IMPAIRED CARDIAC-FUNCTION IN RATS WITH HEALED MYOCARDIAL-INFARCTION -CELLULAR VS MYOCARDIAL MECHANISMS

The inotropic responsiveness of isolated perfused rat hearts and singl e left ventricular (LV) myocytes to extracellular Ca2+ ([Ca2+](0)) was examined 3 wk after ligation of left main coronary artery. Myocytes i solated from myocardial infarcted (MI) hearts were 10% longer. At [Ca2 +](0) of 1.1 mM, cell shortening as well as intracellular Ca2+ concent ration dynamics were similar between MI and sham LV myocytes. At [Ca2](0) of 4.9 mM, maximal extent of cell shortening was significantly le ss in MI myocytes (16 +/- 1 vs. 22 +/- 1%), and peak intracellular Ca2 + concentration was also substantially lower. Thus, under conditions o f high [Ca2+](0), decreased sarcolemmal Ca2+ influx and Ca2+ release d uring excitation-contraction may contribute to systolic dysfunction in MI hearts. Perfused working hearts and isovolumic heart preparations with infarcted LV displayed depressed maximal systolic pressure and de creased sensitivity to the inotropic effects of [Ca2+](0). Our data al so indicate that, in addition to possible abnormalities in the contrac tile response of single myocytes, global factors such as loss of funct ional myocar dium, altered chamber geometry, tissue fibrosis, andior s ubendocardial ischemia contributed to depressed LV function in post-MI hearts perfused at physiological [Ca2+](0).