Physiological Replacement of T3 Improves Left Ventricular Function in an Animal Model of Myocardial Infarction-Induced Congestive Heart Failure

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 mm Hg/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). alpha-myosin heavy chain expression was also significantly reduced by 77% (P<0.001), and beta-myosin heavy chain expression was increased by 21%. Continuous T-3 replacement was initiated 1 week post-myocardial infarction with osmotic mini-pumps (6 mu g/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 mm Hg/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 alpha- and reduced beta-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. (Circ Heart Fail. 2009;2:243-252.)