Time-dependent and independent effects of thyroid hormone administration following myocardial infarction in rats

Cardiac function is reduced following myocardial infarction (MI) due to myocardial injury and alterations in the viable non-ischemic myocardium, a process known as cardiac remodeling. The current treatments available for patients with acute MI (AMI) reduce infarct size, preserve left ventricular (LV) function and improve survival; however, these treatments do not prevent remodeling, which can lead to heart failure. The aim of the present study was to investigate the effects of thyroid hormone (TH) treatment following MI in an in vivo rat model. A total of 199 rats were separated into 3 groups: Sham operated and 2 different coronary artery ligation (CAL) groups. Rats subjected to CAL were randomly divided into a further 2 groups 24 h following surgery. The first group received standard rat chow (designated the CAL group), while the second group received food containing 0.05% thyroid powder (designated the CALTH group). The mean daily intake of TH per rat was estimated at 3.0 mu g T-3 and 12 mu g T-4. Echocardiography was used to monitor the rats. Large-scale analysis confirmed the favorable effects of TH treatment following CAL on various parameters of cardiac function. TH treatment reduced IX dilation, and increased global and regional LV function. The development of cardiac hypertrophy was induced and, thus, wall stress was limited. Furthermore, TH treatment improved cardiac geometry, which manifested as an increased sphericity index. Myocardial function, as well as LV dilatation, following CAL and TH treatment was not closely associated with the extent of injury, indicating a novel therapeutic intervention that may alter the course of IX remodeling that typically leads to post-MI heart failure. Data modelling and regressions may be developed to enable the simulation of the pathophysiological processes that occur following MI, and to predict with accuracy the effects of novel or current treatments that act via the modulation of tissue injury, LV dilation, LV geometry and hypertrophy.