title: Remote ischemic preconditioning for myocardial protection: update on mechanisms and clinical relevance.
abstract: Ischemic heart disease is the leading cause of death for both men and women worldwide, accruing 7.4 million deaths in 2012. There has been a continued search for better cardioprotective modalities that would reduce myocardial ischemia-reperfusion injury. Among these attempts, a more convenient model of ischemic preconditioning, known as remote ischemic preconditioning (RIPC) was first introduced in 1993 by Przyklenk and colleagues who reported that brief regional occlusion-reperfusion episodes in one vascular bed of the heart render protection to remote myocardial tissue. Subsequently, major advances in myocardial RIPC came with the use of skeletal muscle as the ischemic stimulus. To date, numerous studies have revealed that RIPC applied to the kidney, liver, mesentery, and skeletal muscle, have all exhibited cardioprotective effects. The main purpose of this review article is to summarize the new advances in understanding the molecular mechanisms of RIPC during the past 5 years, including those related to capsaicin-activated C sensory fibers, hypoxia-inducible factor 1α, connexin 43, extracellular vesicles, microRNA-144, microRNA-1, and nitrite. In addition, we have discussed results from several recent human clinical trials with RIPC. Taken together, the emerging clinical evidence supports the concept that the effectiveness of RIPC paired with its low-cost and non-invasive features makes it an ideal treatment before reperfusion after sustained ischemia. More carefully designed studies are warranted to fully exploit the clinical benefits of RIPC and its potential implications in patients with cardiovascular disease.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University, Box 980204, 1101 East Marshall Street, Room 7-020D, Richmond, VA, 23298-0204, USA.
authors.forename: Rabia
authors.initials: R
authors.lastname: Gill
authors.forename: Robin
authors.initials: R
authors.lastname: Kuriakose
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Gertz
authors.forename: Fadi N
authors.initials: FN
authors.lastname: Salloum
authors.forename: Lei
authors.initials: L
authors.lastname: Xi
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Kukreja
mesh_terms: D000818:Animals; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D018482:Muscle, Skeletal / Q000098:blood supply; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D057170:Translational Research, Biomedical