Comparison of Therapeutic Triiodothyronine Versus Metoprolol in the Treatment of Myocardial Infarction in Rats

Thyroid. 2018 Jun;28(6):799-810. doi: 10.1089/thy.2017.0544. Epub 2018 May 7.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: heart function; metoprolol; myocardial infarction; triiodothyronine.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / therapeutic use
  • Arrhythmias, Cardiac / physiopathology
  • Disease Models, Animal
  • Echocardiography
  • Electrophysiology
  • Female
  • Fibrosis
  • Heart Atria / pathology
  • Heart Ventricles / physiopathology
  • Hemodynamics
  • Inflammation
  • Metoprolol / therapeutic use*
  • Myocardial Infarction / drug therapy*
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Thyroid Hormones / blood
  • Thyroid Hormones / metabolism
  • Thyroxine / therapeutic use
  • Triiodothyronine / therapeutic use*
  • Ventricular Function, Left

Substances

  • Anti-Arrhythmia Agents
  • Thyroid Hormones
  • Triiodothyronine
  • Metoprolol
  • Thyroxine