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.