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 (Ca(2+)) 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) Ca(2+) content was assessed by rapid application of caffeine. All experiments were carried out at 36-37 degrees C. RESULTS: The amplitude of shortening, the electrically evoked Ca(2+) transient, SR Ca(2+) content and myofilament Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) transient, SR Ca(2+) content and myofilament Ca(2+) sensitivity were qualitatively similar in control and STZ myocytes and were all depressed to the same extent by halothane.
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 (Ca(2+)) transients were measured (fura-2) in ventricular myocytes isolated from control and streptozotocin (STZ)-induced diabeticrats in the absence and presence of halothane 0.6 mmol litre(-1) at 1 Hz stimulation. Sarcoplasmic reticulum (SR) Ca(2+) content was assessed by rapid application of caffeine. All experiments were carried out at 36-37 degrees C. RESULTS: The amplitude of shortening, the electrically evoked Ca(2+) transient, SR Ca(2+) content and myofilament Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 diabeticrat. Contractility, the cytosolic Ca(2+) transient, SR Ca(2+) content and myofilament Ca(2+) sensitivity were qualitatively similar in control and STZ myocytes and were all depressed to the same extent by halothane.
Authors: Lina T Al Kury; Vadym Sydorenko; Manal Ma Smail; Muhammad A Qureshi; Anatoly Shmygol; Dimitrios Papandreou; Jaipaul Singh; Frank Christopher Howarth Journal: J Diabetes Investig Date: 2020-11-30 Impact factor: 4.232