Activation of preconditioning: Ischemic preconditioning, consisting in episodes of ischemia as short as 5 minutes, followed by reperfusion, has been showed to protect the heart from a subsequent longer coronary artery occlusion by markedly reducing the amount of necrosis. Adenosine plays a key role in triggering ischemic preconditioning. Indeed, stimulation of A1 adenosine receptors triggers a complex pathway including the epsilon isoform of protein kinase C, the ATP-dependent potassium channels, the mitochondrial permeability transition pores as well as others, like a paradoxical protective release of oxygen radicals eventually making cells more resistant to ischemia. In humans, examples of preconditioning are the preinfarction angina and the angina "warm-up phenomenon". Preconditioning can be reproduced experimentally by repetitive balloon inflations in the coronary artery that have as principal consequences less chest pain and ST-segment elevation. Pharmacological preconditioning can be induced by intravenous or intracoronary administration of adenosine or A1 agonists of adenosine. In a recent study in rabbits authors observed an anti-infarct effect of clopidogrel and cangrelor (the intravenous analog of ticagrelor) and that it was not the result from blockade of platelet aggregation, but rather from activation of the signal transduction pathway of pre- and postconditioning, involving the reperfusion injury salvage kinases (RISK) including Akt and ERK as well as adenosine A2B receptors, mitochondrial KATP channels, and redox signalingi. This cardioprotective effect of cangrelor was confirmed in a primate model.