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Effects of Hypothyroidism and Menopause on Cardiac Repair in Female Rats Post-Myocardial Infarction
Background Sex-specific research dealing with the impacts of the endocrine system and menopause on the cardiovascular health of women is essential. In this work, we assess the effects of hypothyroidism and menopause on physiologic metrics (i.e. weight, temperature), blood pressure, cardiac function (i.e. ejection fraction, cardiac output), and degree of hypertrophy (i.e. myocyte size, heart weight) in a female rodent model of heart failure. This study aims to harness the positive cardioprotective effects of thyroid hormones and estrogen to identify heart failure treatment strategies and improve the heart health of women.
Methods We examine the difference in cardiac repair responses to exogenous administration of triiodothyronine (T3), 3,3’-diiodothyronine (3,3′-T2), and estrogen (E2) in hypothyroid, postmenopausal female rats that have surgically induced myocardial infarctions (MI) via permanent ligation of the Left Anterior Descending (LAD) artery. Hypothyroidism was induced via daily propylthiouracil (PTU) administration (1 mg/mL in their drinking water), and menopausal state induced surgically via ovariectomy (OVX). Rats were weighed daily, and blood pressure, thyroid hormone levels, and temperature were monitored weekly for 9 weeks. Echocardiograms and electrocardiograms were performed pre- and post-LAD ligation to confirm MI, establish exclusion criteria, and evaluate differences in cardiac function. Rat hearts and thyroids were harvested, weighed, and stained using H&E and Picrosirius Red to assess for hypertrophy. Serum was analyzed for T3, T4, and TSH using a Luminex Assay to determine the effects of exogeneous hormone replacement therapy on endogenous hormone levels.
Results PTU administration resulted in significant reductions in rodent body weight and temperature as well as thyroid gland size. Blood pressure measurements showed a significant reduction in pulse in the hypothyroid rats. After MI, both euthyroid and hypothyroid rats experienced similar levels of decreased cardiac function. However, while T3 treatment resulted in a lower left ventricular ejection fraction (LVEF) % in euthyroid rats compared to saline and 3,3’-T2 treated rats, in hypothyroid rats it resulted in a higher LVEF%. Cardiac output was higher when hypothyroid rats were treated with T3 when compared to saline and 3,3’-T2 treatment.
Conclusion We show that T3, in the euthyroid status has a detrimental effect, decreasing LVEF while in the hypothyroid status improves LVEF. Therefore, administration of thyroid hormones in hypothyroid individuals could be used productively for the treatment of heart failure, despite current contraindications. This study will evaluate if underlying estrogen hormone imbalances affect cardiac repair and better determine any confounding effects when administered with thyroid hormones.