Pawan K. Singal - Böcker

Diabetes and cardiovascular disease together account for the largest portion of health care spending compared to all other diseases in Western society. This work seeks to provide an understanding of the causes of diabetes and its cardiovascular complications. As this understanding becomes more widely appreciated, it may serve as a foundation for evidence-based care and wider acceptance of sound science. The International Conference on Diabetes and Cardiovascular Disease, held in Winnipeg, in June 1999, was organized to bring together a multi-disciplinary group of researchers dedicated to further knowledge amongst researchers, care givers, and the managers of the health system. The invited speakers submitted their works for publication, which serves as the basis for this book. Major themes include: epidemiology of diabetes mellitus, metabolic risk factors in diabetes and cardiovascular disease, hypertension in diabetes mellitus, cardiac function in diabetes, glycemic control and improved cardiovascular function, diabetes management, and endothelial function in diabetes.

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

This volume brings together leading basic scientists and clinicians, presenting new approaches to the complex problem of heart failure, involving cardiomyopathic processes and ischemia perfusion injury. The result is a synthesis of 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. This book is intended for clinical and experimental cardiologists.

This special issue of Molecular and Cellular Biochemistry our their mentor. The ex-students and trainees came from contains original research articles and review papers which all over Canada, the United States, Japan, Slovakia, Ger- were invitedfrom the participants ofa recent meeting organ- many, the Czech Republic, Estoniaand the Netherlands. The izedto honourthe 60th birthdayofNaranjan S. Dhalla, Ph.D., meeting wasjudged to be an overwhelming success in terms M.D. (Hon.). The meeting, organized by Drs. Morris Karma- ofthe scientific content as well as collaborative interactions zyn (London), Grant Pierce (Winnipeg) and Balwant Tuana initiated. (Ottawa), was held at the Best Western Lakeside Inn in We gratefully acknowledge the financial support from Kenora, Ontario, Canada from August 23-25th, 1996. The Pfizer, MerckFrosst, Astra, Ciba-Geigy, the Heart and Stroke meeting was entitled 'The Cellular Basis of Cardiovascular Foundation of Manitoba, the Medical Research Council of Function in Health and Disease'. There were over40 invited Canada, St.Boniface Research Foundation, the NRC Insti- speakers from 15 different countries present at the meet- tute for Biodiagnostics, the ManitobaHealth Research Coun- ing and it was attended by over 280 people. Keynote lectures cil and various sources within the University of Manitoba.

Over two centuries ago, oxygen was discovered as "air vital": the component of the earth's atmosphere necessary for life. Less than five years after this discovery, it was found that oxygen was both a life-sustaining and life threatening inhalant as it plays a role in the two extremes of the animal kingdom: life and death. In the subse­ quent years, we have made major strides in understanding the role of oxygen in maintaining life and volumes of information are now available on this topic. Our knowledge of the contribution of oxygen in cellular dysfunction and cell death which for the most part had lagged behind has begun to catch up. The deleterious ef­ fects of oxygen radicals and activated oxygen species on a variety of biological systems have now been described. Recently attention has also been focused on the toxic effects of oxygen on the cardiovascular system. The major aim of the present treatise is to offer an integrated view of the pathophysiological aspects of oxygen toxicity in the heart and blood vessels coupled with a review of therapeutic approaches (hopes?) with free radical scavengers and antioxidants. Internationally known expert investigators provide a concise and critical review on the topic of their expertise which also contains data from their own research.

It has been known or suspected for centuries that there is an association between mind and emotions and the occurrence of heart disease apd sudden death. During the past fifty years this relationship has become identified with the concept of Stress, a notion developed and popularized by Hans Selye. In recent years there has been an upward surge of interest in stress by scientists in several disciplines and by the general public. Although, books, journal articles, seminars and media programs devoted to stress now abound, the definition, manifestations, mechanisms, and management of stress remain uncertain and controversial. In an attempt to clarify the situation an International Symposium on Stress and Heart Disease was held in Winnipeg, Canada, June 26-29, 1984, and the proceedings form the basis of this book and its companion volume "Patho­ genesis of Stress-Induced Heart Disease". Although most species which have ever existed are now extinct through countless millenia, the human species has successfully adapted to changing conditions ("stressors") such as ice ages, predators and parasites, wars, famine and plague, and now it is coping with rapidly changing social, economic and political circumstances. Such adaptation occurs at all levels of life- at the molecular level within the cell, at the level of the whole cell, in the groups of cells as organs, in the entire organism or individual, and in some cases, in the society in which the individual lives.

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

The importance of the developmental approach for experimental and clinical cardiology is indisputable. Clinical-epidemiological studies have clearly shown that the risk factors of serious cardiovascular diseases, such as atherosclerosis and ischemic heart disease, are already present during the early phases of ontogenetic development. Furthermore, congenital cardiovascular malformations remain the single largest cause of infant mortality from congenital defects in industrial countries. It is therefore not surprising that the interest of theoretical and clinical cardiologists in the developmental approach keeps increasing. Advances in molecular biology accelerated this trend substantially. This book is based on contributions presented at the international symposium The Developing Heart in Prague in May 2000. It should stimulate the curiosity of cardiovascular scientists in gaining insight into the mechanisms of normal and pathological development.

The limitation in number of donor hearts led to the establishment of alternative treatments such as left ventricular assist devices (LVAD), which have been used. Although several reports suggest the native ventricular function recovers after long-term LVAD support - a process called "reverse remodelling" - the underlying biological mechanisms are unclarified. Various molecular pathways of the human myocardium associated with apoptosis, response to stress, or matrix changes are known to be altered under conditions of heart failure and some of them have been shown to be reversible regulated during left ventricular mechanical support. This suggests that the "reverse remodelling" is actually, at least in part, a reverse mechanism. One explanation may be, under mechanical circulatory assist, volume and pressure overload is reduced, and thus ventricular wall stress decreases, leading to improved myocardial blood supply. This may be one explanation for the molecular myocardial changes, and may reflect a possible cause of "reverse remodelling".

The focus of this special issue of "Molecular and Cellular Biochemistry" is the underlying mechanisms that regulate cardiac growth. The new information provided in the issue can be utilized to design new treatment modalities that will reduce the incidence of cardiac failure, which will improve quality of life in patients with chronic heart disease.

Understanding the pathophysiology; cellular mechanisms of disease progression; different risk factors for cardiovascular disease; dietary effects on cardiovascular health and cultural differences are as important as dealing with the economic burden of cardiovascular mortality and morbidity. "Frontiers in Cardiovascular Health" discusses the factors that lead to cardiovascular death and strategies for their prevention from molecule to population.

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.

Over two centuries ago, oxygen was discovered as "air vital": the component of the earth's atmosphere necessary for life. The deleterious ef­ fects of oxygen radicals and activated oxygen species on a variety of biological systems have now been described.

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

It has been known or suspected for centuries that there is an association between mind and emotions and the occurrence of heart disease apd sudden death. During the past fifty years this relationship has become identified with the concept of Stress, a notion developed and popularized by Hans Selye. In recent years there has been an upward surge of interest in stress by scientists in several disciplines and by the general public. Although, books, journal articles, seminars and media programs devoted to stress now abound, the definition, manifestations, mechanisms, and management of stress remain uncertain and controversial. In an attempt to clarify the situation an International Symposium on Stress and Heart Disease was held in Winnipeg, Canada, June 26-29, 1984, and the proceedings form the basis of this book and its companion volume "Patho­ genesis of Stress-Induced Heart Disease". Although most species which have ever existed are now extinct through countless millenia, the human species has successfully adapted to changing conditions ("stressors") such as ice ages, predators and parasites, wars, famine and plague, and now it is coping with rapidly changing social, economic and political circumstances. Such adaptation occurs at all levels of life- at the molecular level within the cell, at the level of the whole cell, in the groups of cells as organs, in the entire organism or individual, and in some cases, in the society in which the individual lives.

The focus of this special issue of Molecular and Cellular Biochemistry is underlying mechanisms that regulate cardiac growth.

The World Heart Congress with a focus on "Frontiers in Cardiovascular Health" held in Winnipeg during July 6-11, 2001, made a unique attempt to bring these specialists together to brainstorm and map out the course of action for cardiovascular research and health in the next century.

Cellular signaling in cardiac muscle refers to the myriad of stimuli and responses that direct and control the physiological operation of this organ. Our understand­ ing of these complex signaling cascades has increased dramatically over the past few decades with the advent of molecular tools for their dissection. Moreover, this infor­ mation is beginning to provide tangible targets towards manipulating cardiac func­ tion in the setting of cardiovascular disease. The mechanisms and factors that regulate cardiac cell growth are of particular interest as both adaptive and maladaptive responses can occur during cardiac hypertrophy. Cardiac hypertrophy describes the increase in individual cardiac myocyte size that is accomplished through the series and/or parallel addition of sarcomeres. The ability of cardiac muscle to increase in size through hyperplasia becomes highly restricted or negligible shortly after birth. Consequently, the increase in heart size associated with development and growth of an individual occurs through hypertrophy. In response to a chronic increase in workload, cardiac muscle cells can dramatically increase in size to face their increasing contractile demands. While this plasticity is clearly a ben­ eficial response under many conditions, it can be highly deleterious and inappropri­ ate under others. For example, cardiac hypertrophy associated with endurance exercise clearly enhances athletic performance. In contrast, the hypertrophy associated with chronic hypertension, stenotic or regurgitant heart valves, or following a myocardial infarction often continues far beyond the period where this adaptive response is ben­ eficial.

The Frontiers in Cardiovascular Health varies between and within nations, depend­ ing upon the level at which the battle is fought for better cardiovascular health. According to the 1997 World Health Report, 15 million deaths (i. e. 30% of the total number of deaths) were attributable to cardiovascular diseases and this number is on the rise. The projection for the year 2020 is quite alarming with an expected cardiovascular mortality reaching 50 million. Much of this burden is projected to occur in developing countries, more specifically in the most populous countries of the world, namely China and India. These countries are already burdened with infectious and parasitic diseases and are trying to eradicate such diseases. With increasing life expectancies people all over the world, especially in developing coun­ tries, are exposed to degenerative atherosclerosis resulting in increased cardiovascu­ lar mortality and morbidity. In developing countries, resources available for health care are very limited. For example many of the African countries spend less than $10 per person per year on his/her entire health care let alone cardiovascular health. The average health care budget for nearly two thirds of the global population is well below $100 per year, on a per capita basis. Therefore, in developing countries health promotion and primary prevention are the frontiers by necessity. Improving awareness and health education is not only a matter of choice but is an absolute necessity.

Diabetes and cardiovascular disease together account for the largest portion of health care spending compared to all other diseases in Western society. This work seeks to provide an understanding of the causes of diabetes and its cardiovascular complications. As this understanding becomes more widely appreciated, it will serve as a foundation for evidence-based care and wider acceptance of sound science. The International Conference on Diabetes and Cardiovascular Disease, held in Winnipeg, in June 1999, was organized to bring together a multi-disciplinary group of researchers dedicated to further knowledge amongst researchers, care givers, and the managers of the health system. The invited speakers submitted their works for publication, which serves as the basis for this book. Major themes include: epidemiology of diabetes mellitus, metabolic risk factors in diabetes and cardiovascular disease, hypertension in diabetes mellitus, cardiac function in diabetes, glycemic control and improved cardiovascular function, diabetes management, and endothelial function in diabetes.

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