Studies will be carried out in animals with acute and chronic myocardial ischemia and infarction, to investigate mechanisms contributing to ischemic dysfunction of the left ventricle. The majority of studies will be carried out in intact conscious dogs with implanted coronary occluders, pressure catheters, and ultrasonic segment length transducers. In acute studies lasting up to one week, we will evaluate systolic properties of ischemic myocardium, including differential effects of ischemia upon left ventricular subendocardial and subepicardial segmental function and flow (radioactive microspheres), the mechanism of production of clockwise (nonworking) pressure-length loops in the ischemic segment, the mechanism of the postextrasystolic potentiation response in ischemic segments, and, using echocardiographic techniques, measurements of wall stress in the ischemic zone. We will also study diastolic properties of acutely ischemic myocardium, incuding the mechanism of """"""""creep"""""""" in ischemic segments, and the mechanism for decreases in compliance during reperfusion injury. We will also investigate chronic myocardial ischemia and infarction produced by abrupt coronary occlusion and by progressive coronary stenosis using implanted ameroid constrictors. The mechanical performance and flow of the myocardium in the collateral-dependent ischemic zone will be measured and compared in these two preparations. In addition, we will employ the progressive coronary stenosis model to determine whether exercise training can improve collateral conductance in the ischemic zone.
