ISCHEMIC PRECONDITIONING - TIME-COURSE OF RENEWAL IN THE PIG

Objective: The aim was to examine whether ischaemic preconditioning can be renewed by a second cycle of brief coronary occlusions in pigs subjected to two different reperfusion intervals (1 h or 4 d). Methods: Ischaemic preconditioning was induced by a cycle of two 10 min occlusions of the left anterior descending coronary artery separated by 30 min of reperfusion. Infarction was induced with a subsequent 1 h occlusion and a 2 h reperfusion period. There were four experimental groups: in group I (n=5), a 30 min reperfusion was interposed after the preconditioning cycle prior to the sustained occlusion; in group II (n=5), this time frame was extended to 1 h; in group III (n=5), the preconditioning cycle was renewed 1 h after the first cycle; in group IV (n=5), the second cycle was performed 4 d later. Control pigs (n=5) were subjected to 1 h coronary occlusion and 2 h reperfusion without previous short occlusions. Infarct size was measured with p-nitro blue tetrazolium and was expressed as a percent of area at risk. Results: The percent of the risk region infarcted was 69.9(SEM 3.8)% for controls, 22.9(3.5)% in group I (p<0.001 v controls), 67.3(5.2)% in group II, 66.3(4.2)% in group III, and 17.9(3.9)% in group IV (p<0.001 v controls). Regional wall function measured with ultrasonic crystals deteriorated through the reperfusion intervals, indicating different underlying mechanisms for ischaemic preconditioning and myocardial stunning. Conclusions: Ischaemic preconditioning with two 10 min occlusions reduced infarct size resulting from a 60 min coronary occlusion when that was performed 30 min after the last short occlusion. This effect was lost after 1 h. Preconditioning could be renewed by a second cycle of brief coronary occlusion and reperfusion 4 d but not 1 h after the first cycle. These results suggest the release of a mediator from an exhaustible pool.