetes and a description of the various therapeutic interventions that are available to reverse the effects of diabetes on the heart. Subsequent chapters focus on changes in protein synthesis, membrane function and intermediary metabolism that take place following the onset of diabetes. Since these alterations precede many of the functional and pathological changes, it may be that the processes responsible for the functional decline and tissue injury are initiated by diabetes-induced changes at the cellular and/or biochemical level.

A unique overview of all major angiographic lipid intervention trials, presented by their principal investigators. Basic mechanisms and methodological aspects, including biochemical as well as angiographic aspects, are discussed by experts in these fields. A careful comparison of all available data permits an analysis to be made of what may currently be considered proved, which aspects merit further investigation, and which hypotheses should be rejected. Audience: Clinicians involved in the practice of lipid lowering and investigators involved in lipid-lowering clinical trials. Scientists involved in other areas of lipid research and investigators conducting coronary angiographic trials designed to study the influence of different interventions will find a wealth of information and practical guidelines in this book.

Catheter-delivered therapeutic ultrasound angioplasty is a new technique for use in the treatment of obstructive vascular disease. The treatment differs from balloon angioplasty in that it has been shown experimentally to cause disintegration of calcific and fibrotic atherosclerotic plaques, thrombus dissolution and arterial vasodilation. In contrast to laser technology, ultrasound systems are relatively inexpensive and simple to use and maintain. In the clinical trials detailed in this text, ultrasound angioplasty has been shown to be feasible and safe. Ultrasound Angioplasty is a comprehensive text, addressing the theoretical, experimental and clinical issues. The international contributions reflect the excitement, interest, spirit and cooperation in the research and development of therapeutic ultrasound.

Less than 18 years have passed since the first coronary balloon angioplasty was performed in September 1977 by Andreas Gruntzig. In 1993, 185700 coronary angioplasties were performed in Europe and in many European countries, percutaneous transluminal coronary angioplasty is the most com­ mon method of myocardial revascularization, well ahead of coronary bypass surgery. This explosive growth of interventional cardiology results from major technological advances. The balloons have been markedly improved with a better profile, excellent trackability, and good pushability. The steer­ able guide wires are excellent and can reach the most difficult and the most distal parts of the coronary tree. The guiding catheters offer excellent support and good back-up in the ostium. Meanwhile, new tools have been proposed and designed for a "lesion specific" approach. Coronary stenting which is the "second wind" of angioplasty has dethroned most of the so-called new tools and stents are currently implanted in 30-60% of cases. Similar develop­ ments have occurred in the field of mitral valvuloplasty, ablative techniques in electrophysiology, and in the field of interventions in congenital heart disease. However, these advances would not have been possible without the con­ comitant development of cardiac imaging. For many interventions, cardiac imaging is an necessary pre-requisite: 1. Imaging is mandatory to identify the lesions needing an intervention. Coronary bypass surgery or angioplasty cannot be performed without prior coronary angiography. However, scintigraphic stress testing is also needed to identify perfusion defects in the area supplied by the diseased artery.

Pathophysiology of Heart Failure brings together leading basic scientists and clinicians, presenting new approaches to this complex problem, involving cardiomyopathic processes and ischemia perfusion injury. The result is a synthesis of state-of-the-art information on molecular biology, cellular physiology and structure-function relationships in the cardiovascular system. The role which excess intracellular calcium plays in the genesis of cardiac dysfunction is described as a fundamental mechanism underlying heart failure; one which may lead to improved prevention and treatment. Audience: Clinical and experimental cardiologists will find the book a helpful source of ideas and inspiration.

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.

In 1979 Dr Sperelakis published the `Origin of the Cardiac Resting Potential' in the Handbook of Physiology of the Heart. Since that time, many investigators and teachers of membrane biophysics have used this article as a source of reference on the fundamental principles and equations describing the factors that establish the resting potential in excitable and non-excitable cells. Professor Sperelakis has expanded the scope of this article to provide the present book, creating a comprehensive work and an invaluable reference on the electrophysiological concepts underlying cellular excitability. There has long been a need for a text which precisely defines the assumptions underlying the derivations and equations that describe the principles of electrical excitability and maintenance of ion gradients in excitable cells. Here, Professor Sperelakis not only defines the equations and underlying concepts of membrane potentials, but gives working examples of solutions, thus allowing investigators to utilize the fundamental principles in their research, and students of membrane physiology to establish a sound basis of electrophysiological theory. `I have used the `Origin of the Cardiac Resting Potential' in graduate courses on cell physiology and biophysics, and look forward to using this new book. The time and effort required to put this work together reflects the dedication of Dr Sperelakis to the field of membrane biophysics and electrophysiology in his long, productive career.' From the Foreword by Dr David R. Harder.

Ischemic Preconditioning: The Concept of Endogenous Cardioprotection consolidates, in one volume, both current knowledge and the most recent advances in ischemic preconditioning. The editors have invited investigators at the forefront of ongoing research to provide their scholarly and candid comments concerning each of these issues. This volume includes a comprehensive review of infarct size reduction with ischemic preconditioning, and the most recent data on the effects of preconditioning on ischemia and reperfusion-induced arrhythmias, myocardial metabolism, contractile function, and the coronary vasculature. The role of altered energy metabolism, stress-induced proteins, ATP-sensitive potassium channels, and adenosine -- the major hypotheses that have been proposed to explain the cardioprotective effects of ischemic preconditioning -- are critically reviewed by investigators who have been instrumental in developing these concepts. In addition, the editors raise the intriguing possibility that ischemic preconditioning may be more than simply a laboratory curiosity. Using a multidisciplinary approach, this volume challenges the readers to contribute their own expertise to address the unanswered questions concerning this endogenous, cardioprotective phenomenon.

How to face 'the faces' of cardiac pacing represents an editor's compiled selection of lectures on cardiac pacing and electrophysiology. Electrical stimulation of the heart is an ever-changing and, at times, explosive field. The number of implanting centres is growing tremendously and pacing is not exclusively confined to arrhythmologists. Therefore, the editors attempted to organize a course being both practical in daily clinical management and instructive in understanding technical concepts. The glossary of terms have to be clearly understood before one is able to interpret the complex electrocardiograms of DDD and especially DDDR pacemakers. Those electrocardiograms have to be approached in a system­ atic way, using a step-by-step analysis. The main clinical symptom requiring pacemaker implantation is syncope. It cannot be over-emphasized that syncope is a clinical diagnosis merely based on history and physical examination. The organization of a pacemaker follow-up clinic depends on local facilities and needs. The effectiveness of pacing controls markedly increases when using a systematic approach. Repeated optimal adjustment of pro­ grammable functions is part of the control. Antiarrhythmic drugs are loosing popularity in the treatment of tachy­ arrhythmias. Nonpharmacologic treatment (antitachypacing, implantable defi­ brillators and antiarrhythmic surgery) at the present time have definite indications, probably expanding in the future. When complexity in electronic devices increases, repercussions on ex­ penses, either by the government or social and private insurances, needs consideration.

The Symposium on New Drugs provides a forum for academic investigators, research and development personnel from the pharmaceutical industry and members of the Food and Drug Administration to discuss important clinical research issues. The Ninth Annual symposium on New Drugs addressed the problem of determining the risk versus benefit for use of three important classes of cardiovascular agents: thrombolytic, antiarrhythmic, and hypolipidemic agents. The use of thrombolytic agents has become one of the major advances in clinical intensive cardiologic care in the 1980s. While the lysis of clot(s) obstructing a major coronary artery should reverse or prevent the damage of acute myocardial ischemia and infarction, one must carefully consider the potential risks of such agents in regards to their potential benefits. The time when a thrombolytic agent should be administered to maximize benefit as well as how one defines a dose response relationship using intravenous critical care medicines were discussed as important clinical trial issues. The benefit versus risk data on currently available thrombolytic agents was reviewed and the potential roles for adjunctive agents addressed. Overall strategies regarding post- x thrombolytic care and relationships to sudden cardiac death were also detailed. The panel discussion sections provided a comprehensive view of the current thinking of the various participating groups in this symposium. Sudden cardiac death remains the number one cause of mortality in western industrialized societies.

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.

A critical review of the most up-to-date research on purines and myocardial protection. The role of purines in reversible `myocardial stunning' and irreversible (myocardial infarction) ischemic injury, ventricular arrhythmias, and ischemic preconditioning is discussed in detail, by experts. All reviews address recent and rather controversial issues on purines and myocardial protection. Mechanisms of cardioprotection of exogenous versus endogenous purines are discussed in detail. The contribution of internationally recognized experts in the field of purines and cardiovascular physiology and in myocardial protection makes this a unique and interesting book for clinicians, basic scientists and students.

Autopsy derives from the greek word autopsia, which means act of seeing with one's own eyes. It remains the most objective and accurate method to understand human. disease. Unfortunately, the volume of autopsies in teaching hospitals has decreased dramatically over the past years. The crucial factors that account for this are the recent progress and development of new technologies, especially in diagnostic imaging, immunology, cell biology and genetics. Additionally, the perpetual fear of legal liability by physicians accounts for its further decline. Consequently, physicians and medical students are engaged in fewer autopsies and are not reaping the rich educational rewards that accompany these examinations. The purpose of the autopsy is not only to establish the cause of death, but also to determine the nature and course of the disease process. Our goal with this book is to emphasize the importance of the post-mortem exam and the correlation between pathologic material and clinical data by analyzing actual cases with problem-based methodology. The focus of this handbook is on cardiovascular disease, and when appropriate, other disease categories are included if they have an impact on cardiovascular function. The approach is more than the usual clinico-pathological correlation. Rather, we attempt to present the material from the perspective of the autopsy table. We use the clinical data as the initial framework and the autopsy findings to develop a true understanding of the disease and the associated pathophysiology of the condition.