Published online before print March 25, 2009, doi: 10.1161/CIRCHEARTFAILURE.108.810747
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Original Articles |
Physiological Replacement of T3 Improves Left Ventricular Function in an Animal Model of Myocardial Infarction-Induced Congestive Heart Failure
From the Department of Medicine and the Cardiovascular Institute (K.K.H., J.T.P., G.L., A.M.S.), Loyola University Medical Center, Maywood, Ill; and Department of Medicine and the Feinstein Institute for Medical Research (S.D., I.K.), North Shore University Hospital, Manhasset, NY.
Correspondence to Kyle K. Henderson, PhD, Bldg No. 110; Room No. 5227, Cardiovascular Institute, Loyola University Medical Center, 2160 South First Ave, Maywood, IL 60153. E-mail khenderson{at}lumc.edu
Received July 29, 2008; accepted February 27, 2009.
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 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). 
-myosin heavy chain expression was also significantly reduced by 77% (P<0.001), and β-myosin heavy chain expression was increased by 21%. Continuous T3 replacement was initiated 1 week post-myocardial infarction with osmotic mini-pumps (6 µg/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 mmHg/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 - and reduced β-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.
Key Words: myocardial infarction • heart failure • thyroid • low T3 syndrome