Remote Ischemic Postconditioning Improves Myocardial Dysfunction Via the Risk and Safe Pathways in a Rat Model of Severe Hemorrhagic Shock

Patients who have been resuscitated after severe hemorrhagic shock still have a high mortality rate. Previously published literature has suggested that remote ischemic postconditioning (RIPostC) has a cardioprotective effect, but few studies have focused on RIPostC performed after severe hemorrhagic shock. In this study, we aim to explore the effects and mechanism of RIPostC on myocardial ischemia and reperfusion injuries after hemorrhagic shock.Fifty male rats were randomized into four groups: sham, control, remote ischemic per-conditioning (RIPerC), and RIPostC. Hemorrhagic shock was induced by removing 45% of the estimated total blood volume. Remote ischemic conditioning (RIC) was induced by four cycles of limb ischemia for 5 min followed by 5 min of reperfusion, during and after resuscitation for the RIPerC and RIPostC groups, respectively. Myocardial function, survival rate, IL-6, IL-10, and SOD were detected. Myocardial damage was histopathologically analyzed, and proteins related to the reperfusion injury salvage kinase (RISK) pathway (Akt, MEK, ERK1/2) and the survival activating factor enhancement (SAFE) pathway (STAT-3 and STAT5) were measured.Compared with the control group, the ejection fraction and myocardial performance indexes were significantly better in both RIC groups 2 h after resuscitation. Myocardial damage was attenuated and survival time increased significantly in the RIC groups. IL-6 and cardiac troponin I (cTnI) levels were notably reduced in both RIC groups. Only RIPostC had significantly increased levels of SOD and IL-10. The SAFE and RISK pathways were activated by RIPostC, whereas the effect of RIPerC was not significant.RIPostC attenuated myocardial dysfunction and survival outcomes via the activation of the SAFE and RISK pathways in this rat model of hemorrhagic shock. RIPerC improves myocardial dysfunction, but might not do so via the SAFE and RISK pathways.