Effects of isoflurane, sevoflurane, and halothane on myofilament Ca2+ sensitivity and sarcoplasmic reticulum Ca2+ release in rat ventricular myocytes

Background: The aim of this study was to describe and compare the effects o f isoflurane, sevoflurane, and halothane at selected concentrations (i.e., concentrations that led to equivalent depression of the electrically evoked Ca2+ transient) on myofilament Ca2+ sensitivity, sarcoplasmic reticulum (S R) Ca2+ content, and the fraction of SR Ca2+ released during electrical sti mulation (fractional release) in rat ventricular myocytes. Methods: Single rat ventricular myocytes loaded with fura-2 were electrical ly stimulated at 1 Hz, and the Ca2+ transients and contractions were record ed optically. Cells were exposed to each anesthetic for 1 min. Changes In m yofilament Ca2+ sensitivity were assessed by comparing the changes in the C a2+ transient and contraction during exposure to anesthetic and low Ca2+. S R Ca2+ content was assessed by exposure to 20 mM caffeine. Results: Isoflurane and halothane caused a depression of myofilament Ca2+ s ensitivity, unlike sevoflurane, which had no effect on myofilament Ca2+ sen sitivity. All three anesthetics decreased the electrically stimulated Ca2transient. SR Ca2+ content was reduced by both isoflurane and halothane but was unchanged by sevoflurane, Fractional release was reduced by both isofl urane and sevoflurane, but was unchanged by halothane. Conclusions: Depressed myofilament Ca2+ sensitivity contributes to the nega tive inotropic effects of isoflurane and halothane but not sevoflurane. The decrease in the Ca2+ transient is either responsible for or contributory t o the negative Inotropic effects of all three anesthetics and is either pri marily the result of a decrease in fractional release (isoflurane and sevof lurane) or primarily the result of a decrease in SR Ca2+ content (halothane ).