Basic Science for the Cardiologist – serie

Hemodynamics makes it possible to characterize in a quantitative way, the function of the heart and arterial system, thereby producing information about what genetic and molecular processes are of importance for cardiovascular function.Snapshots of Hemodynamics: An Aid for Clinical Research and Graduate Education by Nico Westerhof, Nikos Stergiopulos and Mark I. M. Noble is a quick reference guide designed to help basic and clinical researchers as well as graduate students to understand hemodynamics. The layout of the book provides short and independent chapters that provide teaching diagrams as well as clear descriptions of the essentials of basic and applied principles of hemodynamics. References are provided at the end of each chapter for further reading and reference.Nico Westerhof, PhD is affiliated with the Laboratory for Physiology at VU University Medical Center in Amsterdam, The Netherlands.Nikos Stergiopulos, PhD is affiliated with the Laboratory of Hemodynamics and Cardiovascular Technology at the Swiss Federal Institute of Technology in Lausanne, Switzerland.Mark IM Noble, DSc, MD, PhD is affiliated with Cardiovascular Medicine at Aberdeen University, Aberdeen Royal Infirmary in Aberdeen, Scotland.

Adrenomedullin was discovered in 1993 in an extract of human pheochromocytoma while monitoring cAMP levels in rat platelets. Adrenomedullin has attracted considerable interest among cardiologists due to its impact on the cardiovascular system which includes a decrease in blood pressure in vivo; an impact on vascular smooth muscle cells; increases cAMP levels; indirectly reduces blood pressure and has role in the pathogenesis of arteriosclerosis.Adrenomedullin in Cardiovascular Disease is an up-to-date review of the most relevant aspects of adrenomedullin. It encompasses a broad range of fields including biochemistry, molecular biology, physiology, pharmacology, pathophysiology of cardiovascular disease and clinical applications of adrenomedullin to cardiovascular disease.

Effective new treatments of heart disease are based on a refined understanding of cellular function and the heart's response to environmental stresses. Not surprisingly therefore, the field of experimental cardiology has experienced a phase of rapid expo­ nential growth during the last decade. The acquisition of new knowledge has been so fast that textbooks of cardiology or textbooks of cardiovascular physiology are often hard-pressed to keep up with the most important conceptual advances. Witness the explosive increase in knowledge about signaling pathways of cardiac growth, transcrip­ tional regulation of cardiac metabolism, hormonal signaling, and the complex responses of the heart to ischemia, reperfusion, or ischemic preconditioning. This book is meant to bridge the gap between original literature and textbook reviews. It brings together inves­ tigators of various backgrounds who share their expertise in the biology of myocardial ischemia. Each chapter is a self-contained mini-review, but it will soon become apparent to the reader that there is also a common thread: Molecular and cellular cardiology has never been more exciting than now, but ever more exciting times are yet to come. The Editors ACKNOWLEDGEMENTS - Publication of this book was generously supported by Sanofi-Aventis Hellas. - Eikon creative team provided the technical assistance in preparing the manuscripts. - We thank Dr. Bernard Swynghedauw for all his scientific support.

Profound mortality rates, due to cardiovascular disease, are a worldwide problem. One of the consequences from complications of this silent and chronic arterial disease is atherosclerosis. The challenge for the practitioner is adapting diagnostic and therapeutic responses to prevent this common and complex disease. Dyslipidemia, disorders of the metabolism of soluble transporter of lipids in extracellular spaces of the human body (including blood), called lipoproteins, are major cardiovascular risk factors and are themselves multifactorial diseases, resulting from interactions between genetic and environmental factors. The study of genetic factors has recently taken a new path with the study of DNA as an experimental object. More than 50 genes of lipoprotein metabolism have been identified in both their physiological actions and their contribution to the pathogenesis of human dyslipidemia. The diversity of these observations has refined our knowledge of the control of lipid metabolism and energy homeostasis in living organisms beyond the limits of the cardiovascular system.These studies have given way to a shake-up of former phenotypic classifications, distinguishing new entities, defining targeted therapeutic strategies, providing a basis for different patterns of disease distribution in human populations. The book is a fitting addition to the Endocrine Updates series. The aim of these publications is to provide the clinician with cutting edge, yet succinct, access to the latest advances in endocrinology.

What is the role of potassium in preventive cardiovascular medicine? Information related to this question has accumulated for nearly 100 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.

Cardiac Cellular Electrophysiology is for the clinical cardiologist who wishes to refresh or deepen his understanding of the cellular basis of cardiac electrophysiology, and to those researchers interested in the basis of the electrical activity of the heart: researchers, pharmacologists, teachers in physiology, pharmacology and other biomedical studies, and medical students from graduate to postgraduate level. This book is a primer of basic electrophysiology, the cardiac action potential, and the physiological basis of the electrocardiogram. The authors provide the necessary background in cellular electrophysiology to allow accessibility of this material to a wide audience. Edward Carmeliet and Johan Vereecke, Katholieke University Leuven, Belgium, have collaborated for over 30 years in cardiac electrophysiology research. Their studies include the genesis of the normal action potential, its changes in ischaemia, the effect of drugs, and the mechanism of arrhythmias, using techniques from the classic potential registration with intracellular microelectrodes to whole cell clamp and single channel measurements.

The classical physiological studies on the cardiovascular system have improved our knowledge on the function of this system under normal and pathological conditions. This knowledge was the basis of the breakthrough for diagnostic techniques like the Swan-Ganz catheter, coronary arteriography, left and right heart biopsies, and invasive measurements of contractility, as well as therapeutic tools including aortocoronary bypass surgery, percutaneous transluminal coronary angioplasty, and a broad field of pharmacological interventions for the whole spectrum of cardiovascular diseases, especially chronic heart failure. It was during the 1990s that the scientific world focused on the evolution of molecular biology of the cardiovascular system so that cardiovascular physiology seemed to become less important. Regarding the myocardium, molecular alterations of important functional proteins (phenotype changes), as well as signal transduction pathways of contractility and cardiac growth have been elucidated. The functional importance of a number of genes has been proven with the help of transgenic animals.This work provides an overview for researchers and practioners interested in the broad field of molecular biology and physiology of the cardiovascular system.

This book is an attempt to indicate to researchers and clinicians a simple way to approach the complexity of cardiovascular neural regulation. A conceptual pillar like homeostasis is contrasted with instability and a continuous interaction of opposing mechanisms that have negative and positive feedback characteristics, and is considered to subserve the multitude of patterns pertaining to physiology. However, in pathophysiological conditions the final design is most often replaced by largely purposeless neural mechanisms. The complexity of cardiovascular neural regulation, reflected by the state of sympathovagal balance, is also assessed in the frequency domain. Power spectrum analysis of heart rate and arterial pressure variability, a sophisticated but simply explained approach, provides an unprecedented tool to evaluate this interaction in both physiological and pathophysiological conditions. The elementary characteristics of nonlinear dynamics are also outlined. Finally, the need for an ethical structure for science and medicine is analyzed.

A general reference text concerned with the biology of the vascular cells and the blood vessel wall under physiological and pathological conditions. One of the major functions of the arteries is to maintain a continuous blood flow to the organs whatever the pressure conditions, thanks to the vasomotor tone of the smooth muscle cells. Great advances have been made over the last decade in the understanding of the endothelial cells as integrators and transducers of signals originating from the blood stream. The pluripotent control functions of the endothelial cells in the vessel wall are now well recognized. A review of endothelial functions and dysfunctions is presented. Cell biology and molecular genetic studies have now identified an array of molecules elaborated by endothelial cells and vascular smooth muscle cells and by the blood-borne elements which interact with artery cells, defending the artery against injury and modulating evolving abnormal processes. Molecules which induce or inhibit endothelial and/or smooth muscle cells are under great scrutiny in the late 1990s.Angiogenesis, which plays a major role in tumour growth, but may also be beneficial as a healing process in muscle ischemia, is discussed. Apoptosis, or programmed cell death, has only recently been recognized as an essential process in blood vessel modelling and remodelling. An overview of apoptosis in the vascular system is presented. It is increasingly evident that the adjustments of the blood vessel wall are made in the presence of deforming disease processes such as hypertension and atherosclerosis. The second part of the book is concerned with the blood vessel wall in disease conditions. Several chapters review the role of the vessel and vascular cells in inflammation, and vascular remodelling during arterial hypertension and aging. One chapter is devoted to atherogenesis, atheroma and plaque instability, followed by the pathophysiology of post-angioplasty restenosis, which is a crucial issue in modern interventional cardiology.

Cardiology is an area of great recent triumphs in pharmacological and surgical treatment, yet cardiovascular disease remains the leading cause of death and disability in the industrialized world. Coronary disease, heart failure, stroke and sudden arrhythmic cardiac death challenge both medical practitioners and scientists. With the dawning of the new `molecular' era, there is an awakened hope that a more fundamental understanding of biologic processes may eventually lead to new progress in the prevention and treatment of these persistent and seemingly intransigent problems. Molecular Cardiology in Clinical Practice brings together a panel of experts in cardiovascular disease who have been at the forefront of the application of molecular medicine to cardiology. Its intent is to help bridge the gap between modern medical practice and modern science, in the belief that an understanding of basic principles can lead to new insight into the problems of cardiac patients.

This text has been divided into six parts. The first part describes the differences between hypoxia and ischemia, animal models, the effects of ischemia on myocardial function and metabolism and the electrophysiological consequences of ischemia. The second part deals with the mechanisms of cardiomyocyte death in ischemia, structural aspects of irreversible ischemic injury, the role of calcium and the concept of calcium antagonism. The third chapter is a brief description of reperfusion injury, its clinical relevance and possible prevention. The fourth part summarizes changes in myocardial vasculature during ischemia and reperfusion. The fifth part is the survey of two main possibilities for increasing cardiac resistance to ischemia and hypoxia for long-lasting adaptation to chronic hypoxia and short-lasting preconditioning. The last part of the book deals with comparative and ontogenetic aspects of cardiac sensitivity to oxygen deprivation; this chapter also summarizes the ontogenetic differences and limitations in endogenous and exogenous protection of the ischemic/hypoxic heart.

Apoptosis or programmed cell death is increasingly considered to be a major factor in the development and progression of cardiovascular disease. In patients with heart failure the activation of apoptosis may result in the loss of irreplaceable cardiac myocytes promoting the clinical course of the syndrome. Moreover, in the coronary arteries inflammation and apoptosis may weaken critical structures of the vessel wall leading to plaque rupture and, subsequently, to myocardial infarction. Given these deleterious consequences, it seems almost paradoxical that programmed cell death is an active process that, if initiated under physiological circumstances, is essential for both coordinated tissue growth or destruction of malignant cells. This text provides a synopsis of basic mechanisms, cellular and structural targets and, finally, clinical implications of programmed cell death in the heart. The authors of this volume give concise overviews on general and cell-specific aspects of programmed cell death in cardiac myocytes and fibroblasts, as well as in vascular smooth muscle and endothelial cells.Furthermore, novel therapeutic options arising from the outstanding pathophysiological significance of cardiac apoptosis are presented.

ATP plays a central role in the two leading causes of cardiac morbidity and mortality in the western world: ischemia and heart failure. We are in our infancy applying what is known about biology and chemistry of ATP toward developing effective therapies for these diseases. In this volume, the current understanding of the chemistry and biology of ATP specifically in the cardiomyocyte is presented. Insights into ATP have been gleaned using biophysical techniques allowing dynamic measurement of chemical events in the intact beating heart and using animal models in which cardiac proteins are either over expressed, deleted or harbour specific mutations.

This text reviews how heart cells communicate and impulse propagation under normal as well as under pathological conditions. The complexity of intercellular coupling and impulse propagation is discussed, providing the reader with a broad view of the importance of these processes and how they contribute to the generation of cardiac arrhythmias and heart failure.

This volume discusses the current concepts of the pathophysiology of coronary circulation and methods to measure coronary vasodilatation, with a focus on noninvasive transthoracic doppler echocardiography. In addition, it provides practical insights for patient management.

This is a concise, but comprehensive volume for clinical cardiologists or medical students interested in learning how molecular genetics is being applied to prevention and treatment of heart diseases, from DNA tests to pharmacogenomics and gene-based therapeutics. The volume, written in a plain language, contains detailed figures. A rich glossary, three appendices, many references and several URLs provide additional sources of information.

This title offers a comprehensive overview of vein physiology. It presents: data in the fields of venous physiology, pharmacology and venous diseases as well as the field of phlebology; developments in venous disorders, with regard to pathophysiology; most modern diagnostic methods and therapies; and venous tone regulation data. There are take home messages at the beginning of each chapter for quick review and a list of key abbreviations used in the book.

This latest volume in the "Basic Science for the Cardiologist" book series is dedicated to the study of the physiological genomics of cardiovascular disease. It was inspired by the Third Amsterdam Mouse Symposium which showed the enormous strides that have been made in physiological genomics in recent years. The integrative nature of this field has its best clinical analogue in critical care medicine where the cardiovascular system, and the diagnosis and treatment of the different organ systems and their successful interaction are key. Physiological monitoring, mechanical ventilation, sedation and an integrative analysis all form part of the arsenal of the intensivist and also of the mouse physiologist. Sections include the following: physiological monitoring of the mouse; cardiovascular pathophysiology of the mouse; and treating the critically ill mouse.

Hemodynamics makes it possible to characterize in a quantitative way, the function of the heart and arterial system, thereby producing information about what genetic and molecular processes are of importance for cardiovascular function.Snapshots of Hemodynamics: An Aid for Clinical Research and Graduate Education by Nico Westerhof, Nikos Stergiopulos and Mark I. M. Noble is a quick reference guide designed to help basic and clinical researchers as well as graduate students to understand hemodynamics. The layout of the book provides short and independent chapters that provide teaching diagrams as well as clear descriptions of the essentials of basic and applied principles of hemodynamics. References are provided at the end of each chapter for further reading and reference.Nico Westerhof, PhD is affiliated with the Laboratory for Physiology at VU University Medical Center in Amsterdam, The Netherlands.Nikos Stergiopulos, PhD is affiliated with the Laboratory of Hemodynamics and Cardiovascular Technology at the Swiss Federal Institute of Technology in Lausanne, Switzerland.Mark IM Noble, DSc, MD, PhD is affiliated with Cardiovascular Medicine at Aberdeen University, Aberdeen Royal Infirmary in Aberdeen, Scotland.

Cardiac Ischemia: From Injury to Protection has been divided into six parts. The first part describes the differences between hypoxia and ischemia, animal models, the effects of ischemia on myocardial function and metabolism, and the electrophysiological consequences of ischemia. The second part deals with the mechanisms of cardiomyocyte death in ischemia, structural aspects of irreversible ischemic injury, necrosis and apoptosis of cardiac cells, the role of calcium, and the concept of calcium antagonism. The third chapter is a brief description of reperfusion injury, its clinical relevance, and possible prevention. The fourth part summarizes changes in myocardial vasculature during ischemia and reperfusion. The fifth part is the survey of two main possibilities for increasing cardiac resistance to ischemia and hypoxia, i.e. long-lasting adaptation to chronic hypoxia and short-lasting preconditioning. The last part of the book deals with comparative and ontogenetic aspects of cardiac sensitivity to oxygen deprivation; this chapter also summarizes the ontogenetic differences and limitations in endogenous and exogenous protection of the ischemic/hypoxic heart.

Clinical Physiology of the Venous System is a comprehensive overview of vein physiology. - Presents data in the fields of venous physiology, pharmacology and venous diseases as well as the field of phlebology, which has seen rapid and important progress in the last decade.

The physiological genomics of the cardiovascular system studies the relationship between gene and physiological (dys)function. It is a rapidly developing area of research and distinguishes itself from other areas of molecular medicine by its highly integrative nature. In this multi­ disciplinarian area of the physiological sciences, there is interaction between gene structure and physiological cardiovascular function as well as interactions between the different organs and their physiological compartments. The mouse has played a central role in the study of genomics due to the detailed knowledge of the mouse genome and the wide availability of genetically modified mice. In the past, the mouse had mainly been used in the area of immunology and molecular biology, and physiological interest in the mouse was scarce. As more insight has come into the structural genomics of the mouse, however, it has become increasingly important to understand the relation between gene and physiological function. With this in mind we have been organizing the Amsterdam Mouse Symposia to bring together different disciplines interested in the molecular basis of cardiovascular function (see J. of Clinical and Exp. Pharmacology and rd Physiology (2002) 29:A69-AI02 for the proceedings of the 3 Amsterdam Mouse Symposium and Basic Research in Cardiology (2000) 95:492-535 for nd the proceedings of the 2 symposium).

During several decades of this century, the classical physiological studies on the cardiovascular system have greatly improved our knowledge on the function of this system under normal and pathological conditions. This knowledge was the basis of the breakthrough for diagnostic techniques like the Swan-Ganz catheter, coronary arteriography, left and right heart biopsies, and invasive measurements of contractility, as well as therapeutic tools including aortocoronary bypass surgery, percutanous transluminal coronary angioplasty, and a broad field of pharmacological interventions for the whole spectrum of cardiovascular diseases, especially chronic heart failure. It was during the last decade that the scientific world focused on the evolution of molecular biology of the cardiovascular system so that cardiovascular physiology seemed to become less important. Regarding the myocardium, molecular alterations of important functional proteins (phenotype changes), as well as signal transduction pathways of contractility and cardiac growth have been elucidated. The functional importance of a number of genes has undoubtedly been proven with the help of transgenic animals. Mechanics and Energetics of the Myocardium provides an overview for those researchers and practioners interested in the broad field of molecular biology and physiology of the cardiovascular system.

Genetics and Genomics for the Cardiologist is a concise, but comprehensive volume for the clinical cardiologist or medical student interested in learning how molecular genetics is now being applied to prevention and treatment of heart diseases, from DNA tests to pharmacogenomics and gene-based therapeutics.

ATP plays a central role in the two leading causes of cardiac morbidity and mortality in the western world: ischemia and heart failure. We are in our infancy applying what is known about biology and chemistry of ATP toward developing effective therapies for these diseases. In this volume, the current understanding of the chemistry and biology of ATP specifically in the cardiomyocyte is presented. New insights into ATP have been gleaned using biophysical techniques allowing dynamic measurement of chemical events in the intact beating heart and using new animal models in which cardiac proteins are either over expressed, deleted or harbor specific mutations. This book provides a summary of the basic understanding and includes illustrations of why ATP and the Heart is important to both the clinician and scientist.

Coronary flow reserve is an important functional parameter to understand the pathophysiology of coronary circulation.

Heart Cell Coupling and Impulse Propagation in Health and Disease includes an up-to-date review on how heart cells communicate and impulse propagation under normal as well as under pathological conditions. The complexity of intercellular coupling and impulse propagation is discussed, providing the reader with a broad view of the importance of these processes and how they contribute to the generation of cardiac arrhythmias and heart failure. The different aspects and intricacies of heart cell communication is discussed by different authors, each one an expert in their own field. The present publication will be of interest to cardiologists, electrophysiologists, heart physiologists, cardiac pharmacologists, biophysicists, and cell or molecular biologists.

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

Profound mortality rates, due to cardiovascular disease, are a worldwide problem. Cardiovascular disease results from complications of a silent and chronic arterial disease: atherosclerosis.