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Contractor H, Lie RH, Cunnington C, et al. Adenosine Receptor Activation in the "Trigger" Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s). JACC Basic Transl Sci. 2016;1(6):461-471doi: 10.1016/j.jacbts.2016.06.002.
Contractor, H., Lie, R. H., Cunnington, C., Li, J., Støttrup, N. B., Manlhiot, C., Bøtker, H. E., Schmidt, M. R., Forfar, J. C., Ashrafian, H., Redington, A., & Kharbanda, R. K. (2016). Adenosine Receptor Activation in the "Trigger" Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s). JACC. Basic to translational science, 1(6), 461-471. https://doi.org/10.1016/j.jacbts.2016.06.002
Contractor, Hussain, et al. "Adenosine Receptor Activation in the "Trigger" Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s)." JACC. Basic to translational science vol. 1,6 (2016): 461-471. doi: https://doi.org/10.1016/j.jacbts.2016.06.002
Contractor H, Lie RH, Cunnington C, Li J, Støttrup NB, Manlhiot C, Bøtker HE, Schmidt MR, Forfar JC, Ashrafian H, Redington A, Kharbanda RK. Adenosine Receptor Activation in the "Trigger" Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s). JACC Basic Transl Sci. 2016 Sep 28;1(6):461-471. doi: 10.1016/j.jacbts.2016.06.002. eCollection 2016 Oct. PMID: 30167533; PMCID: PMC6113421.
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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).

JACC. Basic to translational science

Hussain Contractor, Rasmus Haarup Lie, Colin Cunnington, Jing Li, Nicolaj B Støttrup, Cedric Manlhiot, Hans Erik Bøtker, Michael R Schmidt, J Colin Forfar, Houman Ashrafian, Andrew Redington, Rajesh K Kharbanda

Affiliations

  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.

PMID: 30167533 PMCID: PMC6113421 DOI: 10.1016/j.jacbts.2016.06.002

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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