LEFT-VENTRICULAR REMODELING FOLLOWING EXPERIMENTAL MYOCARDIAL-INFARCTION

Experimental myocardial infarction is a model of cardiac overload in w hich part of the cardiac muscle is removed. The resulting left ventric ular insufficiency depends on the size of the infarct and time. The in farcted area remodels, due to proteolytic activity of inflammatory cel ls and collagenogenesis from fibroblast activity. The phenotype of the residual healthy cardiac muscle undergoes modification, and there are peripheral vascular changes which are partly dependent on the activat ion of pressor systems and/or inactivation of dilator systems. The cha nges are proportional to the infarct size at any given time after indu ction of the model. The degree of right ventricular hypertrophy and th e drop in arterial pressure are upstream and downstream markers of the loss of left ventricular function and therefore indicate the extent o f the remodelling. The increase in type V-3 isomyosin, the amount of s ubendocardial collagen, and the biosynthesis, storage and secretion of atrial natriuretic factor (ANF) are all proportional to the infarct s ize and the degree ee of cardiac overload. The level of urinary cGMP i s also correlated with infarct size. These indices show ventricular re modelling, increased stress and energy restriction of the residual hea lthy cardiac muscle The activation of peripheral pressor systems also depends on infarct size. They reflect the influence of defective cardi ac pumping on the kidney, liver, brain and endothelium. Massive infarc ts are accompanied by an increase in circulating renin and in renal re nin content, by a decrease in angiotensinogen due to its consumption b y venin, and to its insufficient hepatic synthesis, and by an increase in vasopressin secretion and biosynthesis in the hypothalamus. Conver ting enzyme inhibition has a beneficial effect in this model by loweri ng cardiac load. It reduces arterial pressure, reverses bi-atrial and right ventricular hypertrophy, I educes the changes in the myosin isoe nzyme patterns and normalizes subendocardial fibrosis and the level of ANF. Although the effects of converting enzyme inhibition are benefic ial in this model, they are restricted by their inability to normalize the load and stress when the initial loss of cardiac contractile mate rial exceeds 40%.