Concentration-dependent inotropic effects of halothane, isoflurane and sevoflurane on rat ventricular myocytes

We have described the concentration-dependent : inotropic effects of haloth ane, isoflurane and sevoflurane on rat ventricular cells and investigated t he role of the sarcoplasmic reticulum (SR) in these inotropic actions. Sing le ventricular myocytes, isolated from rat hearts, were stimulated electric ally at I Hz and contractions recorded optically. Cells were exposed to a r ange of concentrations of halothane, isoflurane or sevoflurane for a period of I min to determine the concentration-dependency of their inotropic acti ons. For each anaesthetic, the peak negative inotropic action was determine d early during an exposure, and sustained negative inotropic action was mea sured at steady-state just before wash-off. In some experiments, cells were equilibrated with ryanodine I mu mol litre(-1) to investigate the role of the SR in these intropic effects. Halothane caused a concentration-dependen t initial increase in contractions (to mean 130 (SEM 28)% at 10 mmol litre( -1)) followed by rapid onset of a negative inotropic effect (K-0.5 0.34 mmo l litre(-1) for peak effect; K-0.5 0.46 mmol litre(-1) for sustained effect ). Exposure to isoflurane induced a small potentiation of contractions in s ome cells, followed by a concentration-dependent decrease in contraction in all cells (K-0.5 0.85 mmol litre(-1) for peak effect; K-0.5 1.92 mmol litr e(-1) for sustained effect); contractions recovered partially during a I-mi n exposure. On wash-off, contractions were increased transiently above cont rol. Sevoflurane caused a large initial decrease in contraction which then returned rapidly towards control (K-0.5 0.2 mmol litre(-1) for peak effect; K-0.5 2.57 mmol litre(-1) for sustained effect). In common with isoflurane , removal of sevoflurane caused a transient increase in contractions above control. After exposure to ryanodine, the positive inotropic effects of hal othane and isoflurane did not occur, and recovery of contractions during ex posure to isoflurane and sevoflurane was abolished as was the transient inc rease in contractions seen on wash-off, indicating that these effects were mediated via the SR. Halothane had the most potent sustained negative inotr opic effect but there was little difference between the negative inotropic effects of isoflurane and sevoflurane at clinically relevant concentrations . At higher concentrations, sevoflurane caused a less potent negative inotr opic effect than isoflurane. The SR plays a major role in the effects of al l three anaesthetics. One possible mechanism underlying the initial potenti ation of contraction by halothane (and isoflurane) may be sensitization of the Ca2+-induced Ca2+-release process of the SR.