Recent progress in recombinant DNA technology and the availability of a number of nonpeptide subtype-specific receptor antagonists and of specific antibodies to components of prorenin-renin-angiotensin system (PRAS) have led to rapid advances in the under standing of the multifaceted role of angiotensin II, classically known as a peptide hormone of cardiovascular homeostasis. Accumulating evidence sug responsible for the regulation gests that, in addition to its role in salt and water metabolism, PRAS may control other physiological functions including neurosecretion, cellular proliferation, hypertrophy and/or differentiation, angiogenesis and gonadal function. At the same time, it is becoming evident that the specialized functions of endocrine glands are not only regulated by trophic hormones but also by locally produced paracrine/autocrine factors. The concept is emerging that tissue PRAS is one such locally active regulatory system. With more and more reproductive and endocrine organs being added to the list of tissues that contain a local tissue PRAS, questions are being raised by the reproductive biologists and endocrinologists as to the role of such systems in the tissues of their interest. On the other hand, the cardiovascular and renovascular physiologists are wondering about the relevance of PRAS in various peripheral tissues compared to those of the classical cardiovascular organs. It appeared, therefore, that the time was ripe for a meeting to consider a merger of interest in these two important but heretofore distinct areas of physiology."

From molecule to man: Medical research has indeed taken this direction, and major improvements of our understanding of the pathophysiology and epidemiology of disease have been achieved. The molecular basis of the congenital cardiovascular disorders has been extended from relatively few congenital malformations into everyday illnesses such as diabetes mellitus, hyperlipoproteinaemea, and arterial hypertension. The monogenic and, more difficult, polygenic basis for a vast majority of cardiovascular disorders are being defined more precisely from year to year. This book gives an overview of what has been achieved so far and defines the current position.

This comprehensive volume provides a detailed review on the general work up of chronic kidney disease-associated resistant hypertension. This title is separated into four parts; the first of which provides definitions, epidemiology, characteristics, risk stratification and outcomes of resistant and apparent treatment resistant hypertension. The next two sections explore pathophysiology and diagnosis, treatment in the light of new guidelines, as well as procedures and devices for neural modulation. Part four discusses public health approaches to resistant hypertension, educational programs, and resistant hypertension for general practitioners. Resistant Hypertension in CKD brings up-to-date information to nephrologists, internists, cardiologists and a wide array of other clinicians and health professionals taking care of chronic kidney disease patients.

After a certain age, one is elderly, aged, venerable, and patriarchal. Or just plain old. When I became old, I did not know it. I do know it now because of a syndrome of which I had previously been unaware. It is quite simple-when it hurts, it works; when it doesn't hurt, it doesn't work! Writing about the old is a preoccupation of the young, and that is as it should be because it is the young who must carry the burden of the old. I don't know the average age of the contributors to Franz Messerli's book, but I would guess it to be less than 50, which to me is positively pubescent! For many years I thought geriatric medicine was nonsense, and today I still think some of it is. What changes with age are principally the attitude and purposes of the individual and how much energy he or she has to carry out those purposes. It isn't so much that the goals, ambitions, and desire to alter or improve the world disappear; they just diminish along with what it takes to accomplish them. Which brings me to one particular aspect of aging, that is, the cardiovascular system. The first evidence of the cardiovascular system's aging is the failure of the heart to respond to the demands placed on it.

Hypoxic Pulmonary Vasoconstriction: Cellular and Molecular Mechanisms will provide a timely and long lasting guide for investigators in the fields of cardiovascular physiology and pathophysiology, pulmonary vascular disease, high-altitude physiology and medicine. In addition, it provides a solid scientific foundation for subsequent applications in clinical practice.
The volume is divided into eight sections:
- Physiology and Pathophysiology of HPV
- Role of Intracellular Ca2] and Ca2+ sensitivity in HPV
- Role of Ion Channels in HPV
- Role of the Endothelium in HPV
- Mechanisms of Oxygen Sensing in the Pulmonary Vasculature
- Oxygen-Sensing Mechanisms in other Organs and Tissues
- Pathology and Mechanisms of Hypoxia-Induced Pulmonary Hypertension
- Experimental Models for the Study of HPV.

State-of-the-art findings relevant to cellular and molecular processes of hypoxic pulmonary vasoconstriction as well as knowledge regarding etiological mechanisms and experimental therapeutics are well covered and complete the overview this volume provides.

Cerebral amyloid angiopathy (CAA) is a distinctive abnormality of small cerebral blood vessels, one that has intrigued neuroscientists for decades. The time seems right for a book which examines the phenomenon of CAA using a multifaceted approach: What does it produce clinically? How might CAA be imaged? What are the crucial biochemical/cellular events within cerebral vessel walls that lead to CAA? How can in vitro or transgenic experimental systems be used to understand the etiology of, or even potential treatments for, CAA? The editors have assembled key figures in the field of CAA research to examine these (and other) questions in a series of focused chapters that address specific issues of importance in understanding CAA and its clinical manifestations. Comprehending the biology and pathogenesis of this fascinating vascular lesion may even provide clues to less common forms of cerebral microvascular disease that have been recognized for decades (hypertensive microangiopathy) or more recently (CADASIL).

Because the increasing complexities of diagnos testing and training, for example) are of neces ing and treating coronary artery disease are at sity discussed in more than one chapter with times overwhelming for many physicians, the appropriate cross referencing. Special attention purpose of this book is to bring together in one has been directed at making the references as comprehensive yet reasonably concise text a current as possible. Since the aim of the book is to do more than just update the concepts, the scholarly but clinically oriented analysis of the reader is also informed of the pertinent contro major aspects of coronary artery disease. The book is mainly intended for internists versies in the field. The word controversy is used in its most liberal form, so as to include areas of and clinical cardiologists as well as for those in training for these respective disciplines, but it disagreement or of uncertainty as well as should also be of interest to primary care physi changes in traditional views. Each of the con cians responsible for the management of pa tributors has been asked to identify specifically tients with coronary artery disease. Each of the the most important of the controversies in his contributors-whether cardiologist, radiologist, particular area of interest and to address himself or surgeon-has been selected for his special to these issues in the course of the chapter."

Pediatric cardiology is celebrating in the 1990s the 50th anniversary of the beginnings of the age of therapy. This informal `history' describes how the discipline grew from the era of pathologic anatomy to the dawn of therapy, the beginnings of closed heart surgery between 1939 and 1945. That dawn ushered in a remarkable half century of change and growth, leading from clinicophysiologic correlations through the start of open heart surgery in the 1950s. The text celebrates some of the achievements of this vivid and heroic age, and describes how, in the mid 1970s, new surgical and medical approaches, including prostaglandins and Doppler echocardiography, led to successful cardiac treatment in infancy, the `infant era'. Interventional cardiology and the study of childhood arrhythmias began. Now, in the 1990s, a new era emphasising molecular biology and cardiac development is growing from the tools and concepts of the past. The four eras have focused on pathologic anatomy, clinicophysiologic correlations and surgery, heart problems in infancy, and now the developing heart. In each era there have been advances in the four domains of pediatric cardiology, the heart before birth, the normal heart, heart disease and defects, and preventive cardiology. Growth in knowledge has been both episodic and dramatic, yet not a picture of unalloyed achievement. The later chapters discuss some of the problems beginning to be recognised in the new and current `developmental era'. The pioneers of pediatric cardiology, both men and women, are more than eponyms, for each used in new and original ways the tools and concepts available in their era. The interaction of tools and concepts is a theme in this book. Just as the tool of the stethoscope was vital in delineating the clinical profile of ventricular septal defect and patent ductus, the fluoroscope played a role in developing the concept of the Blalock Taussig shunt. Pioneers also include patients and their families, and the book includes some discussion of what little is known of childhood and of the child with heart disease in the four different eras. This is a brief overview of the growth of knowledge of children's hearts from before William Harvey until our own time, and includes references to histories of cardiac surgery and to collections of classic cardiac papers. By its emphasis on the child as the central historic figure, and on the interaction of tools and concepts in the growth of knowledge, the text provides a celebratory approach to the 50th anniversary of modern pediatric cardiology.

It is quite natural that literature related to car heart disease, cardiomyopathy, pulmonary and diac structure, function, pathology, and patho pulmonary vascular disease, trauma, acquired valvular disease, congenital disease, and surgi physiology has emphasized the left heart and systemic circulation. The relative lack of im cal considerations. The pathologic and clinical relevance of myocardial infarction of the right portance of the right ventricle was supported by studies performed in the 1940s and 1950s ventricle has only been documented over the which suggested that the right ventricular free last 15 years. The chapter on right ventricular wall could be effectively destroyed in an animal infarction integrates clinical, functional, patho model without detectable untoward hemody physiologic, and pathologic observations to pro namic consequences. The relative inadequacy vide the reader with a thorough review, equally of noninvasive tools to study right ventricular relevant to the clinician and investigator. The contribution on dilated cardiomyopathy pro structure and function obviated detailed and systematic investigation. However, over the vides novel insight into the impact of right ventricular performance on the functional in past 15 years there has been a resurgence of interest in the right ventricle by a variety of capacity accompanying left heart failure. A book dealing with the right ventricle would investigators. The skeptic would argue that this renewed interest resulted from an exhaustion be incomplete without at least cursory reference we have of clinically-related observations that could be to the pulmonary circulation."

Cardiac Gene Expression: Methods and Protocols presents both cutting-edge and established methods for studying cardiac gene expression. The protocols provide a template for solid research, and cover the process through screening, analysis, characterization, and functional confirmation of novel genes or known genes with a new function.
Section I, Cardiac Gene Expression Profiling: The Global Perspective, discusses several different approaches to examining, identifying, and analyzing changes in transcriptome gene expression. Section II, Cardiac Gene Regulation: Gene-Specific mRNA Measurement in the Myocardium, outlines more sensitive and gene-targeted expression methods. Section III, Cardiac Gene Regulation: Promoter Characterization in the Myocardium, provides protocols for the study of underlying gene regulation mechanisms by focusing on the interaction of transcription factors with their cognate cis binding elements. Section IV, In Silico Assessment of Regulatory cis-Elements and Gene Regulation, and Section V, Cardiac Single Network Polymorphisms, emphasize new analytical approaches for deciphering the functional elements buried in the 3 billion nucleotides of the human genome and other model genomes. The concluding section, Gene Overexpression and Targeting in the Myocardium, highlights methods that facilitate overexpression or cardiac-specific targeted gene deletion.

Over the past 25 years, the growing impor cardiovascular. We hope that by having this tance of genetic factors in the basic understand compilation of cardiovascular diseases in one ing of human cardiovascular disease has become source, it will be of value to all who are involved apparent. Prior to this time, there was an era in the care of patients with cardiovascular dis when cardiovascular disease was first viewed at ease or their families. the diagnostic level followed by an era when The first six chapters of this book delineate cardiovascular disease was viewed at a treatment conditions related to congenital cardiac mal level. The first era occurred at the turn of the formations. Their etiology is not precisely century with the first clinical recognition of known, so we have included chapters that dis symptoms and patterns for diagnosis of car cuss many aspects of congenital cardiac mal diovascular diseases. The development of formations. The first chapter provides discus diagnostic methodology, such as radiographic sion of mechanisms of maldevelopment of the studies and electrocardiography, led to marked heart. We believe that these mechanisms pro changes in our understanding of cardiovascular vide a basis for understanding the genetic and disease. This era was followed by improved environmental factors which operate to produce methods of medical treatment, introduction congenital cardiac malformations. Chapter 2 describes the occurrence of con of medication such as antibiotics, and more genital cardiac malformations in families and sophisticated surgical techniques."

1. Magnetic resonance imaging: A new approach for evaluating coronary artery disease?.- 2. Coronary circulation.- 3. Magnetic resonance imaging and quantitation of blood flow.- 4. Imaging strategy in cardiac magnetic resonance imaging.- 5. MRI determination of cardiac dimensions.- 6. Visualization of the coronary arteries.- 7. Magnetic resonance imaging of myocardial ischemia and infarction in experimental animal models.- 8. Magnetic resonance imaging in acute myocardial infarction.- 9. Assesment of myocardial infarction by magnetic resonance imaging with the aid of contrast agents.- 10. MRI: Evaluation of ventricular function in coronary artery disease.- 11. Stress magnetic resonance imaging in coronary artery disease.- 12. Visualization of coronary artery bypasses with MRI.- 13. Recent advances of magnetic resonance spectroscopy in myocardial ischemia.

Attention to reducing the major risk factors Contemporary coronary care involves a associated with the development of arterio multitude of measures: efforts to prevent the sclerosis has been widespread and appears to acute event; thrombolytic therapy to abort have lowered the incidence of coronary artery infarction; pharmacological measures to delay disease. Nevertheless, acute myocardial and reduce ischemic cell death; monitoring of infarction and related ischemic syndromes the hemodynamic consequences of myocardial represent the most common causes of death as infarction; treatment of acute pump failure; use well as one of the principal reasons for of modern electrical devices as well as a large hospitalization in the industrialized world. In number of new drugs to prevent and treat light of this, care of the patient with acute cardiac arrhythmias; and finally, identification coronary disease remains a major medical prior to hospital discharge of patients who are at challenge. high risk for recurrent infarction or sudden The approach to managing patients with death and the choice of the appropriate acute myocardial infarction can be said to have management approach. evolved through three major phases. For the This fine book provides comprehensive first half-century after Herrick's landmark descriptions of these various aspects of paper describing this condition was published in contemporary coronary care. It is accurate, 1912, management consisted primarily of thorough, and easily readable."

Heart Hypertrophy and Failure brings together leading basic scientists and clinicians, presenting improved knowledge of the pathophysiology and treatment of the condition. The result is a synthesis of state-of-the-art information on molecular biology, cellular physiology and structure-function relationships in the cardiovascular system in health and disease. The papers presented describe fundamental mechanisms underlying changes in the cellular machinery during the development of cardiac hypertrophy and heart failure. Audience: Students, scientists, clinical and experimental cardiologists who seek to understand and manage the perplexing problems of hypertrophy and heart failure.

What we now call a deep venous thrombosisa (TM) (DVT) has been elucidated by a diversity of investigative approaches during the past four centuries. The authors of this book survey the history of the field and ask: why has one of these perspectives a the haematological/biochemical a come to dominate research into the causation of DVT during the past 50 years and to exclude alternatives? In answering this question, they show that the current consensus model is conceptually flawed. Building on the work of William Harvey, John Hunter, Rudolf Virchow, Ludwig Aschoff and a number of pathologists in the mid-20th century, they offer a revised account of the aetiology of this condition. In the process they retrace and review the 160-year-old philosophical and methodological schism in biomedical research and, using DVT as an example, propose how this schism might be bridged to the benefit of both research and clinical practice.

This book provides an overview of the etiology of coronary artery disease and focuses on the main therapies and drug interventions currently available. It highlights drug pharmacology and therapeutic challenges, with a special emphasis on the underlying principles of available therapeutics and the on-going development of drugs for coronary artery disease. The book is divided into eight chapters, the first of which describes the classical mechanism of coronary artery disease and its clinical presentations. Chapter 2 lists the principles of and related evidence on the prevention and treatment of coronary artery disease. This includes diet and lifestyle management, and guidelines for the treatment of acute coronary syndrome and stable coronary artery disease. In turn, Chapter 3 describes revascularization treatments, covering percutaneous coronary interventions, coronary artery bypass grafts and thrombolysis. This chapter also addresses the main therapeutic challenges. The following chapters provide an overview of three major categories of coronary artery disease drugs, which target thrombosis (Chapter 4), lipid metabolism (Chapter 5), and hypertension (Chapter 6). Heart failure constitutes the major health burden in the late stage of coronary artery disease; accordingly, current heart failure therapeutics and related drug pharmacology are described in Chapter 7. In closing, Chapter 8 provides a summary of on-going clinical trials for coronary artery disease drug development and discusses a number of promising areas in which intensive research into new therapeutics is being pursued. Given its scope, the book will be of interest to clinicians, medical students and research scientists, as well as to pharmaceutical professionals who are seeking new therapies and drugs for coronary artery disease and related disorders.

On 16 October 1846, an itinerant New England dentist named William T. G. Morton proved the anesthetic effect of diethyl ether in a public demonstration in the "ether dome" of the Bulfinch Building of the Massachusetts General Hospital in Boston. The patient, Gilbert Abbott, suffered no pain, and the surgeon, Dr. John C. Warren, was able to complete a suture ligature of a vas cular tumor of the jaw without the hurry that until then was so necessary. The operation proved a failure, since the tumor recurred; but the demonstration of ether's anesthetic effect was a great success. Operative pain was conquered, and surgery could advance from a crude and unscientific practice where speed was paramount, and the major body cavities could not be entered, into the unique blend of science and art that it is now. "Gentlemen, this is no hum bug," supposedly muttered Warren, perhaps the last noncontroversial assess ment of anesthesiology to be made by a surgeon. The screams of resisting patients in pain were stilled, and quiet entered the operating room for the first time. But the new science of pain relief was quickly wrapped in controversy. An argument immediately arose as to who could legitimately claim primacy for the discovery. Morton's attempt to hide the true nature of his anesthetic agent, coupled with an effort to patent the discovery, clouded his reputation and stimulated other claimants to push themselves forward."

A qualitative leap in the understanding of cardiovascular and n- ral regulation by the renin-angiotensin system, and of the role of this s- tem in tissue damage, has occurred as a result of the many recent advances in molecular genetic techniques. The cloning of the genes for the components of the renin-angiotensin system, the design of specific angiotensin receptor ligands, and the use of embryonic gene targeting te- niques for the creation of mutant strains have established that the renin- angiotensin system is important in blood pressure regulation, ion and fluid homeostasis, and tissue growth and remodeling Further investigation of the mechanisms by which this system p- ticipates in cardiovascular regulation may shed some light on the pat- genesis of several cardiovascular diseases, e. g. , hypertension, congestive heart failure, and chronic renal failure. Despite the promise of this system as a target for therapeutic interventions for these diseases, there are great challenges in the integration of the attempts to close the gap between the traditional literature of medicine and the explosion of information from the new technologies. This book's title, Angiotensin Protocols, reflects the authors' strong efforts to translate expert knowledge into easy-to-follow practice. The book opens with introductory chapters, and each specialty section provides detailed methods covering a wide variety of techniques, ranging from genetic manipulation of targeted genes to functional studies of the renin- angiotensin system.

This award-winning thesis investigates the mechanisms underlying cardiac arrhythmia development and termination from an entirely new perspective. By viewing the heart as a complex system, the author uses theoretical tools from nonlinear dynamics combined with numerical simulations and experiments to achieve insights into the relationship between its structure and dynamics, thereby paving the way towards innovative low-energy defibrillation strategies. The work tackles, among other things: the effect of substrate heterogeneity on the spatial-temporal dynamics of cardiac arrhythmias and ways in which weak pulsed electric fields can be used to control these dynamics in heterogeneous cardiac tissue. The long-term vision of this research is to replace the current strategy of applying painful and sometimes tissue damaging electric shock - currently the only reliable way to terminate life-threatening fibrillation - by a more subtle but equally effective intervention. The book maps out a number of promising research directions for biophysicists and medical researchers working on the origins and treatment of cardiac arrhythmias.

The most salient feature of the infor last four chapters of the book evaluate the mation provided by nuclear medicine is its information from an analytical and pathophysiological and functional charac statistical point of view. This approach is ter. For adequate experimental or clinical required for correct decision-making. interpretation, such information should This book is therefore the result of necessarily be interpreted alongside the accumulated experience in nuclear cardiology views of the clinical cardiologist, who is with the invaluable cooperation of medical able to apply it to the individual patient. statisticians. It is directed to physicians This approach, which is routine in every with an interest in nuclear cardiology, to day clinical practice, reaches its plenitude nuclear medicine specialists wishing to when the whole process is completed and learn the uses and limitations of these an intimate cooperation is established procedures in everyday clinical cardiology, between the nuclear medicine specialist and to cardiologists who feel the need to and the clinical cardiologist. In such understand the rationale and methodology instances, each one of these professionals of the studies which benefit their patients. understands the needs, limits and possi We understand that the ultimate reason bilities of the other. for any scientific book is the transmission The present book is the fruit of such of knowledge, and we are fully conscious cooperation. In our hospital, an efficient of the enthusiasm of the authors of the nuclear cardiology team has been made up present text to achieve that aim.

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.