Activation Of Protective Intracellular Signaling Pathways In The Heart By Skeletal Muscle-Derived Cytokines During Remote Ischemic Preconditioning

Background: Although remote ischemic preconditioning (RIPC) has cardioprotective effects in ischemia/reperfusion injury, the mechanism of cardioprotection during RIPC is not fully understood. Hematopoietic or gp130 cytokines have been shown to have cardioprotective effects in ischemia/reperfusion injury. We hypothesized that skeletal muscle derived-cytokines induced by RIPC would activate cardiac intracellular signaling that has cardioprotective effects on ischemia/reperfusion injury. Methods and Results: We measured plasma levels of cytokines before and after RIPC in healthy volunteers (n=10). RIPC was induced by three 5-minute episodes of right upper limb ischemia with an automated blood pressure cuff inflated to 200 mmHg and by 5 minutes of cuff deflation for reperfusion. We found that interleukin-6 (IL-6) and G-CSF were significantly increased 24 hours after RIPC (IL-6: from 0.23 ± 0.05 to 0.62 ± 0.06 pg/ml, p Conclusion: These results suggest that expression of skeletal muscle-derived cytokines induced by RIPC may be a mechanism of cardioprotection during ischemia/reperfusion injury.