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British Journal of Anaesthesia, 2004, Vol. 92, No. 2 246-253
© 2004 The Board of Management and Trustees of the British Journal of Anaesthesia

Laboratory Investigations

Effects of halothane on contraction and intracellular calcium in ventricular myocytes from streptozotocin-induced diabetic rats

A. Rithalia1, M. A. Qureshi2, F. C. Howarth2 and S. M. Harrison*,1

1 School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK. 2 Department of Physiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates

*Corresponding author. E-mail: S.M.Harrison@Leeds.ac.uk

Background. Some of the cellular targets affected by volatile anaesthetics (e.g. halothane) which contribute to the negative inotropic effects of these agents are also affected during the progression of diabetic cardiomyopathy. A previous report suggested that halothane inhibited contraction to a lesser extent in papillary muscle from diabetic animals and so the aim of this study was to investigate possible mechanisms underlying this effect.

Methods. Contractility and cytosolic calcium ion (Ca2+) transients were measured (fura-2) in ventricular myocytes isolated from control and streptozotocin (STZ)-induced diabetic rats in the absence and presence of halothane 0.6 mmol litre–1 at 1 Hz stimulation. Sarcoplasmic reticulum (SR) Ca2+ content was assessed by rapid application of caffeine. All experiments were carried out at 36–37°C.

Results. The amplitude of shortening, the electrically evoked Ca2+ transient, SR Ca2+ content and myofilament Ca2+ sensitivity, though not altered by STZ treatment, were significantly reduced by halothane to a similar extent in control and STZ myocytes. The time course of contraction and Ca2+ transient were prolonged in myocytes from STZ-treated rats compared with controls but this was not altered further by halothane. STZ treatment appeared to reduce Ca2+ efflux from the cell, an effect reversed by halothane.

Conclusions. In contrast to a previous report, we could find no evidence of amelioration of the negative inotropic effect of halothane in myocytes from the STZ-induced diabetic rat. Contractility, the cytosolic Ca2+ transient, SR Ca2+ content and myofilament Ca2+ sensitivity were qualitatively similar in control and STZ myocytes and were all depressed to the same extent by halothane.

Br J Anaesth 2004; 92: 246–53


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