Studies are proposed to examine myocardial function and coronary vascular reactivity following intervals of myocardial ischemia which result in prolonged systolic dysfunction without infarction. These studies will be performed in chronically instrumented dogs in which coronary artery blood flow is measured with electromagnetic flowmeters, left ventricular segment shortening and systolic wall thickening are assessed with ultrasonic microcrystals, and regional myocardial perfusion is measured with radio-labelled microspheres. Since in the clinical setting recurrent myocardial ischemia is most likely to occur when a coronary artery stenosis prevents an adequate increase in blood flow during exercise or other stress, myocardial and coronary vascular function will be characterized following intervals of ischemia produced by exercise in the presence of a flow-limiting coronary stenosis, as well as by brief repetitive episodes of total coronary artery occlusion. The effect of a persistent coronary stenosis which prevents hyperemia during the post-ischemic period, will be assessed. Repeated episodes of exercise-induced myocardial ischemia will be produced to determine whether cumulative abnormalities occur and demonstrate whether exercise stress may reveal subtle abnormalities of function which persist after recovery from post-ischemic dysfunction. The effect of calcium channel blockers on myocardial dysfunction during and following exercise in the presence of a coronary stenosis will be examined. Oxygen consumption of post-ischemic dysfunctional myocardium will be examined to determine whether metabolic requirements are decreased, and to establish whether the coupling between myocardial oxygen consumption and coronary blood flow are altered. Regulation of coronary blood flow will be examined to determine whether the post-ischemic period is associated with abnormalities of myocardial blood flow, coronary vascular reactivity or maximum coronary vasodilator capacity. Additional studies will determine whether alterations of coronary flow in post-ischemic myocardium results from a change in vascular responsiveness to adenosine, a reduction of adenosine production by the myocardium, or alteration of extravascular forces which act upon the intramural coronary vessels.
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