DELAYED-EFFECTS OF SUBLETHAL ISCHEMIA ON THE ACQUISITION OF TOLERANCE TO ISCHEMIA

The infarct-limiting effect of ischemic preconditioning is believed to be a transient phenomenon. We examined the delayed effects of repetitive brief ischemia on limiting infarct size in an open-chest dog model by an occlusion (90 minutes) of the left anterior descending coronary artery (LAD) followed by reperfusion (5 hours). The dogs were preconditioned with four brief repeated ischemic episodes induced by 5-minute LAD occlusions with subsequent reperfusion. The size of infarcts initiated by a sustained occlusion immediately or 24 hours after preconditioning was significantly smaller when compared with infarcts in sham-operated dogs (for the immediate occlusion, 14.4+/-2.0% versus 39.0+/-3.7%, respectively [p<0.01]; and for the delayed occlusion, 18.8+/-3.4% versus 35.1+/-4.6%, respectively [p<0.05]); however, when the infarction was induced 3 hours (31.2+/-3.7% versus 37.5+/-4.2%, respectively) or 12 hours (25.4+/-4.8% versus 35.0+/-5.3%, respectively) after repetitive ischemia, the infarct size did not differ. No differences were seen in regional myocardial blood flow or rate-pressure products between the two groups. These results indicate that an infarct-limiting effect of brief repeated ischemia can be observed 24 hours after sublethal preconditioning.