Remote ischemic preconditioning does not induce activation of Akt and STAT5 in the rat heart.

Remote ischemic preconditioning (RIPC) is hypothesized to be a promising cardioprotective strategy to protect hearts against ischemia and reperfusion (I/R) injury; however, the current understanding of the underlying signal transduction pathways involved remains unclear. It has been previously demonstrated that protein kinase B/AKT, which is a crucial protein of the reperfusion injury salvage kinases pathway, and STAT5, which is a member of the survivor activating factor enhancement pathway, serve a pivotal role in cardioprotection. However, whether and at what time-points (TPs) RIPC leads to the activation of AKT and STAT5 in a rat model of RIPC and I/R injury remains to be determined. The present study hypothesized that RIPC may induce the phosphorylation of AKT and/or STAT5 immediately following RIPC and/or at a later TP with or without subsequent I/R. In the first set of experiments (part A), male Wistar rats were randomized into 2 groups (n=6 per group): The first group underwent RIPC via a hind limb tourniquet (4x5 min I/R episodes), while the second group received the respective sham treatment. In the second set of experiments (part B), the rats were randomized into 4 groups (n=6 per group) that either underwent RIPC or sham treatment prior to 35 min of ischemia by occlusion of the left anterior descending coronary artery followed by 120 min reperfusion or a respective sham treatment. At the end of the experiments, the heart tissue was isolated in order to analyze the phosphorylation levels of AKT and STAT5. The results revealed that RIPC did not induce the immediate or late phosphorylation of AKT or STAT5. In addition, following I/R, the activation of AKT and STAT5 was not modulated by RIPC. In conclusion, the findings of the present study suggested that RIPC-induced cardioprotection may not be mediated by the activation of AKT or STAT5 at the investigated TPs.