Remote Ischaemic Preconditioning and Sevoflurane Postconditioning Synergistically Protect Rats from Myocardial Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/NF-κB Signaling Pathway

Background/Aims: A combination sevoflurane postconditioning (SPC) and remote ischemic preconditioning (RIPC) is proved effective in an ex vivo rat heart perfusion model. However, the combined effect of those two interventions is not tested in rat myocardial ischemia/reperfusion (I/R) model, and the underlying mechanisms remain to be elucidated. This study aimed to investigate the effect in vivo using a rat myocardial I/R model and illuminate the related mechanisms. Methods: Forty male Sprague-Dawley rats were randomly divided into the following 5 groups: i) sham-operated control; ii) I/R; iii) I/R + RIPC; iv) I/R + SPC; v) I/R + RIPC + SPC. The hemodynamic parameters were recorded at the end of reperfusion. The histological changes including the infarct size were assessed using Triphenyltetrazolium chloride (TTC) staining and H&E staining. In addition, the circulating levels of cardiac enzymes (CK-MB, hs-cTnT, and cTnT) inflammatory cytokines (IL-6, IL-8, and TNF-alpha) were detected. The expression levels of apoptosis-related proteins (C-Caspase 3, PARP, Bax, and Bcl-2), proinflammatory factors (TLR4, HMGB-1, MyD88, and p65), and IKB-alpha were measured by Western blot analysis. Real-time PCR was performed to detect mRNA levels of the proinflammatory factors. Results: Both SPC and RIPC significantly reduced the infarct size, cardiac enzyme release, inflammatory cytokine secretion, and proinflammatory factor expression, and increased IKB-alpha expression JR. Zhang, J. Zhang and P. Yu contributed equally to this work. compared to I/R group. Furthermore, the combination of those two strategies had synergic infarct size limiting and anti-inflammatory effects. Conclusions: The finding of this study suggested that the combination of SPC and RIPC had a potentially cardioprotective effect through inhibiting TLR4/MyD88/NF-kappa B signaling. (C) 2017 The Author(s) Published by S. Karger AG, Basel