Sevoflurane Increases p38 Mitogen Activated Protein Kinase Phosphorylation During Ischemia, but its Cardioprotective Effect is not Blocked by SB 203580

Abstract

It remains unclear whether p38 mitogen activated protein kinase (p38 MAPK) is involved in anesthetic preconditioning (APC). We investigated the effect of inhibiting p38 MAPK activation on sevoflurane-induced APC. Isolated perfused guinea pig hearts underwent 30 min ischemia and 120 min reperfusion. APC was elicited with 2% sevoflurane administration. Inhibition of p38 MAPK was achieved using SB203580. Contractile recovery was monitored by left ventricular developed (LVDP) and end-diastolic (LVEDP) pressure. Infarct size was determined by triphenyltetrazolium chloride stain. Expression of p38 MAPK was determined by Western blot. After ischemia/reperfusion, APC hearts had higher LVDP and lower LVEDP compared to CTL. Infarct size was significantly reduced in APC. SB203580 administration failed to abolish APC. Western blot analysis demonstrated that phosphorylation of p38 MAPK was increased by APC, which was enhanced by SB 203580.In conclusion, sevoflurane increases p38 MAPK phosphorylation but this is not required for APC.