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- Title
Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac remodeling in rat.
- Authors
Kim, Bo; Cho, Kyoung; Kim, Seong; Kim, Nari; Han, Jin; Kim, Jee; Kim, In
- Abstract
Ivabradine slows the heart rate (HR) by selectively inhibiting the I(f) current in the sinus node without a negative inotropic effect. We aimed to investigate the effects of ivabradine on thyroid hormone-induced left ventricular (LV) remodeling and ion channel activity in rats. Thirty Sprague-Dawley rats were randomly selected into the groups of control, injection of l-thyroxine (T, 100 μg/kg/day), and injection of l-thyroxine with ivabradine (T-Iva, T + 10 mg/kg/day). Circumferential ( S), radial ( S), and longitudinal ( S) strains were assessed by speckle tracking echocardiography (STE). Myocardial width and fibrosis were assessed from histological LV cross sections, and electrophysiological analysis was done by patch clamp method. In comparison with the control group, the T group showed significantly increased HR and LV end-systolic diameter (LVESD), reduced S (−16.04 ± 3.95 vs. −7.84 ± 2.98 %, p < 0.001), S (20.94 ± 3.81 vs. 40.57 ± 6.70 %, p < 0.001), and S (−15.26 ± 5.15 vs. −23.83 ± 5.19 %, p < 0.001), despite the 59.5 % increase of average I density at 0 mV (13.4 ± 1.2 pA/pF) compared to control group (8.4 ± 0.8 pA/pF). Treatment with ivabradine significantly reduced HR and LVESD, improved SR, S and SR in the T group, and the average I density at 0 mV in T-Iva groups (9.9 ± 1.6 pA/pF) was restored to the control level. Morphologically, the T group showed significantly increased cardiomyocyte width (25.3 ± 1.89 vs. 18.90 ± 1.14 μm in control, p < 0.001) and fibrosis, which were not significantly changed by ivabradine. In conclusion, selective HR reduction by ivabradine attenuates thyroid hormone-induced reduction of myocardial deformation and altered intracellular Ca handling without modification of the myocyte hypertrophy with fibrosis in rats.
- Subjects
HEART beat; IVABRADINE; THYROID hormones; VENTRICULAR remodeling; LABORATORY rats; PHARMACODYNAMICS; ION channels; ECHOCARDIOGRAPHY
- Publication
Heart & Vessels, 2013, Vol 28, Issue 4, p524
- ISSN
0910-8327
- Publication type
Article
- DOI
10.1007/s00380-012-0304-z