Physiological Replacement of T 3 Improves Left Ventricular Function in an Animal Model of Myocardial Infarction-Induced Congestive Heart Failure

Abstract

Background— Patients with congestive heart failure (CHF) often have low serum triiodothyronine (T 3 ) concentrations. In a rodent model of myocardial infarction-induced CHF and low serum T 3 , we hypothesized that replacing T 3 to euthyroid levels would improve left ventricular function without producing untoward signs of thyrotoxicosis. Methods and Results— Adult male Sprague-Dawley rats were subjected to left anterior descending coronary artery ligation (myocardial infarction). One week post-myocardial infarction, left ventricular fractional shortening was significantly reduced to 22�1% in CHF animals versus 38�1% for sham-operated controls ( P <0.001). Serum T 3 concentration was also significantly reduced (80�3 versus 103�6 ng/dL; P <0.001), in CHF animals versus Shams. At 9 weeks post-myocardial infarction, systolic function (+dP/dt max) was significantly attenuated in CHF animals (4773�259 versus 6310�267 mmHg/s; P <0.001) as well as diastolic function measured by half time to relaxation (15.9�1.2 versus 11.1�0.3 ms; P <0.001). α-myosin heavy chain expression was also significantly reduced by 77% ( P <0.001), and β-myosin heavy chain expression was increased by 21%. Continuous T 3 replacement was initiated 1 week post-myocardial infarction with osmotic mini-pumps (6 μg/kg/d), which returned serum T 3 concentrations to levels similar to Sham controls while resting conscious heart rate, arterial blood pressure and the incidence of arrhythmias were not different. At 9 weeks, systolic function was significantly improved by T 3 replacement (6279�347 mmHg/s; P <0.05) and a trend toward improved diastolic function (12.3�0.6 ms) was noted. T 3 replacement in CHF animals also significantly increased α- and reduced β-MHC expression, ( P <0.05). Conclusions— These data indicate that T 3 replacement to euthyroid levels improves systolic function and tends to improve diastolic function, potentially through changes in myocardial gene expression.