Pathophysiology and Morphology of Myocardial Cell Alterations [antikvár]

Editorial Foreword This book consists of two parts. The first part deals with those alterations in myocardial cell metabolism that seem to be decisive in the production of structural damage, and the second part is mainly concerned with the morphological manifestations of myocardial cell injury. The bipartition is primarily for practical reasons and for the differences in methodology. However, the basic research trends in most of these functional and morphological studies are convergent. In fact, during the last decade, much work has been carried out that demonstrates the striking interrelationship between metabolic disorders and structural decay. In putting together the most significant results about myocardial necrotization, this book presents a highly actual synopsis. Thus, it has become clear in recent years that myocardial high-energy phosphate exhaustion has to be considered as a common denominator in the production of various types of cardiac lesions, whatever the special reasons of a deficient high-energy phosphate balance may be. Obviously, phosphate-bond energy is required for a wide variety of synthetic reactions that are essential, even at rest, for the continuous regeneration of the myocardial cell. Therefore, severe structural damage occurs if the high-energy phosphate concentration drops below a critical level due to insufficient ATP synthesis in anoxia or ischemia or to exhaustive ATP consumption. For instance, cardiotoxic overdoses of ?!-adrenergic catecholamines waste ATP, which is necessary for the maintenance and survival of the myocardial cells, in useless mechanical reactions. Furthermore, it turned out that the deleterious action of ?!-adrenergic overstimulation isspecifically mediated by Ca. Physiologically, ?!-adrenergic catecholamines increase the transmembrane Ca influx into the excited myocardial fibers so that the Ca-dependent myofibrillar ATPase, as well as the Ca transport ATPase of sarcoplasmic reticulum and mitochondria, are more activated. However, with increasing doses of such catecholamines, Ca uptake and splitting of ATP may become so large that a dangerous fall in the ATP and CP concentrations occurs. In addition, the increase in intracellular Ca leads to functional and structural damage of the mitochondria so that their phosphorylating capacity declines. In other words, Ca ions destroy the myocardial fiber if their rate of influx becomes excessive. For instance, isoproterenol, introduced by Dr. Rona as a most useful tool for the production of experimental cardiac necroses, is particularly potent in causing Ca overload and high-energy phosphate depletion. On the other hand, isoproterenol-induced high-energy phosphate deficiency and cardiac lesions both can be prevented with the help of a new group of Ca-antago-nistic compounds that are capable of bringing back the transmembrane Ca uptake to an almost normal range. Interestingly enough, the well known cardioprotective action of K and Mg ions is also explainable on the basis of their natural Ca-antagonistic properties. Conversely, substances such as certain corticosteroids, dihydrotachysterol or NaH2P04, which sensitize the hearts for the production of necroses, exert their influence by means of an enormous potentiation of myocardial Ca incorporation. The present volume contains papers presented at the Sixth Annual Meeting of the International Study Group for Research in Cardiac Metabolism, jointly organized by the American and European Research Groups in Freiburg, Germany (September 25-28, 1973). As already noted in the Editorial Foreword to Volume 5, the meeting was sponsored by the Gesellschaft ftir Strahlen- und Umweltforschung, Munich. I wish to thank Professor R. Wittenzellner, Scientific xi