The possibility that thyroid hormone or a thyroid hormone analogue that improves 
cardiac performance might be useful in the treatment of heart failure has-been 
examined. In the rat postinfarction model of heart failure, treatment with low 
doses (1.5 micrograms/100 g) of thyroxine (T4) for 3 days produced a positive 
inotropic response, including an increase in left ventricular (LV) dP/dt and a 
decrease in LV end-diastolic pressure (LVEDP). When treatment with T4 was 
continued at the same or higher doses (3 to 15 micrograms/100 g) for 10-12 days, 
heart rate was increased and improvement in LVEDP was not sustained. To identify 
an analogue with a more favorable hemodynamic profile, single- and double-ring 
compounds related to T4 were screened for thyromimetic activity in heart cell 
cultures and for their ability to bind thyroid hormone receptors. One of the 
analogues selected, 3,5-diiodothyropropionic acid (DITPA), was found to have 
inotropic selectivity in hypothyroid rats. When administered (375 micrograms/100 
g) to rats with ventricular dysfunction after myocardial infarction in 
combination with captopril, there was improvement of the resting and stressed 
cardiac index and LV filling pressure. Similar improvement in cardiac 
performance was obtained when DITPA was administered to rabbits after 
infarction. Thus a thyroid hormone analogue with inotropic selectivity may be a 
useful adjunct to other measures in the treatment of heart failure.