Previous studies in my laboratory have shown that pressure-induced left ventricular hypertrophy markedly alters the coronary circulation in animals and man. When dogs with renal hypertension and left ventricular hypertrophy are subjected to sudden coronary occlusion, the incidence of sudden death increases three-fold and infarct size increases substantially. If hypertension in this model is relieved prior to or at about the time of coronary occlusion, the incidence of sudden death returns to control and so does infarct size. The objectives of this proposal are to pursue further studies in this area. First, we plan to determine if the presence of renal hypertension and left ventricular hypertrophy alters the relationship between time of reperfusion and infarct size expressed as a percent of the area at risk. We postulate that left ventricular hypertrophy and hypertension may accelerate the rate at which necrosis progresses across the risk zone following sudden coronary occlusion. If this is so, interventions aimed at altering the course of infarction in the presence of hypertension and left ventricular hypertrophy will have to be implemented very early following coronary occlusion. Second, we plan to determine how time dependent are the salutatory effects of relief of hypertension in dogs with renal hypertension and left ventricular hypertrophy subjected to sudden coronary occlusion. Our previous studies have demonstrated that if the hypertension is relieved prior to or at about the time of coronary occlusion the course of the myocardial infarction can be favorably altered. Since patients almost never arrive at the medical facility soon enough to be treated within minutes of the time of the onset of coronary occlusion, it is important to determine how late any given therapeutic regimen can be implemented and still have salutatory effects. All studies will be pursued in chronically-instrumented awake animals with renal hypertension and left ventricular hypertrophy and appropriate controls. These studies should provide important new information concerning the interaction between hypertension, left ventricular hypertrophy and myocardial infarction.
