Reperfusion of acute myocardial infarction 6-12 hours after coronary arterial occlusion (CAO) is associated with reduced expansion of the infarct and improved survival; reperfusion later than 12 hours provides no benefit and may increase the risk of cardiac rupture. This proposal tests two hypotheses: reperfusion 6 hours after (CAO) stiffens the infarct, increases collagen formation, reduces collagen degradation, attenuates left ventricular (LV) expansion and improves LV function. Reperfusion 24 hours after CAO impairs collagen formation, increases collagen degradation and does not improve LV geometry or function. The study involves serial measurements over 12 weeks in a sheep model of antero-apical infarction of 23 percent of LV mass that consistently evolves into an aneurysm and includes hemodynamic measurements of LV function; quantitative echocardiograms to document LV remodeling; biaxial stress extension measurements of infarcted myocardium; and measurements of collagen formation, alignment and degradation (in collaboration with Dr. Karl Weber, University of Missouri/Columbia). The data are expected to elucidate the mechanism of the effects of delayed (too late to rescue myocytes) reperfusion on acute myocardial infarctions.
