Adaptive and Pathological Alterations in Experimental Cardiac Hypertrophy

Abstract

Based on investigations of various models of experimental cardiac hypertrophy (renal hypertension, spontaneous hypertension, aortic stenosis, swimming training, thyrotoxicosis), an attempt has been made to characterize adaptive and pathological alterations that are inherent to or accompany the process of hypertrophy. In principle, the designation of a process as adaptive is rooted in a teleological point of view and implies that the basic tendency of the respective structural and functional alterations is appropriate for coping with the altered functional requirements. This does not mean, however, that such alterations are favorable under all conditions and in all stages of hypertrophy. Since organisms generally reveal relatively stereotypic reaction patterns, the terms “adaptive” and “pathological” are not mutually exclusive in the final analysis. In the chronically pressure-loaded ventricle, nearly all alterations are ambiguous (myocardial mass increase, prolongation of the action potential, overproportional increase of intracellular contractile material, decrease of myofibrillar ATPase activity). The altered ATPase activity, which is based on a shift in the isoenzyme pattern of myosin in the direction of isoenzyme V₃, is accompanied by a decrease in unloaded shortening velocity but an increase in the efficiency of tension development, as is reflected in reduced oxygen consumption (per wall stress and heart rate) of the whole heart under isovolumetric conditions. This change in the elementary contractile process and the myofibrillar ATPase activity need not be interpreted a priori as negative. However, the ability to adapt to other types of loading, e.g., physical exertion with corresponding increase in heart rate, is limited by the specialization for coping with enhanced pressure load. The term “overadaptation” should be reserved for stages and degrees of hypertrophy in which the negative effects of double-faced alterations predominate. Rapid, excessive increase in pressure loading, as well as long-term hemodynamic overloading, leads to degenerative alterations of the myocardium. At the level of the whole ventricle, structural dilatation results in a decreased cardiac efficiency. Fibrosis of the ventricular wall, the pathogenesis of which is not always unequivocal, is also a negative factor for mechanical performance. Since there are pronounced degrees of hypertrophy without connective tissue increase, e.g., in thyrotoxicosis, fibrosis and accompanying decreased distensibility of the myocardium apparently are not necessarily involved in the development of hypertrophy. Ischemically induced alterations stemming from vasculopathy should be distinguished from hypertrophy-induced changes. The adaptive alteration of the heart in swim-trained rats, which involves an increase in myofibrillar ATPase activity and a shift in the myosin isoenzyme pattern in the direction of V₁, leads to an increase in functional capacity at all levels and is in agreement with the generally accepted concept of contractility.