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Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac remodeling in rat

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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 μg/kg/day), and injection of l-thyroxine with ivabradine (T4-Iva, T4 + 10 mg/kg/day). Circumferential (S circ), radial (S rad), and longitudinal (S long) 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 T4 group showed significantly increased HR and LV end-systolic diameter (LVESD), reduced S circ (−16.04 ± 3.95 vs. −7.84 ± 2.98 %, p < 0.001), S rad (20.94 ± 3.81 vs. 40.57 ± 6.70 %, p < 0.001), and S long (−15.26 ± 5.15 vs. −23.83 ± 5.19 %, p < 0.001), despite the 59.5 % increase of average I Ca,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, S long and SRlong in the T4 group, and the average I Ca,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 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 Ca2+ handling without modification of the myocyte hypertrophy with fibrosis in rats.

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Acknowledgments

The authors declare that no competing financial interests exist.

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Authors and Affiliations

  1. Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea

    Bo Hyun Kim & In Ju Kim

  2. Division of Cardiology, Department of Internal Medicine, Maryknoll Medical Center, Daecheong Dong 4-ga, Jung-gu, Busan, Korea

    Seong Man Kim

  3. National Research Laboratory for Mitochondrial Signaling, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea

    Nari Kim & Jin Han

  4. Department of Pathology, Pusan National University School of Medicine, Busan, Korea

    Jee Yeon Kim

  5. Biomedical Research Institute, Pusan National University, Busan, Korea

    Bo Hyun Kim & In Ju Kim

  6. Division of Cardiology, Department of Internal Medicine, Kosin University School of Medicine, 34 Amnam-Dong, Seo-Ku, Busan, 602-702, Korea

    Kyoung Im Cho

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Correspondence to Kyoung Im Cho.

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Kim, B.H., Cho, K.I., Kim, S.M. et al. Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac remodeling in rat. Heart Vessels 28, 524–535 (2013). https://doi.org/10.1007/s00380-012-0304-z

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