Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats

Abstract

Objective: Cardiac remodeling of viable myocardium occurs after acute myocardial infarction (AMI) and further contributes to cardiac dysfunction. The present study explored whether thyroid hormone (TH) administered shortly after AMI in rats can attenuate cardiac remodeling and improve cardiac function. TH regulates important structural and regulatory proteins in the myocardium including myosin isoform expression and calcium cycling proteins. Methods: AMI was induced in Wistar male rats by ligating left coronary artery (AMI, n = 10), while sham-operated rats were used as controls (SHAM, n = 10). Animals with acute myocardial infarction were also treated with 0.05% thyroid powder in food (AMI-THYR, n = 10). Within 2 weeks, cardiac function was impaired as assessed by echocardiography and under isometric conditions in Langendorff preparations. Results: Ejection fraction (EF%) was 71.5 (SEM, 2.7) in SHAM versus 30.0 (2.0) in AMI, P < 0.05. +dp/dt was 3886 (566) in SHAM versus 2266 (206) in AMI hearts, P < 0.05 and -dp/dt was 1860 (46) in SHAM versus 1633 (120) in AMI hearts, P = ns. Such changes were associated with alterations in myosin isoform expression in the non-infarcted area; AMI hearts expressed 34% α-MHC and 66% β-MHC versus 52% α-MHC and 48% β-MHC in SHAM, P < 0.05, while the expression of SERCA and phospholamban (PLB) remained unchanged. Furthermore, a mismatch of left ventricular size and cardiac mass (2*Posterior Wall thickness/LVIDd was decreased) was observed. After TH treatment, AMI-THYR hearts expressed 71% α-MHC and 29% β-MHC, P < 0.05 versus SHAM and AMI and the ratio of SERCA/PLB was increased by 2.0-fold, P < 0.05 versus SHAM and AMI. These changes corresponded to a marked improvement in cardiac function; EF% was raised to 45.8 (1.7), P < 0.05 versus AMI while +dp/dt and -dp/dt were 3800 (435) and 2600 (200), respectively, in AMI-THYR hearts, P < 0.05 versus AMI. The ratio of 2*Posterior Wall thickness/LVIDd was normalized. Conclusions: Thyroid hormone administration early after infarction attenuates cardiac remodeling and significantly improves myocardial performance. © 2007 European Association for Cardio-Thoracic Surgery.