Combined Vagal Stimulation and Limb Remote Ischemic Perconditioning Enhances Cardioprotection via an Anti-inflammatory Pathway

Various combined interventions to acquire enhanced cardioprotection are prevalent focuses of current research. This randomized experiment assessed whether combined vagal stimulation perconditioning (VSPerC) and limb remote ischemic perconditioning (LRIPerC) improved cardioprotection compared to the use of either treatment alone in an in vivo rat model of myocardial ischemia/reperfusion injury. A total of 100 male Sprague Dawley rats were randomly allocated into five groups: sham group, ischemia/reperfusion (IR) group, VSPerC group, LRIPerC group, and combined VSPerC and LRIPerC (COMPerC) group. Serum enzymatic markers, inflammatory cytokines, myocardial inflammatory cytokines, and infarct size were assessed. Infarct size decreased significantly in the COMPerC group compared to the VSPerC and LRIPerC groups. Serum intercellular adhesion molecule 1 (ICAM-1) level at 120 min of reperfusion, myocardial interleukin-1 (IL-1), ICAM-1, and tumor necrosis factor α (TNF-α) levels in the ischemic region decreased significantly in the COMPerC group compared to the VSPerC group, but myocardial IL-10 levels in the nonischemic region increased markedly in the COMPerC group. Serum TNF-α levels at 30, 60, and 120 min of reperfusion; serum IL-1, IL-6, ICAM-1, and high mobility group box-1 protein (HMGB-1) levels at 120 min of reperfusion; and myocardial IL-1, IL-6, ICAM-1, and TNF-α levels in the ischemic region decreased significantly in the COMPerC group compared to the LRIPerC group. However, myocardial IL-10 levels in both ischemic and nonischemic regions were evidently higher in the COMPerC group. This study concludes that combined VSPerC and LRIPerC enhances cardioprotection compared to either treatment alone. This result is likely attributable to a more potent regulation of inflammation.