Murry et al. reduced infarct size in dogs through repetitive brief occlusions, preceding prolonged ischemia, and coined this phenomenon “ischemic preconditioning.”¹³ ATP breakdown was attenuated during the prolonged period of ischemia, possibly due to a decrease in contractile function prior to this ischemic period. However, others observed no beneficial effects on ATP levels in the myocardium. Downey’s group indicated the possible role of the ATP catabolite adenosine.¹⁹ Subsequently, it was shown that A ₁- and/or A₃-receptor activation or blockade by various agonists or antagonists, respectively, could augment or diminish the protective effect. Preconditioning through these receptors may involve a cascade of reations, including activation of cardiac protein-kinase C.