Abstract 233: Cardioprotection with Postconditioning is Enhanced by the Late Phase of Ischemic Preconditioning via a COX-2-Mediated Mechanism in Conscious Rats
Background: Previous studies have shown that postconditioning (PostC) does not significantly reduce infarct size after coronary occlusion >45 min in rats and that the myocardial protection induced by PostC is not enhanced by the early phase of preconditioning (PC). We sought to determine whether PostC-induced protection is enhanced by the late phase of PC.
Methods: Conscious, chronically instrumented rats were assigned to a 45-min (Subset 1) or 60-min (Subset 2) coronary occlusion (O) followed by 24 h of reperfusion (R). In each subset, rats received no further intervention (control), were preconditioned with 12 cycles of 2-min O/2-min R 24 h before O (late PC), were postconditioned with 20 cycles of 10-s O/10-s R at the onset of R following O (PostC), or received PC+PostC without or with pretreatment with the COX-2 inhibitor celecoxib (3 mg/kg, ip) 10 min before PostC.
Results: Late PC alone reduced infarct size (tetrazolium) in subset 1 but not in subset 2 (Table⇓). PostC alone did not reduce infarct size in either subset. However, late PC+PostC resulted in robust infarct size reduction in both subsets, suggesting either an additive or a synergic effect of these two interventions on cardioprotection. COX-2 inhibition completely abrogated the infarct-sparing effect of PC+PostC in both subsets.
Conclusions: PostC can reduce infarct size after occlusions >45 min provided that PC is implemented 24 h earlier. Thus, unlike early PC, late PC enhances the cardioprotection induced by PostC, establishing another pathophysiological difference between the two phases of PC. The mechanism responsible for the additive/synergistic cardioprotective effects of late PC and PostC involves COX-2 activation.