Background: Resting sinus tachycardia is the most common cardiovascular sign of human hyperthyroidism, but there are rare studies showing the pathophysiology of heart failure occurred in hyperthyroidism. The aim of this study was to investigate the alterations of left ventricular (LV) function and ion channel activity, and structural remodeling affecting cardiac performance during hyperthyroidism. Furthermore, we evaluated the effect of ivabradine on these manifestigations of hyperthyroid cardiomyopathy. Methods: Thirty Sprague-Dawley rats were randomly selected to receive an injection of L-thyroxine (T4, 100 µg/kg/day) or L-thyroxine with ivabradine (T4-Iva, T4+100 mg/kg/day), or an equal volume of 0.9% saline (control, 1 mL/kg/day). Circumferential (Scirc), radial (Srad) and longitudinal (Slong) strain were assessed by speckle tracking echocardiography (STE). Myocardial width and fibrosis was assessed from histological LV cross sections, and electrophysiological analysis was done by patch clamp method. Results: Compared with control group, T4 group showed significantly increased heart rate and end-systolic LV diameter, 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 average ICa,L density at 0 mV in T4 groups (13.4±1.2 pA/pF, n=6) was increased by 59.5% from the value in control groups (8.4±0.8 pA/pF, n=5). Morphologically, T4 group showed significantly increased cardiomyocyte width (25.3 ±1.89 vs. 18.90± 1.14 μm in control, P<0.001) and fibrosis. T4-Iva group showed no differences in heart rate compared with control (376.60±36.64 vs. 408.25±33.25, P <0.01) and the average ICa,L density at 0 mV in T4-Iva groups (9.9±1.6 pA/pF, n=6) was restored to control level. Also T4-Iva showed increased SRcirc , Slong and SRlong compared with T4 group although no significant change in microscopic analysis. Conclusion: Altered cardiac contractility due to cellular level of electrophysiologic change and pathologic hypertrophy with enhanced fibrosis might be induced by excess thyroid hormone. Heart rate lowering treatment may prevent myocardial dysfunction by suppression of the hemodynamic manifestations of hyperthyroidism without modification of the morphologic alterations of hyperthyroid rats, indicating specificity in the pathogenesis in hyperthyroid cardiomyopathy beyond tachycardia.
Key Words: thyroid hormone; heart failure; pathophysiology
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