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.


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). 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 microg/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 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.
Henderson
Kyle K
KK
Department of Medicine and the Cardiovascular Institute, Loyola University Medical Center, Maywood, Ill 60153, USA. khenderson@lumc.edu
Danzi
Sara
S
Paul
Jennifer T
JT
Leya
Greg
G
Klein
Irwin
I
Samarel
Allen M
AM
D000818:Animals; D001794:Blood Pressure; D003971:Diastole; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006339:Heart Rate; D020249:Hormone Replacement Therapy; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D015918:Infusion Pumps, Implantable; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D018995:Myosin Heavy Chains / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013599:Systole; D013997:Time Factors; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D024723:Ventricular Myosins / Q000235:genetics
D012333:RNA, Messenger; D014284:Triiodothyronine; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains