Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac remodeling in rat
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ORIGINAL ARTICLE
Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac remodeling in rat Bo Hyun Kim • Kyoung Im Cho • Seong Man Kim Nari Kim • Jin Han • Jee Yeon Kim • In Ju Kim
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Received: 8 June 2012 / Accepted: 19 October 2012 / Published online: 11 November 2012 Ó Springer Japan 2012
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 (T4, 100 lg/kg/day), and injection of L-thyroxine with ivabradine (T4-Iva, T4 ? 10 mg/kg/day). Circumferential (Scirc), radial (Srad), and longitudinal (Slong) strains were assessed by speckle tracking echocardiography (STE). Myocardial width and fibrosis were B. H. Kim I. J. Kim Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea B. H. Kim I. J. Kim Biomedical Research Institute, Pusan National University, Busan, Korea K. I. Cho (&) Division of Cardiology, Department of Internal Medicine, Kosin University School of Medicine, 34 Amnam-Dong, Seo-Ku, Busan 602-702, Korea e-mail: [email protected] S. M. Kim Division of Cardiology, Department of Internal Medicine, Maryknoll Medical Center, Daecheong Dong 4-ga, Jung-gu, Busan, Korea N. Kim J. Han National Research Laboratory for Mitochondrial Signaling, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea J. Y. Kim Department of Pathology, Pusan National University School of Medicine, Busan, Korea
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assessed from histological LV cross sections, and electrophysiological analysis was done by patch clamp method. In comparison with the control group, the T4 group showed significantly increased HR and LV end-systolic diameter (LVESD), reduced Scirc (-16.04 ± 3.95 vs. -7.84 ± 2.98 %, p \ 0.001), Srad (20.94 ± 3.81 vs. 40.57 ± 6.70 %, p \ 0.001), and Slong (-15.26 ± 5.15 vs. -23.83 ± 5.19 %, p \ 0.001), despite the 59.5 % increase of average ICa,L 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 SRcirc, Slong and SRlong in the T4 group, and the average ICa,L density at 0 mV in T4-Iva groups (9.9 ± 1.6 pA/pF) was restored to the control level. Morphologically, the T4 group showed significantly increased cardiomyocyte width (25.3 ± 1.89 vs. 18.90 ± 1.14 lm in control, p \ 0.001) and fibrosis, which were not significantly changed by ivabradine. In conclusion, selective HR reduction by ivabradine attenuates thyroid hormoneinduced reduction of myocardial deformation and altered intracellular Ca2? handling without modification of the myocyte hypertrophy with fibrosis in rats. Keywords Thyroid hormone Heart failure Echocardiography Electrophysiology
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