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 (T3) concentrations. In a rodent model of myocardial infarction-induced CHF and low serum T3, we hypothesized that replacing T3 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 T3 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). &agr;-myosin heavy chain expression was also significantly reduced by 77% (P<0.001), and &bgr;-myosin heavy chain expression was increased by 21%. Continuous T3 replacement was initiated 1 week post-myocardial infarction with osmotic mini-pumps (6 &mgr;g/kg/d), which returned serum T3 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 T3 replacement (6279±347 mm Hg/s; P<0.05) and a trend toward improved diastolic function (12.3±0.6 ms) was noted. T3 replacement in CHF animals also significantly increased &agr;- and reduced &bgr;-MHC expression, (P<0.05). Conclusions—These data indicate that T3 replacement to euthyroid levels improves systolic function and tends to improve diastolic function, potentially through changes in myocardial gene expression.

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