Effect of repeated regional myocardial ischemia in the rat heart on reperfusion arrhythmias and release of norepinephrine.

We tested the hypothesis that repetitive regional myocardial ischemia in the rat could decrease reperfusion ventricular arrhythmias, possibly acting by diminished release of norepinephrine. Isolated perfused working rat hearts were pre-labeled with tritiated norepinephrine (NE3H). The efflux of 3H-labeled compounds was measured in the effluent coronary flow. Each heart was subjected to two consecutive periods of regional myocardial ischemia induced by ligature of the left coronary artery. The duration of the first ischemic period was 5 or 10 min and that of the second was 10 min. Serious rhythm disturbances did not occur during the first period of ischemia but did after reperfusion. The amount of NE3H liberated during the reperfusion period was more marked after an initial ischemic period of 10 min than after 5 min of ischemia. Reperfusion arrhythmias were of little importance after 5 min of ischemia but developed in a sustained pattern when reperfusion followed 10 min of ischemia. After 5 min of ischemia, the mean duration of reperfusion arrhythmias was 12.8 +/- 10.4 s during the first 3 min of reperfusion, but after 10 min of ischemia the mean duration of serious rhythm disturbances was 149.7 +/- 16.7 s. Reperfusion after the second 10-min occlusion increased the release of NE3H. In series 5-10, the percentage of NE3H compared with the total radioactivity was a mean of 71.4 +/- 3.3% during the 5 min of ligature, 79.0 +/- 5.3% during the first 3 min of reperfusion. During the 10-10 series in which the ligature was maintained for 10 min, the percentage of NE3H compared with the total radioactivity was 70.6 +/- 5.1%, 81.1 +/- 8.7% during the first 3 min of reperfusion. These results show no reduction of any catecholamine release or of reperfusion arrhythmias by repetitive regional ischemia and provide no evidence for any preconditioning effect after short periods of regional ischemia. The antiarrhythmic effects of repetitive myocardial ischemia such as preconditioning previously reported may depend on the exact protocols used.