Myocardial infarct size-Limiting effect of ischemic preconditioning: Its natural decay and the effect of repetitive preconditioning.

To characterize the cardioprotective effect of ischemic preconditioning, its natural decay and the effect of repetitive preconditioning were studied in the rabbit. Control rabbits underwent simple 30-minute coronary occlusion and 72 h reperfusion. In four groups, hearts were preconditioned with 5 minutes of ischemia and then allowed to "recover" for 5, 15, 25, or 35 minutes prior to the 30-minute coronary occlusion. In another two groups of rabbits, the preconditioning (PC) was performed by two or four cycles of 5 minutes ischemia separated by 5 minutes reperfusion. Infarct size was 43.9% ± 5.0% of area at risk in control rabbits. With recovery periods of 5 and 15 minutes, PC limited infarct size to 20.7% ± 2.9% and 26.7% ± 4.3% of the area at risk, respectively. As the recovery period increased, the infarct sizes progressively approached the control value, though PC still tended to be beneficial with a recovery time of 35 minutes. After two or four repetitions of 5-minute PC, infarct size was 16.4% ± 4.2% and 13.7% ± 2.6% of the area at risk, respectively, which were not significantly different from that after a single 5-minute PC (20.7% ± 2.9%). In another series of experiments, alteration of regional systolic thickening fraction (TF) after PC was assessed by an epicardial Doppler probe. Post-PC recovery of TF was 64.9% ± 8.9% of baseline value at 5 minutes and 73.2 ± 7.2% at 35 minutes after reperfusion, showing the persistence of modest stunning. These results suggest that in the rabbit heart, 5 minutes ischemia affords the myocardium a marked resistance against ischemic necrosis and that this resistance, which is unrelated to myocardial stunning, decays over a period of 30 minutes. Furthermore, the data imply that the resistance to ischemic injury is almost maximally induced by a single episode of 5 minutes ischemia and is not markedly enhanced by its repetition.