Effects of L-thyroxine in rats with chronic heart failure after myocardial infarction

The effects of thyroid hormone on left ventricular (LV) function and myosin isoenzyme distribution were evaluated in rats 3 wk after myocardial infarction. When compared with normal rats, animals selected for study had moderately severe LV dysfunction as judged by decreased aortic and LV systolic pressures and a 34% decrease in LV maximum rate of pressure development (dP/dt). Average LV end-diastolic pressure was increased to 26 ± 1 mmHg from 5 ± 1 mmHg. The infarcted rats were divided into saline-treated control (n = 10) and treatment (n = 13) groups. The latter group received thyroxine (T₄, 1.5 μg/100 g body wt) immediately after the first determination of pressures and at 24 and 48 h. At 72 h, aortic and LV pressures and myosin isoenzyme composition were measured. In the thyroxine-treated group LV end-diastolic pressure decreased from 27 ± 2 to 18 ± 2 mmHg, and LV dP/dt increased from 5,627 ± 249 to 6,064 ± 355 mmHg/s. Heart rate and aortic pressure did not change. After saline injections, LV end-diastolic pressure remained elevated, and the other hemodynamic parameters were unchanged. Determination of ventricular myosin isoenzyme composition in the saline-treated group revealed an increase in the V₃ myosin isoform and a decrease in the V₁ isoform as compared with the normal values. This pattern was not altered by T₄ treatment. A separate group (n = 7) of rats was treated with a 10 times larger dose of thyroxine (15 μg/100 g body wt) for the same period of time. In this group, there was neither hemodynamic improvement nor changes in myosin isoenzyme distribution. Thus in this model of chronic heart failure short-term treatment with low doses of T₄ produces improvement in LV performance before changes are observed in myosin isoenzymes.