ISCHEMIC PRECONDITIONING - TIME-COURSE OF RENEWAL IN THE PIG

Objective: The aim was to examine whether ischaemic preconditioning ca n be renewed by a second cycle of brief coronary occlusions in pigs su bjected to two different reperfusion intervals (1 h or 4 d). Methods: Ischaemic preconditioning was induced by a cycle of two 10 min occlusi ons of the left anterior descending coronary artery separated by 30 mi n of reperfusion. Infarction was induced with a subsequent 1 h occlusi on and a 2 h reperfusion period. There were four experimental groups: in group I (n=5), a 30 min reperfusion was interposed after the precon ditioning cycle prior to the sustained occlusion; in group II (n=5), t his time frame was extended to 1 h; in group III (n=5), the preconditi oning 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 subj ected to 1 h coronary occlusion and 2 h reperfusion without previous s hort occlusions. Infarct size was measured with p-nitro blue tetrazoli um and was expressed as a percent of area at risk. Results: The percen t 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). Regi onal wall function measured with ultrasonic crystals deteriorated thro ugh the reperfusion intervals, indicating different underlying mechani sms 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 perform ed 30 min after the last short occlusion. This effect was lost after 1 h. Preconditioning could be renewed by a second cycle of brief corona ry occlusion and reperfusion 4 d but not 1 h after the first cycle. Th ese results suggest the release of a mediator from an exhaustible pool .