Remote ischemic conditioning by efuent collected from a novel isolated hindlimb model reduces infarct size in an isolated heart model

Background and Objectives: Experimental protocols for remote ischemic conditioning (RIC) utilize models in which a tourniquet is placed around the hindlimb or efuent is collected from an isolated heart. In analyzing the humoral factors that act as signal transducers in these models, sampled blood can be influenced by systemic responses, while the efuent from an isolated heart might differ from that of the hindlimb. Thus, we designed a new isolated hindlimb model for RIC and tested whether the efuent from this model could affect ischemia/reperfusion (IR) injury and if the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways are involved in RIC. Materials and Methods: Afer positioning needles into the right iliac artery and vein of rats, Krebs-Henseleit buffer was perfused using a Langendorff apparatus, and efuent was collected. The RIC protocol consisted of 3 cycles of IR for 5 minutes. In the RIC efuent group, collected efuent was perfused in an isolated heart for 10 minutes before initiating IR injury. Results: Compared with the control group, the infarct area in the RIC efuent group was signifcantly smaller (31.2%±3.8% vs. 20.6%±1.8%, p<0.050), while phosphorylation of signal transducer and activation of transcription-3 (STAT-3) was signifcantly increased. However, there was a trend of increased phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in this group. Conclusion: This is the frst study to investigate the effect of efuent from a new isolated hindlimb model afer RIC on IR injury in an isolated heart model. The RIC efuent was effective in reducing the IR injury, and the cardioprotective effect was associated with activation of the SAFE pathway.