RIPC for multiorgan salvage in clinical settings: evolution of concept, evidences and mechanisms.

Ischemic preconditioning is an intrinsic process in which preconditioning ischemia (ischemia of shorter duration) protects the organs against the subsequent index ischemia (sustained ischemia). Remote ischemic preconditioning (RIPC) is an innovative treatment approach in which interspersed cycles of preconditioning ischemia followed by reperfusion to a remote organ (other than target organ) protect the target organ against index ischemia and reperfusion-induced injury. RIPC of various organs to provide multi-organ salvage became a successful approach in numerous species of animals. Consequently, the concept of RIPC evolved in clinical setups, and provided beneficial effects in alleviating ischemia-reperfusion-induced injury in various remote organs, including myocardium. Clinically, RIPC stimulus is generally delivered by inflating the blood pressure cuff tied on the upper arm 20 mm greater than the systolic blood pressure, rendering the forearm ischemic for 5 min, followed 5 min reperfusion by deflating the cuff. This cycle is repeated for 3-4 consecutive periods to precondition the tissue and improve the survival. The institution of RIPC is beneficial in mitigating myocardial injury in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, heart valve surgery, drug-eluting stent implantation, kidney transplantation, elective decompression surgery. The involvement of hypoxia inducible factor-1α (HIF-1α), ATP-sensitive potassium channels, signal transducer and activator of transcription (STAT), matrix metalloproteinases, O-linked ß-N-acetylglucosamine (O-GlcNAc) levels, autonomous nervous system in mediating RIPC-induced cardioprotective effects has been explored clinically. However, comprehensive studies are required to elucidate the other possible mechanisms responsible for producing multi-organ protection during RIPC.

Remote preconditioning-endocrine factors in organ protection against ischemic injury.

Cardiovascular disease is the leading cause of death in the United States and developing world. Experimental and clinical studies have demonstrated that a number of interventions including brief periods of ischemia or hypoxia and certain endogenous factors such as opioids, bradykinin, growth factors or pharmacological agents are capable of protecting the heart against post-ischemic contractile dysfunction, arrhythmias and myocardial infarction. This conventional cardioprotection occurs via an autocrine or paracrine action in which these protective factors are released from the heart to act upon itself. Over the last ten years, a growing body of evidence indicates that a brief ischemic insult on one organ releases endogenous factors that protect other organs against a prolonged ischemic insult. This phenomenon, termed remote preconditioning or preconditioning at a distance, implicates an endocrine action, and may involve humoral or neural-endocrine signaling. This review will summarize the endocrine factors identified and implicated in this inter-organ cytoprotection.