EFFECTS OF ACUTE CORONARY OCCLUSION ON REMOTE MYOCARDIUM

At the time of an acute coronary artery occlusion, the behavior of myocardium "remote" from the distribution of the acutely occluded vessel is critical. This myocardial region must compensate for ischemic dysfunction in the zone of the occluded vessel. Some experimental animal data have shown anatomic and biochemical alteration in "remote" myocardium even when supplied by normal coronary arteries. Clinical studies have shown that when "remote" myocardium is supplied by stenosed vessels, it may demonstrate marked asynergy at the time of acute occlusion of another artery. The aims of the research plan are (1) to assess myocardial perfusion and wall thickening in "remote" myocardium supplied by a critically stenosed circumflex artery when the left anterior descending artery is suddenly occluded; (2) to determine the cause of any alterations observed in perfusion in or function of "remote" myocardium; (3) to assess infarct/risk ratio when the left anterior descending is occluded in the presence of a circumflex stenosis. Regional blood flow will be assessed by using radiolabeled microspheres, and wall thickening will be determined by using sonomicrometer crystals. Regional wall thickening and myocardial perfusion will be assessed during hypotension, during sympathetic stimulation, and in he setting of enhanced collateral development. These studies will be performed in anesthetized open-chested dogs. Infarct/risk ratios will be determined in awake dogs with enhanced collateral development. The hypothesis to be tested is that "remote" wall thickening and perfusion do not increase appropriately, or even decrease, in the setting of an acute left anterior descending occlusion and a critical circumflex stenosis. We hypothetize that these alterations are related to hemodynamic factors, the magnitude of collateral development, and to inappropriately high sympathetic discharge. We also hypothetize that the size of the infarct/risk ratio will be greater when the left anterior descending is occluded in the setting of a critical circumflex stenosis. Many patients who experience acute myocardial infarction have underlying multivesse disease. The experimental protocols described in this proposal are intended to give us a better understanding of the pathophysiological alterations that occur in this setting.