The concentration of acetoacetic acid, β-hydroxybutyric acid and acetone in blood may rise to very high levels in diabetic patients and cause metabolic acidosis. The aim of this study was to investigate the acute effects of acidosis on ventricular myocyte contraction and intracellular Ca2+ concentration [Ca2+]i in streptozotocin (STZ)-induced diabetic rats.
Diabetes was induced in rats by I.P. injection of STZ (60 mg kg-1). Experiments were performed in electrically stimulated (1 Hz) myocytes, maintained at 35-36 °C, from control and diabetic rats at 8-12 weeks after STZ treatment. Characteristics of shortening were measured with a video edge detector (VED-114, Crystal Biotech, USA). Intracellular [Ca2+] was measured in myocytes loaded with fura-2/AM. Electrically stimulated myocytes were exposed to normal Tyrode solution pH adjusted to either 7.4 (NT) or 6.4 (acid NT). Data are expressed as means ± S.E.M. of n observations. Statistical comparisons were performed using either an independent samples t test or one-way ANOVA followed by Bonferoni corrected t tests for multiple comparisons as appropriate. P values less than 0.05 were considered significant.
The general characteristics of STZ-induced diabetes included significant (P < 0.05) reductions in body and heart weight and a 5-fold increase in blood glucose. Time to peak shortening was significantly prolonged in myocytes from STZ-treated (131 ± 5 ms, n = 14) compared to control (109 ± 5 ms, n = 20) rats. Change of external pH from 7.4 to pH 6.4 significantly reduced the amplitude of shortening in electrically stimulated control and diabetic myocytes, but the magnitude of the negative inotropic effects of acid NT were not additionally altered by STZ-treatment. Time to peak shortening and to half relaxation in control and diabetic myocytes were not altered by exposure to acid NT. The amplitude of the Ca2+ transient was significantly reduced by acid NT but the magnitude of the response was not additionally altered by STZ-treatment. The acute effects of exposure to acid NT on myocyte shortening and Ca2+ transient were not significantly altered by STZ-induced diabetes.
Animals were killed humanely and all experimental procedures were carried out in accordance with internationally acceptable practices and were approved by Faculty of Medicine & Health Sciences, United Arab Emirates University Ethics Committee.
This work was supported by a project grant from the Faculty of Medicine and Health Sciences, United Arab Emirates University.