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

Abstract

We have described the concentration-dependent inotropic effects of halothane, isoflurane and sevoflurane on rat ventricular cells and investigated the role of the sarcoplasmic reticulum (SR) in these inotropic actions. Single ventricular myocytes, isolated from rat hearts, were stimulated electrically at 1 Hz and contractions recorded optically. Cells were exposed to a range of concentrations of halothane, isoflurane or sevoflurane for a period of 1 min to determine the concentration-dependency of their inotropic actions. For each anaesthetic, the peak negative inotropic action was determined early during an exposure, and sustained negative inotropic action was measured at steady-state just before wash-off. In some experiments, cells were equilibrated with ryanodine 1 mumol litre-1 to investigate the role of the SR in these intropic effects. Halothane caused a concentration-dependent initial increase in contractions (to mean 130 (SEM 28)% at 10 mmol litre-1) followed by rapid onset of a negative inotropic effect (K0.5 0.34 mmol litre-1 for peak effect; K0.5 0.46 mmol litre-1 for sustained effect). Exposure to isoflurane induced a small potentiation of contractions in some cells, followed by a concentration-dependent decrease in contraction in all cells (K0.5 0.85 mmol litre-1 for peak effect; K0.5 1.92 mmol litre-1 for sustained effect); contractions recovered partially during a 1-min exposure. On wash-off, contractions were increased transiently above control. Sevoflurane caused a large initial decrease in contraction which then returned rapidly towards control (K0.5 0.2 mmol litre-1 for peak effect; K0.5 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 halothane and isoflurane did not occur, and recovery of contractions during exposure to isoflurane and sevoflurane was abolished as was the transient increase in contractions seen on wash-off, indicating that these effects were mediated via the SR. Halothane had the most potent sustained negative inotropic 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 inotropic effect than isoflurane. The SR plays a major role in the effects of all three anaesthetics. One possible mechanism underlying the initial potentiation of contraction by halothane (and isoflurane) may be sensitization of the Ca(2+)-induced Ca(2+)-release process of the SR.

Accuracy of cardiovascular magnetic resonance in myocarditis: comparison of MR and histological findings in an animal model

“…Consequently, this increases the sensitivity of image analysis [14]. All CMR examinations were performed under isoflurane anesthesia (2.2% isoflurane in air) due to its negative inotropic effect[15]. …”

Effects of anesthesia on conventional and speckle tracking echocardiographic parameters in a mouse model of pressure overload

“…Following a reduction in HR, the preload and ejection period increased, which led to an increase in SV and strain. However, under DA conditions, the increased administration of ISF reversed this trend by significantly reducing cardiac contraction (22,23). Due to the abnormal contraction observed in mice under DA conditions, the SV was considerably suppressed, which resulted in a reduction in strain.…”

ATP-dependent effects of halothane on SR Ca regulation in permeabilized atrial myocytes

“…In intact rat myocytes, low levels of halothane (0.1-0.5 mM) induce a transient increase in the amplitude of the electrically stimulated Ca 2+ transient [11]. This is believed to reflect dsensitisationT of the CICR mechanism.…”

“…There is also evidence that the cardioprotective effect of halogenated anaesthetics may reflect a direct action on the SR. Halothane in particular has been shown to abolish spontaneous Ca 2+ oscillations and to reduce hypercontracture following reoxygenation: effects mimicked by structurally unrelated inhibitors of SR function [5]. However, although halogenated anaesthetics have been shown to modify SR Ca 2+ release triggered by sarcolemmal Ca 2+ influx [11], their influence on Ca 2+ sparks or spontaneous Ca 2+ release has not been characterised in detail. This is of interest because recent work has shown that cytosolic changes associated with ischaemia inhibit Ca 2+ sparks and spontaneous Ca 2+ release [12][13][14].…”