Background: This study aimed to evaluate the effects of irbesartan, a renin-angiotensin system (RAS) blocking agent and dronedarone, which blocks multiple cardiac ion channels and β-adrenoceptors, on the functional and structural manifestations of experimental hyperthyroid cardiomyopathy.
Methods: A rat model of hyperthyroidism was established by daily intraperitoneal injections of L-thyroxine (T4, 100 µg/kg per day) for 28 days. Forty Sprague-Dawley rats were randomly divided into four groups (n = 10 each): control group, T4 group (T4 alone), T4 plus irbesartan group (T4-Irb, 30 mg/kg irbesartan), and T4 plus dronedarone group (T4-Dro, 100 mg/kg dronedarone). All rats underwent echocardiography and cardiac chamber size and strain parameters were measured after 28 days treatments. Cardiomyocyte diameter and cardiac fibrosis were measured using pathological analysis.
Results: Heart rate was increased in T4 alone and T4-Irb groups. When compared with control, T4 alone showed significantly reduced ejection fraction (EF; 72.11±5.49 vs. 77.63±5.01 %., P<0.05) and LV longitudinal strain (LV strain; -15.97 ± 6.27 vs. -22.73 ± 5.19 %, P<0.05). However, compared with control, T4-Irb showed similar EF (77.60±3.85 %.) and LV strain (-21.41 ± 1.84 %). Morphologically, T4 alone showed significantly increased cardiomyocyte width (25.3 ±1.89 vs. 18.90± 1.14 μm in control, P<0.001) and fibrosis, which is prevented by irbesartan treatment (cardiomyocyte width; 18.90± 1.14 vs. 25.3 ±1.89 μm in T4 alone, P<0.05). Although T4-Dro showed no significant reduction in cardiomyocyte width and fibrosis compared with T4 alone, EF and LV strain was improved compared with T4 alone.
Conclusions: Irbesartan could significantly attenuate structural and functional remodeling induced by experimental hyperthyroid cardiomyopathy, which is not found with dronedarone although regulation of heart rate. Our result may implicate the potent role of RAS in hyperthyroid cardiomyopathy beyond tachycardia.
Key Words: Cardiomyopathy, Hyperthyroidism, Renin-angiotensin system, Echocardiography
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