Hypoxic reperfusion after brief ischemia potentiates ischemic preconditioning in isolated rat hearts

Ischemic preconditioning renders the myocardium resistant to a subsequent sustained ischemic insult. The aim of this study was to investigate whether the reoxygenation that occurs during the intervening reperfusion of ischemic preconditioning is required for the development of cardioprotection. Isolated perfused rat hearts were either non-preconditioned (CONT) or preconditioned by 5 min ischemia and 5 min normoxic (IPCN) or hypoxic (IPCH) reperfusion before being subjected to 30min total global normothermic ischemia followed by 30min normoxic reperfusion. IPCN did not significantly alter the pre-ischemic status of tissue metabolites. However, after IPCH,ATP and glycogen levels were depressed and lactate content increased. As expected, IPCN protected the myocardium in terms of post-ischemic functional recovery (LVDP: IPCN = 53 +/- 3% vs CONT = 31 +/- 4%; p < 0.01). IPCH also improved contractile recovery (LVDP: 71 +/- 5%, p < 0.01 vs CONT) and its cardioprotective effect was higher than that of IPCN (p < 0.05). At the end of reperfusion, tissue metabolite levels were not significantly different between IPCN and CONT groups while in IPCH group ATP level was significantly higher and AMP level was lower (p < 0.05 vs CONT). Our results show that i) during the intervening reperfusion of ischemic preconditioning, reoxygenation is not mandatory to achieve cardioprotection, and ii) a transient hypoxic reperfusion further enhances the beneficial effects of preconditioning against post-ischemic contractile dysfunction. We suggest that this latter phenomenon might be, at least in part, the consequence of glycogen depletion induced by the transient hypoxic reperfusion.