PRECONDITIONING WITH 15-MINUTE ISCHEMIA EXTENDS MYOCARDIAL INFARCT SIZE AFTER SUBSEQUENT 30-MINUTE ISCHEMIA IN RABBITS

Ischemic preconditioning (PC) induced by 1 cycle of 5-min coronary occ lusion and 5-min reperfusion Limits infarct size (IS) after 30-min sus tained ischemia in rabbits. The shortest ischemic period that induces the PC effect in rabbits is 3 min. To establish the maximum ischemic p eriod to induce a beneficial PC effect, we examined the effect of PC p eriods of 10 and 15 min on IS after sustained ischemia. The IS in cont rol rabbit hearts after 30 min of sustained occlusion of the left ante rolateral coronary artery and 48-h reperfusion was compared with that of hearts treated as follows before being subjected to PC: 5-min occlu sion and 5-min reperfusion; 10-min occlusion and 5-min reperfusion; or 15-min occlusion and 5-min reperfusion. In addition, the IS after 15- min or 45-min occlusion and 48-h reperfusion was measured. There was n o significant difference in blood pressure, heart rate, or area at ris k (AAR) among the rabbits in 5 groups. The IS measured histologically was 40+/-4% of AAR in the control, 10+/-3% after 5-min PC, and 12+/-2% after 10-min PC. However, in the 15-min PC group, the IS was 77+/-4% of AAR, which was significantly larger than that of the controls, but similar to that of hearts subjected to 45-min ischemia and reperfusion (67+/-3%). As 15 min of preconditioning ischemia alone caused small i nfarcts (18+/-1% of AAR), the infarcts caused by sustained ischemia pe r se in the 15-min PC group was estimated to be 72+/-5% of AAR, which was still significantly higher than in the control groups. We conclude that the maximum period of preconditioning ischemia that induces card ioprotection in rabbits is 10 min. When the ischemic period is longer than this, the IS after sustained ischemia is increased rather than re stricted. However, the infarcted size in the 15-min PC group was not h igher than that in the group subjected to 45-min continuous ischemia. This may be a major limitation for any clinical application of PC.