Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat

In a rat model of acute myocardial infarction (MI) produced by coronary art ery ligation, thyroid hormone metabolism was altered with significant reduc tions (54%) in serum triiodo-L-thyronine (T-3), the cellular active hormone metabolite. T-3 has profound effects on the heart; therefore, rats were tr eated with T-3 after acute MI for 2 or 3 wk, at either replacement or eleva ted doses, to determine whether cardiac function and gene expression could be normalized. Acute MI resulted in a 50% (P < 0.001) decrease in percent e jection fraction (% EF) with a 32-35% increase (P < 0.01) in compensatory l eft ventricle (LV) hypertrophy. Treatment of the MI animals with either rep lacement or elevated doses of T-3 significantly increased %EF to 64 and 73% of control, respectively. Expression levels of several T-3-responsive gene s were altered in the hypertrophied LV after MI, including significant decr eases in alpha -myosin heavy chain (MHC), sarcoplasmic reticulum calcium-ac tivated ATPase (SERCA2), and Kv1.5 mRNA, whereas beta -MHC and phospholamba n (PLB) mRNA were significantly increased. Normalization of serum T-3 did n ot restore expression of all T-3-regulated genes, indicating altered T-3 re sponsiveness in the postinfarcted myocardium. Although beta -MHC and Kv1.5 mRNA content was returned to control levels, alpha -MHC and SERCA2 were unr esponsive to T-3 at replacement doses, and only at higher doses of T-3 was alpha -MHC mRNA returned to control values. The present study showed that a cute MI in the rat was associated with a fall in serum T-3 levels, LV dysfu nction, and altered expression of T-3-responsive genes and that T-3 treatme nt significantly improved cardiac function, with normalization of some, but not all, of the changes in gene expression.