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, microRNA-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.

Mitochondrial and Contractile Function of Human Right Atrial Tissue in Response to Remote Ischemic Conditioning

“…Protection by remote ischemic conditioning has been confirmed in all species tested so far 1. Remote ischemic conditioning by repetitive limb ischemia/reperfusion also reduces myocardial damage in patients undergoing elective interventional2 or surgical coronary revascularization3, 4, 5, 6 and in those with reperfused acute myocardial infarction 7, 8, 9, 10, 11, 12, 13.…”

Protection of coronary circulation: Evaluation by PET perfusion imaging

“…The ability to produce the protective effect by simply inflating a blood pressure cuff placed on the upper arm or thigh inducing periods of ischemiareperfusion has been important for its translation to the clinical setting. 1,2 In proof-of-concept clinical studies, RIC reduced myocardial infarct (MI) size assessed by cardiac enzymes, single-photon emission computed tomography (SPECT) perfusion imaging, or cardiac magnetic resonance (CMR) imaging by 20% to 30% when applied as an adjunct to primary percutaneous coronary intervention (PCI) or thrombolysis in patients with acute MI. 1,3 The effect of RIC on long-term clinical outcomes is currently being evaluated in acute MI patients in the Effect of Remote Ischemic Conditioning Before Hospital Admission (CONDI) trial.…”

“…1,2 In proof-of-concept clinical studies, RIC reduced myocardial infarct (MI) size assessed by cardiac enzymes, single-photon emission computed tomography (SPECT) perfusion imaging, or cardiac magnetic resonance (CMR) imaging by 20% to 30% when applied as an adjunct to primary percutaneous coronary intervention (PCI) or thrombolysis in patients with acute MI. 1,3 The effect of RIC on long-term clinical outcomes is currently being evaluated in acute MI patients in the Effect of Remote Ischemic Conditioning Before Hospital Admission (CONDI) trial. 4 The coronary vasculature has been considered as a target of RIC in addition to direct effect on the myocardium.…”

“…5 Mechanisms of RIC can be briefly summarized as activation of nociceptive fibers during brief, local injury that releases an unidentified molecule into the circulation and/or signal through the spinal cord to activate both cardiac vagal and sympathetic efferent neurons to release cardioprotective substances. 1 Many endogenously derived preconditioning agents are vasoactive (e.g., adenosine, nitric oxide, and bradykinin). Thus, it has been hypothesized that RIC can improve vascular function.…”

“…Studies have shown that RIC prevents peripheral endothelial dysfunction associated with ischemia, 1,2 but the effects on coronary blood flow have been controversial. 1,5 In an experimental model, repeated transient limb ischaemia lead to reduced coronary resistance and increased basal flow in the left anterior descending coronary artery in healthy pigs. 6 Similarly, basal blood flow velocity in the left anterior descending coronary artery assessed by transthoracic Doppler echocardiography was increased shortly after RIC in healthy human subjects.…”