There are numerous reviews on the signal transduction of the conditioning phenomena, and some of them are excellent, so why this one now? The present review attempts to (1) briefly summarize and update the existing knowledge, and such update is practically useful from time to time, (2) focus on novel and emerging signaling modules, (3) identify potential common signaling patterns for the conditioning phenomena that are robust, translatable, and therefore potential drug targets, and (4) highlight failure and success in the translation of signaling events from reductionist experimental preparations and models to humans with ischemic heart disease (IHD) and suggest future strategies. Although the translation of ischemic postconditioning and remote ischemic conditioning protocols to patients with acute myocardial infarction has been fairly successful, the pharmacological recruitment of cardioprotective signaling has been largely disappointing to date. Cardioprotective signal transduction appears as a highly concerted spatiotemporal program. The present review characterizes the signal transduction underlying the conditioning phenomena, including their physical and chemical triggers, intracellular signal transduction, and effector mechanisms, notably in the mitochondria. Even ischemia/reperfusion in organs remote from the heart provides cardioprotection (remote ischemic conditioning).

The conditioning phenomena provide such cardioprotection, insofar as brief episodes of coronary occlusion/reperfusion preceding (ischemic preconditioning) or following (ischemic postconditioning) sustained myocardial ischemia with reperfusion reduce infarct size. Therefore, cardioprotection beyond that by timely reperfusion is needed to reduce infarct size and improve the prognosis of patients with acute myocardial infarction. Reperfusion is mandatory to salvage ischemic myocardium from infarction, but reperfusion per se contributes to injury and ultimate infarct size. Customer Service and Ordering Information.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).

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