Rithalia A, Qureshi M A, Howarth F C, Harrison S M
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Br J Anaesth. 2004 Feb;92(2):246-53. doi: 10.1093/bja/aeh048.
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.
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.
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.
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.
挥发性麻醉剂（如氟烷）所影响的一些细胞靶点，这些靶点会导致这些药物的负性肌力作用，在糖尿病性心肌病进展过程中也会受到影响。先前的一份报告表明，氟烷对糖尿病动物乳头肌收缩的抑制作用较小，因此本研究的目的是探讨这种作用潜在的机制。
在1Hz刺激下，分别在不存在和存在0.6mmol/L氟烷的情况下，测量从对照大鼠和链脲佐菌素（STZ）诱导的糖尿病大鼠分离的心室肌细胞的收缩力和胞质钙离子（Ca(²⁺)）瞬变（用fura-2）。通过快速施加咖啡因评估肌浆网（SR）Ca(²⁺)含量。所有实验均在36 - 37℃下进行。
缩短幅度、电诱发的Ca(²⁺)瞬变、SR Ca(²⁺)含量和肌丝Ca(²⁺)敏感性，虽不受STZ处理影响，但在对照和STZ处理的肌细胞中，氟烷均使其显著降低至相似程度。与对照相比，STZ处理大鼠的肌细胞收缩和Ca(²⁺)瞬变的时间进程延长，但氟烷并未使其进一步改变。STZ处理似乎减少了细胞内Ca(²⁺)外流，氟烷可逆转这一效应。
与先前的报告相反，我们未发现氟烷对STZ诱导的糖尿病大鼠肌细胞负性肌力作用有改善的证据。对照和STZ处理的肌细胞在收缩力、胞质Ca(²⁺)瞬变、SR Ca(²⁺)含量和肌丝Ca(²⁺)敏感性方面在性质上相似，且均被氟烷抑制至相同程度。
