Cardioprotection by remote ischemic preconditioning exhibits a signaling pattern different from local ischemic preconditioning

Remote ischemic preconditioning (RIPC) and local ischemic preconditioning (IPC) protect the myocardium from subsequent ischemia/reperfusion (I/R) injury. In this study, the protective effects of early RIPC, IPC, and the combination of both (RIPC-IPC) were characterized. Furthermore, the hypothesis was tested that protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs), important mediators of IPC, are activated in RIPC. Infarct size, serum troponin T, and creatine kinase levels were assessed after 4 × 5-min noninvasive RIPC, local IPC, or a combination of both and 35 min of regional ischemia and 120 min of reperfusion. Protein kinase C e and the MAPKs extracellular signal-regulated MAPK (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK were analyzed by Western blot analysis and activity assays in the myocardium and skeletal muscle immediately after the preconditioning protocol. Remote ischemic preconditioning, IPC, and RIPC-IPC significantly reduced myocardial infarct size (RIPC-I/R: 54% ± 15%; IPC-I/R: 33% ± 15%; RIPC-IPC-I/R: 33% ± 15%; P < 0.05 vs. I/R [76% ± 14%]) and troponin T release (RIPC-I/R: 15.4 ± 6.4 ng/mL; IPC-I/R: 10.9 ± 7.0 ng/mL; RIPC-IPC-I/R: 9.8 ± 5.6 ng/mL; P < 0.05 vs. I/R [27.1 ± 12.0 ng/mL]) after myocardial I/R. Ischemic preconditioning led to an activation of PKCe and ERK 1/2, whereas RIPC did not lead to a translocation of PKCe to the mitochondria or phosphorylation of the MAPKs ERK 1/2, JNK 1/2, and p38 MAPK. Remote ischemic preconditioning did not induce translocation of PKCe to the mitochondria or phosphorylation of MAPKs in the preconditioned muscle tissue. Remote ischemic preconditioning, IPC, and RIPC-IPC exert early protection against myocardial I/R injury. Remote ischemic preconditioning and local IPC exhibit different activation dynamics of signal transducers in the myocardium. The studied PKC-MAPK pathway is likely not involved in the protective effects of RIPC