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Remote ischemic perconditioning (RIPerC) and remote ischemic postconditioning (RIPostC) have been previously demonstrated to protect the myocardium against ischemia/reperfusion (IR) injury. However, their combined effects remain to be fully elucidated. In order to investigate this, the present study used an in vivo rat model to assess whether synergistic effects are produced when RIPerC is combined with RIPostC. The rats were randomly assigned to the following groups: Sham, IR, RIPerC, RIPostC and RIPerC + RIPostC groups. The IR model was established by performing 40 min of left coronary artery occlusion, followed by 2 h of reperfusion. RIPerC and RIPostC were induced via four cycles of 5 min occlusion and 5 min reperfusion of the hindlimbs, either during or subsequent to myocardial ischemia. On measurement of infarct sizes, compared with the IR group (49.45±6.59%), the infarct sizes were significantly reduced in the RIPerC (34.36±5.87%) and RIPostC (36.04±6.16%) groups (P&lt;0.05). However, no further reduction in infarct size was observed in the RIPerC + RIPostC group (31.43±5.43%; P&gt;0.05), compared with the groups treated with either RIPerC or RIPostC alone. Activation of the reperfusion injury salvage kinase (RISK) Akt, extracellular signal‑regulated kinase 1/2 and glycogen synthase kinase‑3β, and survivor activating factor enhancement (SAFE) signal transducer and activator of transcription‑3 pathways were enhanced in the RIPerC, RIPostC and the RIPerC + RIPostC groups, compared with the IR group, with no difference among the three groups. Therefore, whereas RIPerC and RIPostC were equally effective in providing protection against myocardial IR injury, the combination of RIPerC and RIPostC failed to provide further protection than treatment with either alone. The cardioprotective effects were found to be associated with increased activation of the RISK and SAFE pathways.

molecular medicine reports

Combination of remote ischemic perconditioning and remote ischemic postconditioning fails to increase protection against myocardial ischemia/reperfusion injury, compared with either alone