The negative inotropic effects of halothane on contractile properties in the streptozotocin-induced diabetic rat heart

University of Central Lancashire / University of Liverpool (2002) J Physiol 543P, S172

Communications: The negative inotropic effects of halothane on contractile properties in the streptozotocin-induced diabetic rat heart

N.K. Bracken*, M.A. Qureshi†, W. Winlow*, J. Singh*, S.M. Harrison‡ and F.C. Howarth†

*Department of Biological Sciences, University of Central Lancashire, Preston, ‡School of Biomedical Sciences, University of Leeds, Leeds and †Department of Physiology, FMHS, United Arab Emirates University, Al Ain, United Arab Emirates

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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.



Where applicable, experiments conform with Society ethical requirements.

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