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

Loukogeorgakis, SP; Panagiotidou, AT; Broadhead, MW; Donald, A; Deanfield, JE; MacAllister, RJ; (2005) Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans - Role of the autonomic nervous system. J AM COLL CARDIOL , 46 (3) 450 - 456. 10.1016/j.jacc.2005.04.044.

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Abstract

OBJECTIVES The aim of this study was to characterize the time course and neuronal mechanism of remote ischemic preconditioning (RIPC) of the vasculature in humans.BACKGROUND 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.METHODS 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.RESULTS 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) RlPC.CONCLUSIONS 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 RlPC to provide prolonged protection during clinical IR syndromes merits investigation.

Type: Article
Title: Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans - Role of the autonomic nervous system
DOI: 10.1016/j.jacc.2005.04.044
Keywords: REDUCES INFARCT SIZE, DELAYED CARDIOPROTECTION, IN-VIVO, MYOCARDIAL-INFARCTION, ADENOSINE RECEPTORS, CORONARY-OCCLUSION, HEART, BRADYKININ, TOLERANCE, CHANNELS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
URI: http://discovery.ucl.ac.uk/id/eprint/146909
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