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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)461-471
Number of pages11
JournalJACC: Basic to Translational Science
Volume1
Issue number6
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Fingerprint

Purinergic P1 Receptors
Adenosine
Endothelium
Ischemia
Extremities
Neural Pathways
Ischemic Preconditioning
Reperfusion Injury
Clinical Trials

Keywords

  • adenosine
  • endothelium
  • ischemia
  • pre-conditioning

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Adenosine Receptor Activation in the “Trigger” Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s). / Contractor, Hussain; Lie, Rasmus Haarup; Cunnington, Colin; Li, Jing; Støttrup, Nicolaj B.; Manlhiot, Cedric; Bøtker, Hans Erik; Schmidt, Michael R.; Forfar, J. Colin; Ashrafian, Houman; Redington, Andrew; Kharbanda, Rajesh K.

In: JACC: Basic to Translational Science, Vol. 1, No. 6, 01.10.2016, p. 461-471.

Research output: Contribution to journalArticle

Contractor, H, Lie, RH, Cunnington, C, Li, J, Støttrup, NB, Manlhiot, C, Bøtker, HE, Schmidt, MR, Forfar, JC, Ashrafian, H, Redington, A & Kharbanda, RK 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, vol. 1, no. 6, pp. 461-471. https://doi.org/10.1016/j.jacbts.2016.06.002
Contractor, Hussain ; Lie, Rasmus Haarup ; Cunnington, Colin ; Li, Jing ; Støttrup, Nicolaj B. ; Manlhiot, Cedric ; Bøtker, Hans Erik ; Schmidt, Michael R. ; Forfar, J. Colin ; Ashrafian, Houman ; Redington, Andrew ; Kharbanda, Rajesh K. / Adenosine Receptor Activation in the “Trigger” Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s). In: JACC: Basic to Translational Science. 2016 ; Vol. 1, No. 6. pp. 461-471.
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