Transient and sustained changes in myofilament sensitivity to Ca2+ contribute to the inotropic effects of sevoflurane in rat ventricle

Background. The volatile anaesthetics isoflurane and sevoflurane induce both negative and positive inotropic effects in ventricular myocytes, the mechanisms of which are not fully understood. Previous data suggest that changes in myofilament Ca2+ sensitivity contribute to their sustained negative inotropic effects. In this study, the role of changes in myofilament Ca2+ sensitivity in both positive and negative inotropic effects of these agents was examined in intact ventricular myocytes. Methods. Contractility and cytosolic Ca2+ (fura-2) were recorded optically in ventricular myocytes stimulated electrically (1 Hz) at 30degreesC. Myofilament Ca2+ sensitivity was assessed from plots of cell length against fura-2 fluorescence ratio (Fr) from individual twitches at various points before, during and after a 1 or 4 min exposure to 0.6 mM anaesthetic. Results. Isoflurane reduced mean (sd) myofilament Ca2+ sensitivity from 10.3 (1.9) to 5.9 (1.6) mum Fr-1 (P<0.001) throughout a 1 min exposure, which returned to control on removal. In contrast, on initial exposure to sevoflurane, Ca2+ sensitivity was reduced from 10.8 (1.3) to 4.3 (0.9) mum Fr-1 (P<0.001) but this recovered partially towards control over 3 min. On removal, sensitivity was increased above control (to 17.7 (2.2) mum Fr-1; P<0.001) before preanaesthetic levels were restored. Conclusions. These data show that both isoflurane and sevoflurane reduce apparent myofilament Ca2+ sensitivity at steady state. However, sevoflurane (but not isoflurane) induced transient changes in apparent myofilament Ca2+ sensitivity, which would contribute to its inotropic profile.