T3 improves left ventricular function in a rodent model with a myocardial infarction

Abstract

Serum triiodothyronine (T3) concentration is reduced in patients with congestive heart failure which may contribute to the altered expression of thyroid hormoneresponsive genes. We hypothesize that T3 supplementation in a rat model of left ventricular (LV) dysfunction will increase α/β myosin heavy chain (MHC) ratio, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) expression, and thereby improve LV function. Echocardiography was used to assess LV structure and function in male Sprague Dawley rats (~300g), before and after left anterior descending coronary artery ligation. One week post‐ligation, LV function was significantly attenuated; ejection fraction was reduced from 38±1% to 21±1%. Saline control or T3 supplementation was then started at 3, 6 and 60μg/kg/day for 8wks. Radiotelemetry was used to measure body temperature, ECG, and arterial blood pressure in a subset of animals. LV structure and function, at 2, 4, 6 and 8wks were not changed by T3 supplementation as measured by echocardiography. However, LV catheterization at 8wks demonstrated that animals receiving T3 supplementation at 6 or 60μg/kg/day had significantly greater LV contractility (+dP/dt) and a trend toward improved LV relaxation (Tau). LV RNA was extracted for measurement of α and β MHC and SERCA mRNA. These findings support the hypothesis that T3 supplementation may improve the function of the remaining viable LV tissue in rats with a myocardial infarction. Funding: Ralph and Marian Falk Medical Research Trust and King Pharmaceuticals.