Lidocaine and mexiletine inhibit mitochondrial oxidation in rat ventricular myocytes

Citation
Y. Tsutsumi et al., Lidocaine and mexiletine inhibit mitochondrial oxidation in rat ventricular myocytes, ANESTHESIOL, 95(3), 2001, pp. 766-770
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Journal title
ANESTHESIOLOGY
ISSN journal
0003-3022 → ACNP
Volume
95
Issue
3
Year of publication
2001
Pages
766 - 770
Database
ISI
SICI code
0003-3022(200109)95:3<766:LAMIMO>2.0.ZU;2-G
Abstract
Background Accumulating evidence suggests that mitochondrial rather than sa rcolemmal adenosine triphosphate-sensitive K+ (K-ATP) channels may have an important role in the protection of myocardium during ischemia. Because bot h lidocaine and mexiletine are frequently used antiarrhythmic drugs during myocardial ischemia, it is important to investigate whether they affect mit ochondrial K-ATP, channel activities. Methods: Male Wistar rats were anesthetized with ether. Single, quiescent v entricular myocytes were dispersed enzymatically. The authors measured flav oprotein fluorescence to evaluate mitochondrial redox state. Lidocaine or m exiletine was applied after administration of diazoxide (25 muM), a selecti ve mitochondrial K-ATP channel opener. The redox signal was normalized to t he baseline flavoprotein fluorescence obtained during exposure to 2,4-dinit rophenol, a protonophore that uncouples respiration from ATP synthesis and collapses the mitochondrial potential. Results: Diazoxide-induced oxidation of flavoproteins and the redox changes were inhibited by 5-hydroxydecanoic acid, a selective mitochondrial KATP c hannel blocker, suggesting that flavoprotein fluorescence can be used as an index of mitochondrial oxidation mediated by mitochondrial K-ATP channels. Lidocaine (10(-3) to 10 mM) and mexiletine (10(-3) to 10 mM) reduced oxida tion of the mitochondrial matrix in a dose-dependent manner with an EC50 of 98 +/- 63 mum for lidocaine and 107 +/- 89 mum for mexiletine. Conclusions: Both lidocaine and mexiletine reduced flavoprotein fluorescenc e induced by diazoxide in rat ventricular myocytes, indicating that these a ntiarrhythmic drugs may produce Impairment of mitochondrial oxidation media ted by mitochondrial K-ATP channels.