Time-Related Normalization of Maximal Coronary Flow in Isolated Perfused Hearts of Rats With Myocardial Infarction

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Abstract
Background In the present study, we investigated the time dependency and regional differences of the vascular adaptation of the myocardium after myocardial infarction (MI) in rats. Methods and Results MI was induced by total occlusion of the left anterior descending coronary artery. Time-dependent adaptation of the coronary vasculature was determined by histological staining of endothelial cells and measurement of basal and maximal coronary flow at days 0, 4, 7, 21, 35, and 90 after surgery in isolated retrogradely perfused hearts of sham-operated and infarcted rats. Cardiac function was determined during anterograde perfusion. In a separate group of experiments, regional myocardial flow was measured with radiolabeled microspheres in sham-operated and infarcted hearts to determine local differences in adaptation. Basal coronary flow was completely normalized within 7 days, whereas maximal coronary flow was not normalized until 35 days after MI. Normal growth, as observed in sham-operated hearts, resulted in a parallel increase in coronary flow and tissue mass from day 7 to 35 after surgery. In contrast, the increase in coronary flow was lower than the hypertrophic response in the right ventricles and septa of infarcted hearts, whereas a parallel increase in tissue mass and coronary flow was observed in the left ventricles of these hearts. These functional data were supported by structural data that showed the presence of numerous and dilated vessels, especially in the border zone of the infarcted and noninfarcted tissue. Conclusions These observations demonstrate that vessel growth, predominantly in the region adjacent to the infarcted zone, results in complete normalization of coronary vasodilatory capacity within 35 days after MI.