Remote ischemic conditioning

Abstract

In remote ischemic conditioning (RIC), brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue, or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical, or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microribonucleic acid-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting, and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible, and inexpensive.

Keywords: acute myocardial infarction; coronary artery bypass grafting; myocardial ischemia; reperfusion.

Figure

Central Illustration. Signal Transduction of Remote Ischemic Conditioning From the Source Organ in Response to Several Stimuli Via Neuronal and/or Humoral Transfer to the Heart and Other Organs, Where a Protective Intracellular Signal Transduction Cascade is Activated Akt = protein kinase B; Cx 43 = connexin 43; ERK = extracellular regulated kinase; eNOS = endothelial nitric oxide synthase; γPKC = protein kinase C γ; GSK3β = glycogen synthase kinase 3β; K_ATP = ATP-dependent potassium channel; mPTP = mitochondrial permeability transition pore; NO = nitric oxide; PI3-K = phosphoinositol-triphosphate kinase; RISK = reperfusion injury salvage kinase; SDF-1 α = stromal derived factor 1α.