A standard ischemic preconditioning (IPC) stimulus of one or more brief episodes of non-lethal myocardial ischemia and reperfusion elicits a bi-phasic pattern of cardioprotection. The first phase manifests almost immediately following the IPC stimulus and lasts for 1–2 h, after which its effect disappears (termed classical or early IPC). The second phase of cardioprotection appears 12–24 h later and lasts for 48–72 h (termed the Second Window of Protection [SWOP] or delayed or late IPC). The cardioprotection conferred by delayed IPC is robust and ubiquitous but is not as powerful as early IPC. Although there are some similarities in the mechanisms underlying early and delayed IPC, one of the major distinctions between the two is the latter’s requirement for de novo protein synthesis of distal mediators such as iNOS and COX-2 which mediate the cardioprotection 24 h after the IPC stimulus. The phenomenon of delayed IPC has been demonstrated in man using a variety of experimental models. However, its clinical application has been limited by the same factors which affect early IPC- i.e. the need to intervene before the onset of myocardial ischemia, thereby restricting its potential clinical utility to planned settings of acute myocardial ischemia-reperfusion injury such as coronary artery bypass graft surgery, cardiac transplantation and percutaneous coronary intervention. In this article, the focus will be on the origins of delayed IPC, the mechanisms underlying its delayed cardioprotective effect, and the potential areas for its clinical application.
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