Failure of brief ischemic episodes to protect against myocardial dysfunction caused by ischemia and reperfusion in isolated rat hearts

Abstract

Brief periods of ischemia have been suggested to protect against myocardial injury caused by a subsequent episode of prolonged ischemia and reperfusion. However, the protective effects of brief ischemic periods against myocardial dysfunction after prolonged myocardial ischemia are controversial. To examine whether the protective effects of brief ischemic episodes relate to the extent of prior ischemic events, isolated rat hearts were subjected to either no preischemia (group A); one 5-minute episode of preischemia and 10 minutes of reperfusion (group B); or two 1-minute episodes of ischemia, each followed by 5 minutes of reperfusion (group C). All hearts were then subjected to 15 minutes of total ischemia and 10 minutes of reperfusion. In group A, after 10 min of reperfusion coronary perfusion pressure (CPP) was 31% ± 10% (mean ± SEM) higher than the control value, peak force of cardiac contraction (FCC) was 64% ± 5% lower, and heart rate was 18% ± 3% lower. In group B, CPP increased 26% ± 6%, FCC fell 58% ± 7%, and heart rate decreased 22% ± 8% (group B vs group A, P value not significant) after ischemia and reperfusion. In group C, CPP increased 23% ± 7%, FCC decreased 57% ± 8%, and heart rate fell 8% ± 4% on reperfusion (group C vs groups A and B, P value not significant). Creatine kinase (CK) was measured in the hearts from different groups and was found to be similar. Release of the adenosine triphosphate (ATP) metabolites hypoxanthine, inosine, and adenosine was also not different in the coronary effluents of the three groups of hearts. To determine whether brief ischemic periods would protect hearts subjected to a longer period of subsequent ischemia, additional groups of hearts were subjected to 25 minutes of ischemia and 20 minutes of reperfusion. Myocardial dysfunction after prolonged period of ischemia and reperfusion was also not affected by prior brief ischemic periods. Thus brief ischemic episodes of varying duration and frequency do not appear to protect against subsequent functional deterioration, CK loss, or release of ATP metabolites after prolonged ischemia (15 or 25 minutes) and reperfusion in the isolated rat heart.