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JACC Basic Transl Sci. 2016 Sep 28;1(6):461-471. doi: 10.1016/j.jacbts.2016.06.002. eCollection 2016 Oct.

Adenosine Receptor Activation in the "Trigger" Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s).

Author information

1
Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom.
2
Department of Cardiology, Skejby Hospital, Aarhus University Hospital Skejby, Aarhus, Denmark.
3
Division of Cardiology, Department of Medicine, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
4
Department of Pediatric Cardiology, the Heart Institute at Cincinnati Children's Hospital, Cincinnati, Ohio.

Abstract

Remote ischemic pre-conditioning (rIPC) has emerged as a potential mechanism to reduce ischemia-reperfusion injury. Clinical data, however, have been mixed, and its physiological basis remains unclear, although it appears to involve release of circulating factor(s) and/or neural pathways. Here, the authors demonstrate that adenosine receptor activation is an important step in initiating human pre-conditioning; that pre-conditioning liberates circulating cardioprotective factor(s); and that exogenous adenosine infusion is able to recapitulate release of this factor. However, blockade of adenosine receptors in ischemic tissue does not block the protection afforded by pre-conditioning. These data have important implications for defining the physiology of human pre-conditioning and its translation to future clinical trials.

KEYWORDS:

ANOVA, analysis of variance; Ach, acetylcholine; FMD, flow-mediated dilation; GTN, glyceryltrinitrate; IR, ischemia-reperfusion; LV, left ventricular; NMD, nitrate-mediated dilation; adenosine; endothelium; ischemia; pre-conditioning; rIPC, remote ischemic pre-conditioning

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