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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.
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.
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.
This special issue of Molecular and Cellular Biochemistry contains
original research articles and review papers which were invited
from the participants of a recent meeting organized to honour the
60th birthday of Naranjan S. Dhalla, Ph.D., M.D.(Hon.). The
meeting, organized by Drs. Morris Karmazyn (London), Grant Pierce
(Winnipeg) and Balwant Tuana (Ottawa), was held at the Best Western
Lakeside Inn in Kenora, Ontario, Canada on August 23-25, 1996. The
meeting was entitled The Cellular Basis of Cardiovascular Function
in Health and Disease. There were over 40 invited speakers from 15
different countries represented at the meeting, attended by over
280 people. Keynote lectures were presented by Drs. Norman Alpert
(Burlington, VT), Robert Jennings (Chapel Hill, NC), Makoto Nagano
(Tokyo, Japan), Howard Morgan (Danville, PA), John Solaro (Chicago,
IL) and Nobuskira Takeda (Tokyo, Japan). Dr. Henry Friesen,
President of the Medical Research Council of Canada, presented Dr.
Dhalla with a plaque at the banquet honouring his research
accomplishments over his distinguished career. Dr.Dhalla's
outstanding research achievements in understanding the subcellular
basis of cardiovascular disease were highlighted at the meeting.
One of the unique aspects of the meeting was the special effort
made by 39 former trainees of Dr. Dhalla to attend the meeting to
honour their mentor. The ex-students and trainees came from all
over Canada, the United States, Japan, Slovakia, Germany, the Czech
Republic, Estonia and the Netherlands. The meeting was judged to be
an overwhelming success in terms of the scientific content as well
as collaborative interactions initiated.
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.
The focus of this special issue of Molecular and Cellular
Biochemistry is underlying mechanisms that regulate cardiac growth.
The new information provided in this special 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.
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.
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.
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.
According to the World Health Report (2000 http:/ /www. who.
int/whr), of the 55 million deaths worldwide in 1999, more than 16
million were secondary to car diovascular complications. With the
prospect of world population increasing from the current level of 6
billion to 9 billion by the middle of this century, the burden of
cardiac disease is going to increase astronomically. Furthermore,
scientists are being challenged not only to reduce mortality, but
also to improve quality of life. Thus, more than ever,
intellectuals from different disciplines including biology,
sociology, informatics and health care have to join forces to meet
the mandate. 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. Anytime there is a
relative increase in the workload on the heart, there are adap tive
myocardial as well as humoral responses. When these adaptations or
remodel ing at the organ, subcellular or gene level, become
inadequate for a proper tissue perfusion, the condition of heart
failure ensues. Prevention of the factors leading to the relative
increase in workload as well as a better understanding of the adap
tive responses and their failure are some of the hopes to combat
the morbidity and mortality due to heart failure.
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."
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.
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 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."
According to the World Health Report (2000 http:/ /www. who.
int/whr), of the 55 million deaths worldwide in 1999, more than 16
million were secondary to car diovascular complications. With the
prospect of world population increasing from the current level of 6
billion to 9 billion by the middle of this century, the burden of
cardiac disease is going to increase astronomically. Furthermore,
scientists are being challenged not only to reduce mortality, but
also to improve quality of life. Thus, more than ever,
intellectuals from different disciplines including biology,
sociology, informatics and health care have to join forces to meet
the mandate. 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. Anytime there is a
relative increase in the workload on the heart, there are adap tive
myocardial as well as humoral responses. When these adaptations or
remodel ing at the organ, subcellular or gene level, become
inadequate for a proper tissue perfusion, the condition of heart
failure ensues. Prevention of the factors leading to the relative
increase in workload as well as a better understanding of the adap
tive responses and their failure are some of the hopes to combat
the morbidity and mortality due to heart failure.
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."
Ideal for students through to experimental biologists and health
professionals dealing with the benefits and the failures of
physiological and pathophysiological adaptations, this book dives
into the role of the continuously changing natural environment on
gene expression before relating back to modern day health
conditions. It relays how gene expression is known to be modified
by our (or by the modern) environment inclusive of factors such as
gravity, altitude, temperature, air quality, physical conditioning
as well as lifestyle, before applying this to how it impacts both
health and disease conditions such as cardiac ischemia and
cardiomyopathies, stroke, dementia, Alzheimer's, cancer, metal
toxicity, etc.
Of great value to experimental biologists as well as clinicians who
deal with a wide variety of disease conditions, this volume delves
into cell adaptions, providing an insight into the different
stresses and other potentially harmful conditions a cell can face.
Several chapters in this book cover new developments in our
understanding of the biology of adaptation at the molecular,
cellular, organ and whole body level, providing an understanding of
the science behind the process of such an adaptation and
highlighting it as the key to future therapies.
A concise, in-depth analysis of the status of the sympathetic
system in heart diseases
This book summarizes the functional status of the sympathetic
neural system in cardiological diseased states and highlights
aspects of sympathetic neural activity that are important to an
overall understanding of the pathophysiology process. Critical
reviews of methods for evaluating sympathetic activity are
discussed, existing data is closely scrutinized, and attempts are
made to delineate the factors derived from increased sympathetic
activity. The book provides a physiologically and clinically based
approach to the investigation of the involvement of catecholamines
in cardiovascular diseases, which makes it a valuable addition to
the reference collections of researchers, clinical scientists, and
graduate students.
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.
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