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Heart rate reduction with ivabradine prevents thyroid hormone-induced cardiac remodeling in rat.
MedLine Citation:
PMID:  23142972     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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(4), 100 μg/kg/day), and injection of L-thyroxine with ivabradine (T(4)-Iva, T(4) + 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 T(4) 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 SR(circ), S (long) and SR(long) in the T(4) group, and the average I (Ca,L) density at 0 mV in T(4)-Iva groups (9.9 ± 1.6 pA/pF) was restored to the control level. Morphologically, the T(4) 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(2+) handling without modification of the myocyte hypertrophy with fibrosis in rats.
Authors:
Bo Hyun Kim; Kyoung Im Cho; Seong Man Kim; Nari Kim; Jin Han; Jee Yeon Kim; In Ju Kim
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-11
Journal Detail:
Title:  Heart and vessels     Volume:  -     ISSN:  1615-2573     ISO Abbreviation:  Heart Vessels     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8511258     Medline TA:  Heart Vessels     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea.
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