Sevoflurane preconditioning protects cardiac function against ischemia/reperfusion injury through up-regulation of ROS-induced autophagy

AIM To investigate the effect and underlying mechanism of sevoflurane (SEVO) on cardiac functions after ischemia/reperfusion. METHODSIsolated rat heart perfusion model was achieved by nonrecirculating isovolumic perfusion apparatus. Twenty four male Sprague Dawley rats were divided randomly into I/R group (30 min ischemia followed by 120 min reperfusion), I/R+SEVO group (anesthetic preconditioning was performed with 2% sevoflurane for 10 min before ischemia), I/R+SEVO+NAC group and I/R+SEVO+TEMPO group (ROS-scavengers, NAC or TEMPO was administered at 30 min before ischemia). Reactive oxygen species (ROS) were determined before ischemia and after reperfusion. Western blot was performed to determine autophagy-relative proteins (including AMPK, P-AMPK, LC3-II/LC3-I and Beclin1) after reperfusion. Hemodynamic parameters including LVDP, LVDEP, ±LV dP/dtmax were determined. RESULTSSEVO preconditioning increased myocardial ROS at baseline but decreased myocardial ROS after reperfusion, which ultimately improved myocardial function. In addition, SEVO promoted AMPK activation, Beclin1 expression, and increased LC3-II/I ratio, which was inhibited by ROS-scavengers, NAC and TEMPO. CONCLUSIONSevoflurane preconditioning improves myocardial function under ischemia/reperfusion and the underlying mechanism is associated with up-regulation of ROS-induced autophagy.