The cardioprotective effect of sevoflurane depends on protein kinase C activation, opening of mitochondrial K+ ATP channels, and the production of reactive oxygen species

Several studies suggest that the cardioprotective effect of sevoflurane depends on protein kinase C (PKC) activation, mitochondrial K-ATP(+) channel (mitoK(ATP)(+)) opening, and reactive oxygen species (ROS). However, evidence for their involvement was obtained in separate experimental models. Here, we studied the relative roles of PKC, mitoK(ATP)(+), and ROS in sevoflurane-induced cardioprotection in one model. Rat trabeculae were subjected to simulated ischemia by applying metabolic inhibition (MI) through buffer containing NaCN, followed by 60-min reperfusion. Recovery of active force (F-a) was assessed as percentage of pre-MI force. In time controls, F-a amounted 60% +/- 5% at the end of the experiment. The recovery of F-a after MI was reduced to 28% +/- 5% (P = 0.045 versus time control), whereas sevoflurane reversed the detrimental effect of MI (F-a recovery, 67% +/- 8%; P = 0.01 versus MI). The PKC inhibitor chelerythrine, the mitoK(ATP)(+) inhibitor 5-hydroxy decanoic, and the ROS scavenger N-(2-mercaptopropionyl)-glycine all completely abolished the protective effect of sevoflurane (recovery of F-a, 31% +/- 8%, 33% +/- 8%, and 24% +/- 9% for chelerythrine, 5-hydroxy decanoic, and N-(2-mercaptopropionyl)glycine, respectively). In conclusion, PKC activation, mitoK(ATP)(+) channel opening, and ROS production are all essential for sevoflurane-induced cardioprotection. These signaling events are arranged in series within a common signaling pathway, rather than in parallel cascades. Our findings implicate that the perioperative use of sevoflurane preserves cardiac function by preventing ischemia-reperfusion injury.