Remote ischemic conditioning: from bench to bedside

Abstract

Remote ischemic conditioning (RIC) is a therapeutic strategy for protecting organs or tissue against the detrimental effects of acute ischemia-reperfusion injury (IRI). It describes an endogenous phenomenon in which the application of one or more brief cycles of non-lethal ischemia and reperfusion to an organ or tissue protects a remote organ or tissue from a sustained episode of lethal IRI. Although RIC protection was first demonstrated to protect the heart against acute myocardial infarction, its beneficial effects are also seen in other organs (lung, liver, kidney, intestine, brain) and tissues (skeletal muscle) subjected to acute IRI. The recent discovery that RIC can be induced non-invasively by simply inflating and deflating a standard blood pressure cuff placed on the upper arm or leg, has facilitated its translation into the clinical setting, where it has been reported to be beneficial in a variety of cardiac scenarios. In this review article we provide an overview of RIC, the potential underlying mechanisms, and its potential as a novel therapeutic strategy for protecting the heart and other organs from acute IRI.

Keywords: ischemia-reperfusion injury; remote ischemic perconditioning; remote ischemic postconditioning; remote ischemic preconditioning.

Figure 1

The timing and the potential mechanisms underlying remote ischemic conditioning (RIC). The RIC stimulus can be applied prior to ischemia (preconditioning), after the onset of ischemia (perconditioning), or at the time of reperfusion (postconditioning). A variety of intracellular signaling mediators have been implicated in the protective effect of RIC. Three main mechanisms for transmitting the protective signal from the organ or tissue, in which the RIC stimulus is applied, to the target organ or tissue (these are not mutually exclusive): (1) neural pathway, (2) the release of circulating humoral factor(s), and (3) activation of a systemic protective effect (such as an anti-apoptotic or anti-inflammatory response).