Hypoxia inducible factor 1 α as a mediator of ischemic preconditioning

The investigation of HIF-1 α mediated cardioprotection has been closely linked to ischemic preconditioning (IPC), an endogenous phenomenon, in which one or more brief episodes of non-lethal myocardial ischemia and reperfusion, protects the heart against a subsequent myocardial infarction. The IPC stimulus induces two distinct windows of protection, the “first window of protection” or “classical” IPC manifests immediately following the IPC stimulus and lasts up to 3–4 h, following which the protective effect wanes and re-appears 12–24 h later and lasting up to 72 h (termed the “Second Window Of Protection” [SWOP] or delayed IPC). The SWOP or delayed IPC requires the transcriptional activation of specific cardioprotective genes, raising the possibility that HIF-1 α may act as a mediator of delayed IPC to transcribe cardioprotective genes in this setting. As a result, many of the studies implicating HIF-1 α as a mediator of cardioprotection have used experimental models of SWOP or delayed IPC. However, more recent evidence suggests that HIF-1 α may also mediate the acute phase of IPC. Also ischemic postconditioning, an endogenous intervention in which reperfusion is interrupted by short-lived episodes of myocardial ischemia, has been reported to enhance HIF-1 α activity in adult rat hearts subjected to acute IR.