The cardiac “warm up” phenomenon, described more than 50 years ago in patients with coronary artery disease, refers to improvement in cardiac symptoms and physical performance following exposure to short periods of ischemia. 1 Several mechanisms, such as adaptive reduction in oxygen consumption by the ischemic myocardial region, improved oxygen supply via collateral recruitment or dilation of the stenotic vessel, and activation of an intrinsic phenomenon called ischemic preconditioning (IPC) have been proposed to account for this phenomenon. IPC refers to a process in which brief periods of ischemia improves the ability of the heart to tolerate subsequent prolonged ischemic periods. 3 It was first identified in the heart in 1986 by Murry et al, 2 and has since been demonstrated in various experimental and animal models. 3

Several triggers have been proposed for IPC, including adenosine, bradykinin, protaglandins, opiod receptors, nitric oxide, and Ca2+. 4 These triggers lead to the activation of several intracellular pathways that ultimately protect myocardial cells against injury. Although the details of these pathways have not been totally characterized, mitochondria have been shown to be key mediators of IPC. Specifically, the opening of a mitochondrial channel, called the mitochondrial ATP-sensitive potassium channel or mitoKATP is believed to be critical for the induction of IPC; drugs that activate this channel protect against ischemia and inhibitors of mitoKATP reverse these protective effects. 5 The signaling pathways that lead to the activation of mitoKATP are still under investigation. 5 In a recent article, Oldenburg et al demonstrated that in isolated rabbit adult cardiomyocytes, bradykinin increased the levels of reactive oxygen species (ROS) and this effect was reversed by inhibitors of both mitoKATP and protein kinase G (PKG). 6 Subsequent studies demonstrated that mitoKATP can be activated by the addition of exogenous cGMP and PKG, and that this effect is reversed by inhibitors of protein kinase C (PKC). 7 These results suggest that PKG transmits the cardioprotective signal to mitoKATP through a PKC-dependent pathway. It is unclear how this signal is transmitted and which isoforms of PKC are involved in this process.