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Remote ischemic pre-conditioning (rIPC) has emerged as a potential mechanism to reduce ischemia-reperfusion injury. Clinical data, however, have been mixed, and its physiological basis remains unclear, although it appears to involve release of circulating factor(s) and/or neural pathways. Here, the authors demonstrate that adenosine receptor activation is an important step in initiating human pre-conditioning; that pre-conditioning liberates circulating cardioprotective factor(s); and that exogenous adenosine infusion is able to recapitulate release of this factor. However, blockade of adenosine receptors in ischemic tissue does not block the protection afforded by pre-conditioning. These data have important implications for defining the physiology of human pre-conditioning and its translation to future clinical trials.

Original publication




Journal article


JACC Basic Transl Sci

Publication Date





461 - 471


ANOVA, analysis of variance, Ach, acetylcholine, FMD, flow-mediated dilation, GTN, glyceryltrinitrate, IR, ischemia-reperfusion, LV, left ventricular, NMD, nitrate-mediated dilation, adenosine, endothelium, ischemia, pre-conditioning, rIPC, remote ischemic pre-conditioning