1 Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases , Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China .
2 Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic Medicine , Old Westbury, New York.
Thyroid. 2018 Jun;28(6):799-810. doi: 10.1089/thy.2017.0544. Epub 2018 May 7.
Beta blockers are standard therapy for myocardial infarction (MI). Preclinical studies have shown efficacy and safety of thyroid hormone (TH) treatment of cardiovascular disorders. Since THs interact with the sympathoadrenergic system, this study aimed to compare triiodothyronine (T3) and metoprolol (Met) in the treatment of rats with MI on pathophysiology and TH-adrenergic signaling.
Female Sprague-Dawley rats aged 12 weeks underwent left anterior descending coronary artery ligation (MI) or sham surgeries. T3 (5 μg/kg/day) or Met (100 mg/kg/day) was given in drinking water immediately after surgery for eight weeks. At the terminal of the experiments, the rats were subjected to morphological, functional, and molecular examination.
T3 and Met significantly enhanced left ventricular contractility (left ventricular fractional shortening 21.37 ± 2.58% and 21.14 ± 3.71%, respectively) compared to untreated MI (17.88 ± 1.23%), and decreased the incidence of inducible atrial tachyarrhythmia by 87.5% and 62.5%, respectively. Although both treatments showed efficacy, T3 but not Met showed statistically significant improvements compared to MI in arrhythmia duration, left atrial diameter (T3 vs. MI 4.33 ± 0.63 vs. 5.65 ± 1.32 mm; p < 0.05), fibrosis (6.1 ± 0.6%, 6.6 ± 0.6% vs. 8.2 ± 0.7%, T3, Met vs. MI, respectively), and aortic vasorelaxation responsiveness to acetylcholine (pD2 6.97 ± 0.22, 6.83 ± 0.21 vs. 6.66 ± 0.22, T3, Met vs. MI, respectively). Quantitative polymerase chain reaction showed that T3 and Met attenuated expression of genes associated with inflammation and oxidative stress and restored expression of ion channels and contractile proteins.
These results support comparable efficacy of T3 and Met treatments, suggesting that T3 may provide a therapeutic alternative to standard β-receptor blockade, especially for patients intolerant to treatment with β-blockers after MI.
β受体阻滞剂是心肌梗死（MI）的标准治疗方法。临床前研究表明甲状腺激素（TH）治疗心血管疾病的疗效和安全性。由于 TH 与交感神经系统相互作用，因此本研究旨在比较三碘甲状腺原氨酸（T3）和美托洛尔（Met）在 MI 大鼠的病理生理学和 TH-肾上腺素能信号方面的治疗作用。
12 周龄雌性 Sprague-Dawley 大鼠进行左前降支冠状动脉结扎（MI）或假手术。手术后立即在饮用水中给予 T3（5μg/kg/天）或 Met（100mg/kg/天），持续 8 周。在实验的末期，对大鼠进行形态学、功能和分子检查。
与未治疗的 MI（17.88±1.23%）相比，T3 和 Met 可显著增强左心室收缩力（左心室短轴缩短率分别为 21.37±2.58%和 21.14±3.71%），并分别降低 87.5%和 62.5%的可诱导性房性心动过速发生率。尽管两种治疗方法均有效，但与 MI 相比，T3 而非 Met 在心律失常持续时间、左心房直径（T3 与 MI 分别为 4.33±0.63 与 5.65±1.32mm；p<0.05）、纤维化（6.1±0.6%、6.6±0.6%与 8.2±0.7%，T3、Met 与 MI，分别）和乙酰胆碱诱导的主动脉血管舒张反应性（pD2 分别为 6.97±0.22、6.83±0.21 与 6.66±0.22，T3、Met 与 MI，分别）方面显示出统计学意义上的显著改善。定量聚合酶链反应显示，T3 和 Met 可减轻与炎症和氧化应激相关的基因表达，并恢复离子通道和收缩蛋白的表达。
这些结果支持 T3 和 Met 治疗的等效疗效，表明 T3 可能为标准β受体阻滞剂治疗提供替代治疗方法，特别是对 MI 后不耐受β受体阻滞剂治疗的患者。
