Antagonistic actions of halothane and sevoflurane on spontaneous Ca 2+ release in rat ventricular myocytes

Abstract

BACKGROUND: Halothane has been reported to sensitize Ca release from the sarcoplasmic reticulum (SR), which is thought to contribute to its initial positive inotropic effect. However, little is known about whether isoflurane or sevoflurane affect the SR Ca release process, which may contribute to the inotropic profile of these anesthetics. METHODS: Mild Ca overload was induced in isolated rat ventricular myocytes by increase of extracellular Ca to 2 mm. The resultant Ca transients due to spontaneous Ca release from the SR were detected optically (fura-2). Cells were exposed to 0.6 mm anesthetic for a period of 4 min, and the frequency and amplitude of spontaneous Ca transients were measured. RESULTS: Halothane caused a temporary threefold increase in frequency and decreased the amplitude (to 54% of control) of spontaneous Ca transients. Removal of halothane inhibited spontaneous Ca release before it returned to control. In contrast, sevoflurane initially inhibited frequency of Ca release (to 10% of control), whereas its removal induced a burst of spontaneous Ca release. Isoflurane had no significant effect on either frequency or amplitude of spontaneous Ca release on application or removal. Sevoflurane was able to ameliorate the effects of halothane on the frequency and amplitude of spontaneous Ca release both on application and wash-off. CONCLUSIONS: Application of halothane and removal of sevoflurane sensitize the SR Ca release process (and vice versa on removal). Sevoflurane reversed the effects of halothane, suggesting they may act at the same subcellular target on the SR. © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.