Published Online
on March 25, 2009

A more recent version of this article appeared on May 1, 2009

This Article Full Text (PDF) Data Supplement All Versions of this Article: 2/3/243    most recent CIRCHEARTFAILURE.108.810747v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Henderson, K. K. Articles by Samarel, A. M. Search for Related Content PubMed PubMed Citation Articles by Henderson, K. K. Articles by Samarel, A. M. Related Collections Congestive Cardiovascular Pharmacology Animal models of human disease Heart failure - basic studies

Original Article

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

Kyle K. Henderson^1,3; Sara Danzi²; Jennifer T. Paul¹; Greg Leya¹; Irwin Klein² and Allen M. Samarel¹

¹ Loyola University Medical Center, Maywood, Illinois;
² North Shore University Hospital, Manhasset, New York

³ E-mail: khenderson{at}lumc.edu

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 (LV) function without producing untoward signs of thyrotoxicosis.

Methods and Results—Adult male Sprague-Dawley rats were subjected to left anterior descending coronary artery ligation (MI). One week post-MI, LV fractional shortening was significantly reduced to 22±1% in CHF animals vs. 38±1% for sham-operated controls (P<0.001). Serum T₃ concentration was also significantly reduced (80±3 vs. 103±6ng/dL; P<0.001), in CHF animals vs. Shams. At 9wks post-MI, systolic function (+dP/dt max) was significantly attenuated in CHF animals (4773±259 vs. 6310±267mmHg/sec; P<0.001) as well as diastolic function measured by half time to relaxation (15.9±1.2 vs. 11.1±0.3msec; P<0.001). -Myosin heavy chain (MHC) expression was also significantly reduced by 77% (P<0.001), and β-MHC expression was increased by 21%. Continuous T₃ replacement was initiated 1wk post-MI with osmotic mini-pumps (6µg/kg/day), 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 9wks, systolic function was significantly improved by T₃ replacement (6279±347mmHg/sec; P<0.05) and a trend toward improved diastolic function (12.3±0.6msec) 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: heart failure • myocardial infarction • thyroid • Low T3 Syndrome