Sevoflurane postconditioning prevents activation of caspase 3 and 9 through antiapoptotic signaling after myocardial ischemia–reperfusion

Purpose Volatile anesthetic postconditioning reduces apoptosis through antiapoptotic signaling. Whether sevoflurane postconditioning prevents activation of caspase 9 and 3, which are implicated in the initiation and execution step of apoptosis, is not known. Methods Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion [control (CTL)]. Anesthetic postconditioning was elicited with sevoflurane (2%) for 2 min at reperfusion onset (POST). LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt (protein kinase B) inhibitor; and PD98059, extracellular signal-regulated kinase 1/2 (ERK) inhibitor, were administered for 10 min before ischemia and throughout the reperfusion period in POST (POST + LY, POST + PD). Left-ventricular-developed (LVDP) and LV end-diastolic (LVEDP) pressures and infarct size were measured. Western blot analysis determined phosphorylated Akt and ERK expression. Myocardial caspase 3 and 9 were determined immunohistochemically. Results After ischemia–reperfusion, POST had higher LVDP (57 ± 9 vs. 38 ± 7 mmHg, p < 0.05) and lower LVEDP (21 ± 8 vs. 46 ± 15 mmHg, p < 0.05) versus CTL. Infarct size was significantly reduced in POST versus CTL (15 ± 3 vs. 41 ± 11%, p < 0.001). Phosphorylation of Akt and ERK after reperfusion was significantly increased in POST versus CTL. Immunoreactivity for caspase 3 and 9 was greater in the nucleus of myocytes and endothelial cells in CTL. POST attenuated this increased immunoreactivity. LY294002 and PD98059 abolished the effect of POST on caspase 3 and 9 immunoreactivity. Conclusions Sevoflurane postconditioning prevents activation of caspase 3 and 9, mediators of apoptosis in ischemia–reperfusion injury. This caspase activation is mediated by phosphorylation of Akt and ERK.