Preconditioning at a distance: Involvement of endothelial vasoactive substances in cardioprotection against ischemia-reperfusion injury

There is growing preclinical as well as clinical evidence supporting remote ischemic preconditioning (RIPC), in which short cycles of non-fatal ischemia followed by reperfusion to an organ or tissue distant from the heart elicits cardioprotection. It is the most practical, non-invasive, cost-free, and clinically compatible, secure procedure for reducing ischemia-reperfusion induced injury. The use of a conventional blood pressure cuff on the upper or lower limb in eliciting cardioprotection has expedited its clinical applicability. Endothelium has been documented to respond very quickly to blood flow and hypoxia by releasing different humoral factors such as endothelium derived releasing factor, endothelium derived contracting factor, endothelium derived hyperpolarizing factor. In recent years, there have been studies suggesting the key role of endothelial derived factors in RIPC induced cardioprotection. The signaling cascade involves nitric oxide, gap junctions, epoxyeicosatrienoic (EETs) acids, Ca-activated K+ channels, angiotensin II, thromboxane A(2), superoxide anions and prostacyclin. The present review describes the role of these endothelial derived factors in RIPC induced cardioprotection with possible mechanisms. (C) 2016 Elsevier Inc. All rights reserved.