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

Abstract

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 β-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.