The Cardioprotective Effect of Sevoflurane Depends on Protein Kinase C Activation, Opening of Mitochondrial K+ ATP Channels, and the Production of Reactive Oxygen Species

Wouter De Ruijter, René J.P. Musters, Christa Boer*, Ger J.M. Stienen, Warner S. Simonides, Jaap J. De Lange

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 (Fa) was assessed as percentage of pre-MI force. In time controls, Fa 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 Fa, 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.

Original languageEnglish
Pages (from-to)1370-1376
Number of pages7
JournalAnesthesia and Analgesia
Volume97
Issue number5
DOIs
Publication statusPublished - 1 Jan 2003

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