The dynamic equilibrium between NO and superoxide is very important to regulation of vascular toneand may regulate reactions within the cardiomyocyte also. Heme oxygenase, yet another enzyme active in the response to oxidative stress, has also been proven to reduce infarct size and apoptosis. Despite the evidence that events during ischemia led to cell death, following studies raised the possibility that events during reperfusion were equally important to muscle salvage, or even more so. The observations that apoptosis occurred regarding the reperfusion, and that preconditioning stopped apoptosis, Dub inhibitors led researchers to target attention on reperfusion injury. More recently, the identification of several interventions that are protective when given after ischemia, at the on-set of reperfusion, support the concept that cell death isn’t established until time during reperfusion. While ischemic preconditioning and pharmacologic preconditioning differ in some features, they share in common the activation of protein kinase C, a dependence on the opening of the mitochondrial KATP channel, and an early burst of ROS production. Additional studies have implicated ERK, PI3K, Akt/PKB, and p70S6K. Nitric oxide is considered to be important in an increasing number of studies, and both Mitochondrion immediate and delayed preconditioning claim that exogenous NO activates guanylyl cyclase, resulting in activation of cGMP dependent kinase and subsequent effects on mitoKATP. The value of protein kinase C has been demonstrated through utilization of inhibitors including chelerythrine, little peptide agonists and antagonists, and through genetic manipulation. Most evidence points to protein kinase C, while some studies have implicated the delta isoform. Pingshowed that preconditioning induced translocation of PKC to mitochondria, while PKC translocated from cytosol to an unspecified area, possibly the Triton X 100insoluble fraction. Phosphorylation of cytoskeletal elements by PKC can change ATP utilization, and contractility, Ca2 awareness, with potentially positive effects on survival, for that reason, a beneficial role for PKC cannot be excluded. But, ATP-competitive Chk inhibitor a peptide antagonist of PKC has been shown to reduce infarct size in transgenic mice. Even though the BH3 only Bcl 2 family member, Bad, has been implicated, the downstream targets of PKC are not known. Other studies identify mitoKATP whilst the ultimate goal, even though additional protein kinases might be involved. In many studies, NO has been proven to play a beneficial purpose, and many studies have demonstrated a path involving guanylyl cyclase, PKG, and the mitoKATP. NO may possibly not be entirely harmless, however, since it can combine with superoxide to create the very reactive peroxynitrite radical, which can interact with the mitochondrial electron transfer processes to permanently inhibit respiration and ATP generation, while NO can reversibly reduce respiration.