Defective cardiac function is a frequent complication of human diabetes and is also a feature of experimentally induced diabetes (Yu et al. 1994; Tamada et al. 1998). In the normal heart volatile anaesthetics such as halothane have been shown to exert a potent negative inotropic effect (Housmans & Murat, 1988). In this study we have investigated the effects of halothane on the mechanism of contraction in ventricular myocytes from streptozotocin (STZ)-induced diabetic rats compared with age-matched controls. STZ (60 mg kg-1) was administered intraperitoneally (I.P.) to male Wistar rats (250Ð300 g). Animals were killed humanely and ventricular myocytes were isolated by a combination of enzymatic and mechanical dispersal techniques and contraction was measured via a video edge detection system (Howarth & Levi, 1998). Cells were superfused with a normal Tyrode (NT) solution containing 1 mM Ca2+. Following a train of steady-state contractions, myocytes were rapidly superfused with halothane (0.6 mM) for 1 min.
At 8Ð12 weeks after STZ treatment blood glucose levels in diabetic (mean ± S.E.M., 378.3 ± 17.6 mg dl-1, n = 9) animals were significantly higher (P < 0.01; independent samples t test) compared with controls (88.3 ± 3.1 mg dl-1, n = 9). Other characteristics of diabetic animals included significantly (P < 0.05; independent samples t test) reduced body weight and heart weight. The time to peak of contraction (tpk) of myocyte shortening was significantly (P < 0.01; independent samples t test) prolonged in STZ myocytes (137.2 ± 4.1 ms, n = 32) versus control (105.5 ± 2.0 ms, n = 31), and was significantly (P < 0.01; paired t test) reduced when comparing pre- and post-application of halothane in both control (94.6 ± 2.4 ms, n = 31) and STZ myocytes (119.3 ± 3.4 ms, n = 32). Halothane significantly (P < 0.01; independent samples t test) reduced amplitude of contraction in both control (from 100 to 65.9 ± 2.7 %, n = 31) and STZ-induced (from 100 to 40.9 ± 3.2 %, n = 32) myocytes. This response was significantly (P < 0.01; independent samples t test) greater in STZ-induced myocytes compared with control. The time from the peak of contraction to half-decay was not significantly different between control and STZ cells in the presence or absence of halothane, but was significantly (P < 0.01; paired t test) decreased in control (46.5 ± 2.1 ms, n = 31 vs. 42.5 ± 2.0 ms, n = 31) and STZ-induced (48.6 ± 1.8 ms, n = 32 vs. 45.1 ± 1.9 ms, n = 32) myocytes comparing pre- and post-application of halothane, respectively. These results demonstrate that halothane evokes a markedly pronounced negative inotropic effect in the STZ-induced diabetic heart compared with the normal heart.
This work was supported by the British Heart Foundation.
All procedures accord with current UK legislation.