Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans : Role of the autonomic nervous system

• Published in: Journal of the American College of Cardiology Vol. 46; no. 3; pp. 450 - 456
• Main Authors: LOUKOGEORGAKIS, Stavros P, PANAGIOTIDOU, Anna T, BROADHEAD, Michael W, DONALD, Ann, DEANFIELD, John E, MACALLISTER, Raymond J
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 02.08.2005; Elsevier Limited
• Subjects: Adult; Analysis of Variance; Biological and medical sciences; Blood Flow Velocity; Cardiology; Cardiology. Vascular system; Cohort Studies; Coronary vessels; Endothelium, Vascular - physiopathology; Female; Follow-Up Studies; Forearm - blood supply; Heart attacks; Humans; Ischemic Preconditioning - methods; Kinases; Male; Medical sciences; Middle Aged; Primary Prevention - methods; Probability; Reference Values; Reperfusion Injury - prevention & control; Risk Assessment; Rodents; Time Factors; Human; Late; Reperfusion; Ischemia; Autonomic nervous system; Cardiovascular disease; Early; Circulatory system; Cardiology; Phlebology; Protection; Preconditioning
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2005.04.044

The aim of this study was to characterize the time course and neuronal mechanism of remote ischemic preconditioning (RIPC) of the vasculature in humans. Non-lethal ischemia of internal organs induces local (ischemic preconditioning) and systemic (RIPC) resistance to lethal ischemia-reperfusion (IR) injury. Experimental RIPC has two temporal components, is neuronally mediated, is induced by limb ischemia, and reduces infarct size. In humans, RIPC prevents IR-induced vascular injury. Determining the time course and mechanism is a prelude to clinical outcome studies of RIPC. Endothelial IR injury was induced by arm ischemia (20 min) and reperfusion, and measured by flow-mediated dilation. To establish if there are early and late phases, RIPC (three 5-min cycles of ischemia of the contralateral arm) was applied immediately, 4, 24, and 48 h before IR. To determine neuronal involvement, trimetaphan (autonomic ganglion blocker; 1 to 6 mg/min intravenous) was infused during the application of the RIPC stimulus. Flow-mediated dilation was reduced by IR (8.7 +/- 1.1% before IR, 4.9 +/- 1.2% after IR; p < 0.001), but not when preceded by RIPC (8.0 +/- 0.8% after IR; p = NS); RIPC did not protect after 4 h (4.9 +/- 1.1% after IR; p < 0.001), but protected at 24 (8.7 +/- 1.1% after IR; p = NS) and 48 h (8.8 +/- 1.4% after IR; p = NS). Trimetaphan attenuated early (8.3 +/- 1.1% before IR, 4.2 +/- 0.9% after IR; p < 0.05) and delayed (7.3 +/- 1.0% before IR, 2.3 +/- 0.6% after IR, p < 0.001) RIPC. Remote ischemic preconditioning in humans has two phases of protection against endothelial IR injury; an early (short) and late (prolonged) phase, both of which are neuronally mediated. The potential for late phase RIPC to provide prolonged protection during clinical IR syndromes merits investigation.