Whenever the heart is challenged with an increased work load for a prolonged period, it responds by increasing its muscle mass--a phenomenon known as cardiac hypertrophy. Although cardiac hypertrophy is commonly seen under physiological conditions such as development and exercise, a wide variety of pathological situa tions such as hypertension (pressure overload), valvular defects (volume overload), myocardial infarction (muscle loss), and cardiomyopathy (muscle disease) are also known to result in cardiac hypertrophy. Various hormones such as catecholamines, thyroid hormones, angiotensin II, endothelin, and growth factors have also been shown to induce cardiac hypertrophy. Although the exact mechanisms underlying or pathological forrns of cardiac hypertrophy are poorly under the physiological stood, an increase in the intraventricular pressure is believed to represent the major stimulus for the development of cardiac hypertrophy. In this regard, stretching of the cardiac muscle has been shown to induce the hypertrophic response, but the role of metabolic influences in this process cannot be ruled out. Furthermore, different hormones and other interventions in the absence of stretch have been observed to stimulate protein synthesis in both isolated cardiomyocyte and vascular myocyte preparations. Nonetheless, it is becoming dear that receptor as well as phospholipid linked signal transduction pathways are activated in some specific manner depend ing upon the initial hypertrophic stimulus, and these then result in an increase in the size and mass of cardiomyocytes.

These Proceedings are from the Fifth Annual Meeting of the American Section of the International Society for Heart Research held at Hilton Head Island, South Carolina, September 21-24, 1983. The program and abstracts were published in the Journal of Molecular and Cellular Cardiology, Vol. 15, Supplement 4, September 1983, Academic Press. This Symposium Proceedings consists of three sections. Section I deals with the mechanical factors and their i'nfluence on coronary blood flow in the normal and failing heart. Section II is developed around the area of vascular smooth muscle and the factors that may control it which ultimately play such an important role in the regulation of coronary blood flow. Section III is primarily devoted to the mechanical aspects of the function of the heart in both hypertrophy and failure including the molecular changes in the myocyte, alterations in neural control, and in inotropic responsiveness of the hypertrophied and failing heart. The editors hope that these three areas encompass a significant body of new and ongoing information that will be helpful to those who work in these areas as well as those who treat patients with varying degrees of myocardial failure or with compromised coronary circulations. The editors express their appreciation to all the contributors and to Ms. Jeri B. McClain for assisting in the organization and compiling of this volume. Francis L. Abel, M. D. , Ph. D. Walter H. Newman, Ph. D.

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.

The Stressed Heart is truly unique in concept and will provide an eXCItmg adventure to the reader no matter what his or her field of expertise and interest. The title, although quite appropriate, does not adequately indicate the range of topics considered or the rational interrelationships among them. Indeed, perhaps the most important point to be learned from the book is that a serious consideration of the response of the heart to mechanical overload, ischemia, or excessive humoral stimuli must include evaluation of each of the topics in the table of contents. The heart responds to stress through alterations in both structure and function. How these changes are brought about is the subject of the initial chapters. These consider first the normal regulation of gene expression in the heart, the rapid response to mechanical overload that leads to both quantitative and qualitative changes in the contractile proteins, and our current understand ing of the signals that might be elicited by stress and alter gene expression. One chapter emphasizes the fact that, regardless of the nature of the stress, the common denominator is a discrepancy between energy requirements and expenditure. The central role of cellular acidosis in initiating the sequence of responses to stress and the possible roles of peptide regulators of transcription and protein regulators of translation are considered in detail.

Left ventricular hypertrophy (LVH) is usually considered to be a compen satory adjustment of heart muscle to an inreased work load. LVH develops in the course of valvular or congenital heart disease, or when part of the myocardium is damaged by long-standing ischemia or infarction. In the hypertrophied heart the muscle fibers increase in size, not in number. The fibers are found to contain a larger number of myofibrils and the cell organelles are larger. From epidemiologic studies it is known that even mild LVH is associated with myocardial ischemia, ventricular arrhythmias, and sudden cardiac death. Most cases of LVH show focal degenerative tissue changes including cellular atrophy, myofibrillar disorganization, interstitial fibrosis, and loss of intracellular connections. Myocardial dysfunction develops and, unlike the functional adaptive changes found in pure hypertrophy, is not reversible by surgical treatment of the valvular heart disease or medical correction of hypertension. Interstitial fibrosis, intracellular changes of musc Ie cells, and loss of contract ile tissue lead to poor mechanical function and undoubtedly increase the risk of ischemia, arrhythmias, or sudden death, a well-recognized problem in patients with a variety of heart diseases. Even When successfully treated, the patients may remain at risk if the compensatory hypertrophy is not fully reversed. Epidemiologic studies conducted in the Framingham population in the early 1950' s demonstrated LVH according to electrocardiographic criteria in 1. 5% of the population; 2% of the population had LVH according to chest X-ray criteria.