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Scientific progress with respect to the important role of various lipids in myocardial function and the dearrangements of lipid metabolism underlying ischaemic heart disease(s) has been con­ siderable in recent years. In 1986 alone, an overall number ofl 044 full papers covering the topics'Lipids-Heart-Heart Disease', have been published in a variety of biochemistry, physiology, pharmacology and cardiology journals (source: Index Medicus). They have broadened our in­ sight into the molecular basis of myocardial lipidology and the lipido-chemical basis of car­ diology in health and disease, and have narrowed the gap between promising pharmacological intervention in experimental animals and clinical treatment of patients suffering from an ischaemic heart. Furthermore, they illustrate the fundamental significance of the product of the union between basic and clinical science. The rapid development of knowledge in the'Lipids-Heart-Heart Disease'triad prompted us to organize the International Symposium on Lipid Metabolism in the Normoxic and lschaemic Heart, held in Rotterdam (The Netherlands) on September 22 and 23, 1986. This meeting was a coproject of the Department of Biochemistry I (Medical Faculty, Erasmus University Rotter­ dam) and the Department of Physiology (Medical Faculty, University of Limburg) and was held under the auspices of the GerritJan Mulder Foundation (named after a famous Rotterdam physi­ cian and chemist who lived from 1802-1880) whom we thank for their co-operation. The present volume is a compendium of invited papers and contributions selected from the posters presented during the symposium.

Physiologists have long been interested in the interaction, or coupling, between the heart and the vasculature. The early literature consists mainly of phenomenological descriptions of cardiac alterations resulting from specific interventions in the vasculature. Hundreds of studies, for example, describe functional aspects of hypertrophied myocardium associated with the excessive vascular loading produced by various types of experimental hypertension. Recently, the concepts of ventricular/vascular interaction have found important clinical application. The widespread use of vaso­ dilators and of intraaortic counterpUlsation balloons for unloading an ov­ erburdened, diseased heart is a prime example. Despite the interest in this field, until as recently as 20 years ago we were not able to describe ventricular or vascular function in a framework suitable for quantitatively expressing the interaction between these two complex systems. Three major developments-description of ventricular function in terms of both the time-varying elastance and the pump function graph and quantification of vascular function in terms of impedance­ have changed this. These functional descriptions now enable systems en­ gineers, bioengineers, physiologists, and clinicians to address very specific quantitative aspects of ventricular/vascular interaction and have resulted in a flurry of papers and symposia devoted to this subject.

The International Hypoxia Symposium convenes biannually to bring together international experts from many fields to explore the state of the art in normal and pathophysiological responses to hypoxia. Representatives from five continents and 32 countries joined together in February 2003 for four days in the dramatic mountains of Banff, Alberta. As editors of the Proceedings of the International Hypoxia Symposia, we strive to maintain a 26 six year tradition of presenting a stimulating blend of clinical and basic science papers focused on hypoxia. Topics covered in 2003 include hibernation and hypoxia, hypoxia and fetal development and new advances in high altitude pathophysiology, oxidative stress and membrane damage, hypoxic regulation of blood flow, heat shock proteins in hypoxia, and future directions in hypoxia research. In 2003 we also had the privilege ofhonoring John W. Severinghaus as a friend, colleague, mentor and inspiration to many in the field. Tom Hornbein's personal tribute to John Severinghaus is the first chapter in this volume, followed by an entertaining update of the history of the discovery of oxygen written by John Severinghaus.

Coronary heart disease is one of the major health problems in indus­ trialized nations because of its high incidence and severity. Recent innovations in medical and surgical treatment of coronary heart dis­ ease have increased the importance of accurate diagnostic methods for determining the severity of coronary disease, identifying potential treatment alternatives, and evaluating the results of treatment. Great advances have also been made in basic research on coronary circula­ tion and its interaction with myocardial contraction and relaxation and neural and humoral control. With respect to these developments, the papers included in the present monograph deal with important topics concerned with the basic mechanism of coronary circulation as well as ones of clinical relevance. It is directed toward physicians (cardiologists, cardiac surgeons, cardiac radiologists, anestheologists, and others) and basic scientists (e.g., physiologists, bioengineers). We would like to em­ phasize the importance of a multidisciplinary approach in which basic scientists and clinicians work closely together. This volume consists of nine chapters. Chapter 1 contains macro­ scopic and microscopic descriptions of coronary vascular anatomy, which is closely related to the functions of coronary circulation. In Chap. 2 two methods in current use to evaluate phasic coronary blood velocity waveforms are presented, i.e., the laser Doppler and ultrasound Doppler methods. Chapter 3 describes the mechanical properties of coronary circulation, a knowledge of which is indispens­ able for an understanding of coronary arterial and venous blood flow velocity waveforms in relation to cardiac contraction and relaxation.

This book covers the latest information on the anatomic features, underlying physiologic mechanisms, and treatments for diseases of the heart. Key chapters address preclinical animal models for cardiac research and clinical trials performed, cardiac mapping systems, heart-valve therapies and other device-based tools and technologies for cardiac diagnoses and treatments. Once again, companion of supplementary videos offer unique insights into the device-tissue interfaces, including those within beating hearts: i.e., these supplemental videos enhance ones understandings of key points within the text. The “Handbook of Cardiac Anatomy, Physiology and Devices”, the Fourth Edition is a comprehensive and state-of-the art resource textbook that should provide clinicians and biomedical engineers alike, with the authoritative information and background they need to work on and implement tomorrow's generation of life-saving cardiac therapies and devices.

Dieses Buch versteht sich als ein umfassender Leitfaden für Sport- und Gesundheitsexpert•innen, Studierende, Wissenschaftler•innen, Trainer•innen, Athlet•innen verschiedener Sportarten und für alle, die ein allgemeines Interesse an gleichzeitigem Ausdauer- und Krafttraining haben. Nach einem kurzen historischen Überblick über die wissenschaftlichen Fortschritte zum kombinierten Ausdauer- und Krafttraining über die letzten Jahrzehnte werden in Abschnitt 1 die epigenetischen sowie physiologischen und neuromuskulären Unterschiede von Ausdauer- und Krafttraining erörtert. Anschließend wird in Abschnitt 2 eine aktuelle Analyse der bestehenden Erklärungsansätze für das Interferenzphänomen vorgenommen, während in Abschnitt 3 die trainingsmethodischen Besonderheiten des kombinierten Ausdauer- und Krafttrainings erläutert werden. In den Abschnitten 4 und 5 werden die theoretischen Überlegungen aus den vorangegangenen Abschnitten im Anschluss praktisch auf verschiedenste Zielgruppen angewandt, von Kindern und älteren Menschen bis hin zu Sportlern verschiedener Sportarten. Kombiniertes Ausdauer- und Krafttraining: Wissenschaftliche Grundlagen und Ableitungen für die Trainingspraxis ist ein neuartiges Buch zu einem der umstrittensten Themen der Sport- und Trainingswissenschaft. Oberstes Ziel der Herausgeber ist es, dieses Buch zu einem leicht verständlichen und gleichzeitig wissenschaftlich fundierten Leitfaden für die tägliche Praxis zu machen.

This volume of the series Cardiac and Vascular Biology presents the most relevant aspects of vascular mechanobiology along with many more facets of this fascinating, timely and clinically highly relevant field. Mechanotransduction, mechanosensing, fluid shear stress, hameodynamics and cell fate, are just a few topics to name. All important aspects of vascular mechanobiology in health and disease are reviewed by some of the top experts in the field. This volume, together with a second title on cardiac mechanobiology featured in this series, will be of high relevance to scientists and clinical researchers in the area of vascular biology, cardiology and biomedical engineering.

This ambitious and comprehensive handbook represents an essential contribution to our current understanding of interactions between heart and brain, a research topic generating growing interest. Despite the increasing awareness that neural mechanisms are the primary cause of cardiac disease and its progression, therapy continues to focus on end-organ protection and does not approach the neural core of the problem. Growing public health problems such as heart failure are still treated with autonomic drugs that are 30-40 years old and simply act on cardiac receptors. However, it has now been shown that the progression of ischemic heart disease to heart failure is mainly due to abnormal central responses to incipient cardiac disease, with neural activation the primary cause rather than the consequence of cardiac remodeling. Written by leading international experts in their respective research areas, the book presents a variety of perspectives on the coretopic: from social and philosophical to gender-related aspects.It is designed for a broad readership and includes dedicated sections for cardiologists, psychiatrists, neurologists and psychotherapists looking for a more insightful and targeted approach to neuro-cardiovascular disease.

This textbook focuses on the vascular biology and physiology that underlie vascular disorders in clinical medicine. Vascular biomedicine is a rapidly growing field as new molecular mechanisms of vascular health and disease are unraveled. Many of the major cardiovascular diseases including coronary artery disease, heart failure, stroke and vascular dementia are diseases of the vasculature. In addition vascular injury underpins conditions like kidney failure and cardiovascular complications of diabetes. This field is truly multidisciplinary involving scientists in many domains such as molecular and vascular biology, cardiovascular physiology and pharmacology and immunology and inflammation. Clinically, specialists across multiple disciplines are involved in the management of patients with vascular disorders, including cardiologists, nephrologists, endocrinologists, neurologists and vascular surgeons. This book covers a wide range of topics and provides an overview of the discipline of vascular biomedicine without aiming at in-depth reviews, but rather offering up-to-date knowledge organized in concise and structured chapters, with key points and pertinent references. The structure of the content provides an integrative and translational approach from basic science (e.g. stem cells) to clinical medicine (e.g. cardiovascular disease). The content of this book is targeted to those who are new in the field of vascular biology and vascular medicine and is ideal for medical students, graduate and postgraduate students, clinical fellows and academic clinicians with an interest in the vascular biology and physiology of cardiovascular disease and related pathologies.

This book describes the field of osteocardiology, an exciting and new sub-discipline within cardiovascular science, which will become the cornerstone for defining the timing and treatment of cardiovascular calcification in the future. With the advent of large cohort databases and experimental mechanistic studies, research has elucidated evidence confirming that traditional cardiovascular risk factors are responsible for the development of atherosclerotic calcification and identified the critical elements of atherosclerosis, including foam cell formation, vascular smooth muscle cell proliferation and extracellular matrix synthesis, which over time forms bone in the heart.Osteocardiology: Cardiac Bone Formation is a practical overview of bone formation in the heart and is destined to become the cornerstone for education of medical students, residents, fellows, graduate students, physician scientists and scientists, for future research and ongoing development in medical therapies to slow or halt the progression of bone formation in the heart.

This book covers the latest developments in the therapeutic implications of angiogenesis, ranging from angiogenesis in the brain, angiogenesis in cancer, angiogenesis'role in atherosclerosis and heart disease as well as metabolic disorders and peripheral vascular disease. The book is comprehensive in its coverage of angiogenesis in a diverse set of diseases and examines the role of cellular and subcellular structures during the development of angiogenesis. Well-organized and thorough, this is an ideal book for researchers and biomedical engineers working in the field of therapeutic implications of angiogenesis.This book also:Covers the basics of the physiology of angiogenesis, including VEGF pathways in angiogenesis, integrins in angiogenesis, angiogenesis and exercise physiology, and moreDetails the role of angiogenesis in atherosclerosis and heart disease, including vascular endothelial growth factor and atherosclerotic plaque progression as well as angiogenesis and heart failure Illustrates in detail brain angiogenesis after stroke and the relationship between angiogenesis and Alzheimer's disease

This book covers the latest information on the anatomic features, underlying physiologic mechanisms, and treatments for diseases of the heart. Key chapters address animal models for cardiac research, cardiac mapping systems, heart-valve disease and genomics-based tools and technology. Once again, a companion of supplementary videos offer unique insights into the working heart that enhance the understanding of key points within the text. Comprehensive and state-of-the art, the Handbook of Cardiac Anatomy, Physiology and Devices, Third Edition provides clinicians and biomedical engineers alike with the authoritative information and background they need to work on and implement tomorrow's generation of life-saving cardiac devices.

Inotropic stimulation of the myocardium, as well as vasodilation and diuresis as essential principles in the treatment of congestive heart failure have recently met with considerable criticism and reevaluation. It is generally agreed that unloading of the heart, either through vasodilation and/or diuresis, improves the working conditions of the dilated, failing heart. It reduces myocar­ dial oxygen consumption through reduction of chamber radius and, thereby, wall tension as the major determinants of myocardial oxygen consumption. Inotropic stimulation, quite in contrast, does not conserve oxygen. It rather consumes energy and that may be disadvantageous in situations of compromised oxygen supply and energy metabolism of the working myocardium. However, under conditions of suf­ ficient oxygen supply and metabolic support inotropic stimulation may bring about in­ creased pumping and subsequent improvement of myocardial failure. In recent years it could convincingly be demonstrated that vasodilation leads to symp­ tomatic improvement of congestive heart failure, improvement of exercise tolerance, and it prolongs life - especially in the case of ACE-inhibitors and the combination of hydra­ lazine with long-acting nitrates. Quite in contrast, equally beneficial effects could not be demonstrated for inotropic agents in congestive heart failure. Only for the cardiac glyco­ sides has it been shown that beneficial effects can be achieved, especially if atrial fibril­ lation with absolute arrhythmia is present. The influence of the cardiac glycosides on the latter represents an effect which is independent of the inotropic action.

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.

Cardiovascular fluid mechanics is now used as a tool in determining diagnosis, treatment, and prognosis by physicians and surgeons working in the fields of cardiology and angiology. The text is based on a considerable amount of clinical and experimental data on blood flow in the heart and large vessels obtained using various methods such as ultrasound pulsed Doppler velocimetry (including Doppler color flow imaging), catheter-tip electromagnetic velocimetry, hot-film anemometry, and laser Doppler velocimetry. The book will introduce medical researchers and clinicians to this rapidly developing field and allow them to apply the knowledge and the methods of fluid mechanics to practical medicine.

Assessment of cardiac energetics at the level of ATP-synthesis, chemomechanical energy transformation and whole organ dynamics as a function of haemodynamic load, ventricular configuration and oxygen- and substrates supply is basic to understanding cardiac function under physiological and pathophysiological (hypertrophy, hypoxia, ischaemia and heart failure) conditions. Moreover, cardiac energetics should be an important consideration in the choice and application of drugs especially in the case of vasodilators, inotropic agents and in cardioprotective measures. Only by considering energetics at the subcellular, cellular, and whole-heart level we can arrive at a better understanding of cardiac performance and ultimately better clinical judgement and drug therapy. Quantification of myocardial energetics will also help to determine the optimal time for surgical interventions such as valvular replacement or aneurysm resection. The present volume is the outcome of an international symposium on cardiac energetics held in Gargellen/Montafon (Austria), June 1986. The contributions will certainly help bridge the existing gap between basic research involving isolated structures and that involving the whole organ, on the one hand, and render the results derived from basic research applicable to clinical problems, on the other hand.

Dieser Buchtitel ist Teil des Digitalisierungsprojekts Springer Book Archives mit Publikationen, die seit den Anfängen des Verlags von 1842 erschienen sind. Der Verlag stellt mit diesem Archiv Quellen für die historische wie auch die disziplingeschichtliche Forschung zur Verfügung, die jeweils im historischen Kontext betrachtet werden müssen. Dieser Titel erschien in der Zeit vor 1945 und wird daher in seiner zeittypischen politisch-ideologischen Ausrichtung vom Verlag nicht beworben.

This new edition of Essential Cardiac Electrophysiology: The Self-Assessment Approach continues the successful formula of the first edition, providing a concise and thorough overview of Electrophysiology supplemented by challenging questions readers can use to test their knowledge and prepare for examinations. Comprehensively updated and significantly expanded to include the latest recommendations, findings from leading-edge research, emergent diagnostic tools, and new therapeutic options, Essential Cardiac Electrophysiology: The Self-Assessment Approach now offers coverage of some o.

This book summarizes present knowledge of different mechanisms involved in the development of positive and negative consequences of cardiac adaptation. Particular attention is paid to the still underestimated adaptive cardiac responses during development, to adaptation to the frequently occurring pressure and volume overload as well as to cardiac changes, induced by enduring exercise and chronic hypoxia. Cardiac Adaptations will be of great value to cardiovascular investigators, who will find this book highly useful in their cardiovascular studies for finding solutions in diverse pathological conditions; it will also appeal to students, fellows, scientists, and clinicians interested in cardiovascular abnormalities.

Taurine 8 represents the combined efforts of investigators on the roles of the amino acid taurine on human health and disease. The chapters covered in this book are directly derived from presentations of the contributors at the 18th International Taurine Meeting held in Marrakech, Morocco in April 2012. The purpose of this book is to disseminate current findings on taurine's contribution in several organ systems. This book covers the following topics: Taurine in the Nervous System, Taurine in the Immune System, Taurine and Diabetes, and Taurine and the Cardiovascular System. Dr. Abdeslem El Idrissi, College of Staten Island and Dr. William L'Amoreaux, College of Staten Island, were co-chairs of the Organizing Committee for the meeting. Data presented at this meeting provided compelling evidence that taurine is not only cytoprotective in cardiomyocytes, but also is a potent GABA agonist, whereby it can facilitate vasodilation of conducting arteries. Taurine conjugates, such as taurine chloramine, may protect cells from oxidative stress via increased HO-1 expression. In adult rodents, taurine has a potent effect on plasma glucose levels, likely through the release of insulin in pancreatic beta cells. As a potential neurotransmitter, taurine is known to work via the GABAergic system, but current research presented at this meeting suggest that taurine may interact with glutamate and serotonin receptors as well. Data are also presented to demonstrate the protective roles of taurine on neurons in neuroblastoma. Perhaps the most important and exciting presentation is the role of taurine and alcohol: the combination may be lethal. Data are also presented at this meeting of the potential role taurine may have as an adjuvant treatment with cisplatin in chemotherapy.

Dieser Band gibt einen Überblick über aktuelle Aspekte der koronaren Herzkrankheit, von der heute nahezu jeder 2. Bundesbürger betroffen ist. Namhafte Experten diskutieren die Bewertung von Risikofaktoren und Perspektiven der primären und sekundären Prävention, die Rolle von Endothel und Thrombozyten und die sich daraus ergebenden therapeutischen Implikationen bei stabiler und instabiler Angina pectoris. Das Problem der asymptomatischen Myokardischämie und ihrer Behandlung, die Möglichkeiten und Grenzen der Pharmakotherapie, die gegenwärtigen Konzepte zur Behandlung des akuten Myokardinfarktes sowie der Stellenwert der PTCA und neuerer Entwicklungen wie die Laser-Angioplastie werden dargestellt. Hervorzuheben sind die angioskopischen Aufnahmen, die den Blick in das Innere von arteriosklerotisch veränderten Herzkranzgefäßen erlauben. Damit gibt dieses Buch wertvolle Informationen für die ärztliche Tätigkeit bei der Therapie der koronaren Herzkrankheit.

Hopes to develop apolipoproteins for diagnostic or, even better, therapeuticpurposes are growing. Areas of use may range from arterial disease to AIDS, fertilization programs, neurological or inflammatory disorders, and the like. However, these young members of the large family of circulating proteins still deserve careful study, both in terms of structural and functional properties and of their pathological changes. In addition, related molecules, in particular belonging to the family of enzymes, such as lipases and acyltransferases, offer exciting insight into the mechanisms of regulation of lipid transport and exchange. Described hereis the use of apolipoproteins and enzymes in the diagnosis of coronary and cerebrovascular disease. Structural and functional changes of apolipoproteins are related to lipid transport and binding to different receptors. Further, the development of apolipoprotein drugs and their possible clinical use for vascular and non vascular disease is discussed and finally an overview on lipoprotein transformation processes, expression systems and natural mutants is provided.

An up-to-date overview of blood coagulation, hemostatis, and thrombosis, this volume also provides a state-of-the-art report of current anti-thrombotic and anti-coagulant strategies as well as a summary of current research interest in the area and potential future targets. It attempts to balance traditional pharmacology with the newer sciences of molecular biology and in so doing, sets a framework for future advances in the field. The book is a concise, current and useful reference for the basic researcher as well as the practicing physician working in the fields of cardiology, internal medicine or surgery.

The development of a new antiarrhythmic drug involves many people with disparate skills. The organic chemist who makes it is guided not only by the structure-action relations of previous compounds, but by anticipation of a requirement for a particular type of action. In fact several of the best-known antiarrhythmics, including lidocaine, mexiletine, amiodarone and verapamil, were originally synthesized for other purposes. Physicians have to determine whether the new drug works, and pharma­ cologists how it works. For some years I have believed that there was room for a work which could be understood by all these groups and which could enlighten each about the point of view of the others. Thus when I was invited by Springer-Verlag to prepare a volume in their series Handbook of Experimental Pharmacology, I already had a firm conception of what its form should be. In any multi-author work there are two objectives which cannot always readily be reconciled. The first is to select topics which would relate to each other in a coherent manner. to give a logical and orderly shape to the volume as a whole. The second is to offer authors the greatest possible freedom to express themselves as they wish. When the general design was complete, prospective contributors were invited to write specific chapters, being provided with a complete list of their coauthors and chosen topics, so that they could avoid overlap.

H. RoSKAMM This International Symposium to be held on the occasion of the third anniversary of our institution and under the auspices of the European Society of Cardiology is entitled'Ventricular Function at Rest and During Exercise'. We have chosen the general term'ventricular function', because we want to include the different aspects of myocardial function like contrac­ tility, relaxation and compliance and their influence upon the overall pumping function of the heart. Heart failure at rest is a rather advanced outcome of a continuous spectrum of function disturbances. In order to grade these, it is reasonable to differentiate between pump function of the heart as a whole and muscle function of the myocardium. Compen­ satory factors like hypertrophy or the Frank-Starling mechanism may maintain the overall pump function of the ventricle, despite a defect in the underlying myocardial contractility. The time sequence of the func­ tional disturbances may be as follows (Fig. 1): EXERCISE £''-----,--------------, >-'5 ~, ~ ~, ~'~ I o u f--~__;_;IJ'_'_~''''• t REST II Fig. 1. Schematic presen­ REDUCTION OF CON REDUCTION OF CON PUMP FAILURE tation of time sequence of TRACTILITY RESERVE TRACTllITY. or REST progression in deteriortation _ TIME of ventricular function xvn The lower line represents contractility at rest, the upper one contrac­ tility during maximum exercise; the range between these two lines can be called contractility reserve.

The sodium of animal cell membranes converts the chemical energy obtained from the hydrolysis of adenosine 5'-triphosphate into a movement of the cations Na + and K + against an electrochemical gradient. The gradient is used subse­ quently as an energy source to drive the uptake of metabolic substrates in polar epithelial cells and to use it for purposes of communications in excitable cells. The biological importance of the sodium pump is evident from the fact that be­ tween 20-70% of the cell's metabolic energy is consumed for the pumping pro­ cess. Moreover, the sodium pump is an important biological system involved in regulatory processes like the maintenance of the cells'and organism's water me­ tabolism. It is therefore understandable that special cellular demands are han­ dled better by special isoforms of the sodium pump, that the expression of the sodium pump and their isoforms is regulated by hormones as is the activity of the sodium pump via hormone-regulated protein kinases. Additionally, the sodium pump itself seems to be a receptor for a putative new group of hormones, the endogenous digitalis-like substances, which still have to be defined in most cases in their structure. This group of substances has its chemically well known coun­ terpart in steroids from plant and toad origin which are generally known as'car­ diac glycosides'. They are in medical use since at least 200 years in medicine in the treatment of heart diseases.

Traditionally, cardiac hypertrophy is regarded as an adaptation of the heart to permanent mechanical overload. Regardless of the fact that many different and often unknown primary causes can result in heart failure, mechanical overload and myocardial hypertrophy is found in almost all forms of manifest chronic heart failure (apart from failure due to extramyocardial hindrances to inflow or to relaxation). However, the reactive enlargement of myocardial mass in response to an enhanced hemodynamic burden appears to be a double-edged sword. Obviously, the hypertrophy helps to reduce the enhanced ventricular wall stress in heart failure by adding contractile units to the overdistended chamber wall. However, in recent years it became clear that this adaptive hypertrophic process is rather complex and may include problematic facets. The adaptive hypertrophy includes proliferation of the nonmyocyte cardiac cells as well as substantial alterations in the phenotype of the growing myocytes due to differential changes in gene expression.

The myocardium in heart failure: Cellular and subcellular alterations in the failing human myocardium. H. Just Medizinische Universitatsklinik Freiburg i. Br., Innere Medizin III - Kardiologie, FRG The syndrome of heart failure continues to be a major challenge to clinicians and scientists. Incidence and mortality of the disease are high, the patient is disabled, and is permanently threatened by the high morbidity and mortality. The clinician faces a syndrome of complex pathophysiology. Multiple causes or underlying disorders of the heart have to be differentiated from heart failure itself, which often results in exceedingly difficult diagnoses. Likewise, prognostication meets with difficulties due to problems in separating influences of the underlying disease and the heart failure syndrome itself. In chronic refractory failure annual mortality may exceed 50%. If aortic stenosis or ischemic cardiomyopathy with main­ stem lesions are present, this percentage may be even higher. The situation becomes particularly threatening to the patient when the reduction in cardiac performance goes along with complex ventricular arrhythmias. Therapy has remained difficult and of limited effectiveness. Major progress was achieved with the introduction of diuretic substances. Of similar importance was the introduction of va so dilating drugs into the treatment of heart failure. The principle of vasodilation has greatly improved our understanding of the disease, and has brought about a major improvement of symptoms, increase of exercise capacity, and reduc­ tion of mortality. This is especially true for the introduction of the angiotensin converting enzyme inhibitors.

In recent years, we have witnessed a rapid expansion of our knowledge regarding the role of the endothelium in the control of vascular tone (and organ perfusion) in health and disease. Physiology, pharmacology, and molecular biology have uncovered a wealth of information on structure and function of this heretofore largely neglected'organ'. Clinical medicine is now called upon to define the clinical significance of these observa­ tions that imply the mechanisms of blood coagulation, e.g., the interaction of throm­ bocytes with the endothelium, vasomotor control, and specifically, the regulation of smooth muscle tone with consequences for vascular resistance and conductance and organ blood flow. Finally, metabolism of lipids with the everlasting problem of athero­ sclerosis is an important aspect. In a second step, implications regarding the improvement of current therapeutic con­ cepts, as well as the development of new modalities of pharmacotherapy will have to be discussed. The topic addressed by the 1990 Gargellen Conference: Endothelial Mechanisms of Vasomotor Control, clearly is of interest for both basic scientists and clinicians. It has been the aim of the organizers, the Society for Cooperation in Medical Science (SCMS) with this and the previous symposia to foster and support both basic science and clinical research. Research in medicine today shows two major directions of development: on the one hand, increasing involvement of the basic sciences and their methodology. On the other hand, statistical validation of concepts and therapeutic strategies in large scale population-and multicenter-studies.

R. Droh Ladies and gentlemen. dear friends and colleagues. we welcome you very cordially to our symposium'Innovations in Management and Technic and Pharmacol­ ogy'. We are very glad that you have come to Liidenscheid and we do hope that our programme will fulfil your expectations. We decided to hold this symposium, because it is getting more and more dif­ ficult to select innovations at international congresses around the world which are important for our clinical work. Now and in the future our intention is to present the actual state of technology. management and pharmacology. We would be very glad to receive your suggestions for further symposia. The industry has the same problems as we have. They do not only have to search for those things which can be realized and which are desirable, but also for those things which can be sold. But the industry must also be stimulated by the inventors and by the users, so we want to bring together the industry, the physicians and the inventors for fruitful discussions. And we hope that in the fu­ ture the industry will provide us more quickly with those technical and organiz­ ational aids that we need. We want the indu~try no longer running behind the market but heading the market. At present too many interesting developments are killed by so-called market analysis, in the beliefing that such analysis can always prove what cannot be sold. In anaesthesia many companies are always busy with the same product.

Cardiovascular dynamics is a field in which modelling and systems analysis have formed an extremely important discipline. For example, understanding of even such a fundamental function of the circulation as the relationship between central venous pressure apd cardiac output has required evolution of a pertinent model based on years of exhaustive ex­ perimental investigations by Starling, Starr, and Guyton. Hemodynamic analyses of pulsatile pressures and flows in the arteries and veins have been a continuing challenge taken up by champions of fluid dynamics such as Frank, Wetterer, Taylor, and Wormersley, just to mention a few names, and some kind of model was always proposed as a conceptual framework. An even greater challenge to cardiovascular dynamicists was how to analyze the intermittent coupling of the ventricle and the arterial or venous vasculature through the valve. The availability of numerical solutions by computer and the recently evolved ventricular model with a time-varying elastance and a pressure-dependent internal resistance opened the way to analysis of this coupling. The ever­ increasing speed of computers has also facilitated trips between the fre­ quency and the time domain, even on-line for some experimental studies. This book contains many analyses dedicated to the interactions between the heart and the vasculature, providing the reader with findings at the cutting edge of current research in this field.

Major epidemiologists from the UK, USA and Europe contribute to the first ever, much needed comprehensive review of the epidemiology of peripheral vascular disease in the lower limbs.

The objective of this book is to provide the researcher and clinician with the recent developments in the analysis and assessment of cardiovascular func­ tion. The chapters are organized into sections that correspond with the various anatomical levels of the cardiovascular system. To a large extent, recent focus on the cardiovascular system function has been directed at the molecular level to the near exclusion of the tissue and organ function. While this may be useful in developing new therapeutic drugs, it does not aid the cardiologist or surgeon, who routinely deal with patient symptoms. This book integrates the micro-level and organ-level function so that new infor­ mation may be assimilated into the cardiovascular system as a whole. Within each section, the chapters have been arranged to progress from recent theoretical developments, to experimental research, and finally to clinical applications. This approach facilitates the timely transfer of infor­ mation from basic research to the clinic. The strength of the analytical approach will be evident to the reader. The theoretical analysis offers guidance to experimental design and, in some cases, offers solutions where measurements are as yet unattainable. In moving from newly attained knowledge to clinical practice, this book emphasizes the noninvasive meth­ in the future as technological advances ods. Such methods are desirable occur and the trend towards early preventive diagnosis is sought. What follows are highlights of new developments covered in each section of the book.

'What we call the beginning is often the end, and to make an end is to make a beginning. The end is where we start from.'T. S. ELIOT,'Geroniton'The discovery of endothelin-l was both an end and a beginning. It is an end because this discovery has started a plethora of investigations as to endothe1in's sites of production, mode of action, it's normal and abnormal physiological role and its involvement in a variety of pathological conditions ranging from renal failure to myocardial infarction, cardiac hypertrophy, hyperten­ sion, cyclosporine induced toxicity, mental depression, renal failure, stress related illness, and even stroke and sudden death. It is a beginning because no one can foresee where the investigations will ultimately lead, or how they will end. The discovery of the endothelins was a very recent event and soon specialist books will start to appear dealing in detail with different aspects of their chemistry, physiological role and pathological importance. The present book is intended to act as a guide and primer for those who are becoming intrigued by the many endothelin­ related articles which are now appearing in the journals but who as yet have not had the time or opportunity to be caught up in the web of enthusiasm and excitement which is motivating those more directly involved in the field of research.

'Function dictates structure'is a classic paradigm reaffirmed in Wolff's law of the skeletal system. A major question being addressed by current research in biomechanics is whether this doctrine also holds true for the cardiovascular system and connective tissues. Taking a multidisciplinary approach to this question has produced new insights into the sensors, signals, and activators that produce remodeling and functional adaptation in cardiac muscle, blood vessels, and bone, including important new findings on the response of vascular endothelial cells to shear stress. Other work focuses on the extent of remodeling and adaptation processes in tendons, ligaments, and intervertebral discs. Together with two companion volumes, Computational Biomechanics and the Data Book on Mechanical Properties of Living Cells, Tissues, and Organs, this monograph will prove invaluable to those working in fields ranging from medical science and clinical medicine to biomedical engineering and applied mechanics.

Several methods have been used to demonstrate the vasculature of different organs in man and other species. Many attempts to evaluate the precise microangioarchitecture of organ systems remained unproductive, others were controversial. The development of electron microscope in thirties opend new perspectives in researching microvascular systems. Transmission electron microscopy provided a two-dimensional view on microcirculatory system at higher magnifications, however, its standardization was delayed unnecessarily. The use of methyl methacrylate and related compounds for obtaining replicas of vascular beds, and their study in scanning electron microscope opened a new window in micromorphological research. For the first time, a three-dimensional image analysis of the vascular system was possible. The microvascular corrosion casting method has meanwhile attracted the interest of many contemporary scientists. Its application to medical and biological problems justify it to be used as a routine method for microvascular investigations. The first investigators who used this method, focused either on methodological details or they dealt with the normal microanatomy of organs. The advantages of this method in demonstrating pathological microvascular patterns are also evident.

A vast literature has been concerned with arteriosclerosis and yet, many aspects of pathogenesis and of the mechanism of development of the arteriosclerotic vascular lesion remain only poorly understood. In recent years, our knowledge of the earliest stages of arteriosclerosis have greatly improved. By now, we have learned to relate morphologic changes to disturbances in function. It has been of particular impor­ tance that components of the arterial wall could be analyzed in regard to dysfunction, for example, in the endothelium or the vascular smooth muscle. The interaction of the different morphological components of the vascular wall could thus be much bet­ ter understood. Likewise, the interaction between the arterial wall and the flowing blood could be much better described, including the intimate relationship between platelets and the endothelium, the coagulation system and the endothelium, the granulocytes and the endothelial cell layer, as well as processes of migration of blood cells into the subendothelial space. The recognition of functional and morphological disturbance has attained clinical significance not only because the arteriosclerotic diseases have quantitatively reached the dimensions of an epidemic, that is, of a magnitude never been witnessed. It is also because of the development of new drugs that interfere with the atherogenic process and thereby prevent the development of the disease or halt its progression. It is also becoming increasingly possible to inhibit the occurrence of complications in existing arteriosclerotic lesions in manifest disease, i. e.