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

Highlights •Pre-conditioning has emerged as a potentially powerful means of reducing ischemia-reperfusion injury. •Several animal models have implicated adenosine in pre-conditioning pathways, but its role in human physiology is unknown. •In human volunteers, the authors demonstrate that adenosine receptor activation in “trigger” tissue is an important step in initiating a pre-conditioning signal, but adenosine receptor blockade in “target” tissue does not block the protection afforded by pre-conditioning. •The authors also demonstrate that pre-conditioning elaborates a transferrable cardioprotective factor(s) into the serum. This elaboration is prevented by adenosine receptor blockade but can be mirrored by the infusion of exogenous adenosine. •An improved understanding of the physiological effectors of pre-conditioning may allow for better targeted clinical studies of pre-conditioning and pre-conditioning mimetics in the future.