The morphologic-functional correlative studies that we have carried out in the past 25 years with the various catecholamines have served as an example for analyzing myocardial reaction patterns and the reactions of the cardiac muscle cells to insult. These studies disclosed the unique nature of isoproterenol in producing 'infarct-like' myocardial necrosis. It appears that the pathogenesis of the catecholamine-induced myocardial necrosis is multifactorial. Our early studies suggested the role of relative hypoxia. Later studies by using extracellular fine structural protein tracers demonstrated the importance of microcirculatory effects as well as, in the norepinephrine model, that of early sarcolemmal membrane permeability alteration. The Ca2+ overload theory is supported not only by the experimental observations but also by its successful application in clinical cardiology. A new contribution is the recognition of catecholamine oxidation products in producing myocardial injury. Experimental data indicate that catecholamines play an important role in reperfusion and ischemic myocardial injuries. The sequence of events demonstrated by our studies with catecholamines might represent a common pathway in the evolution of myocardial changes in humans who develop myocardial lesions without narrowing or obstruction of coronary arteries. Investigation in the field of molecular and cellular cardiology has led to a better understanding of current clinical problems and helped to devise procedures for the prevention and management of human myocardial disorders. The isoproterenol-induced myocardial necrosis served as model to Professor A. Fleckenstein to formulate the Ca2+ overload theory of myocardial injury and develop a series of now widely used Ca2+ antagonistic drugs for the management and the prevention of human myocardial diseases.

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A spontaneous lesion of the islet of Langerhans characterized by fibrosis and enlargement is described in the aging albino rat, occurring almost exclusively in males. Further studies are in progress to define the histogenesis, endocrine aspect and functional significance of this lesion.

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