The isolated working heart preparation was used to investigate the effect of 
continuous triiodothyronine (T3) administration on cardiac function and 
metabolism of rats rendered diabetic for a period of 4 wk with streptozocin 
(STZ). T3 controlled-release pellets were implanted 1 wk after STZ (70 mg/kg) 
injection. Rats injected with citrate buffer without STZ received T3 pellets 1 
and/or 2 wk later. A comparable number of rats received placebo pellets. 
Untreated diabetic rats exhibited a decrease in spontaneous heart rate and 
myocardial cytochrome c concentrations concurrent with depressed plasma T3 
values compared with untreated controls. T3 treatment did not improve in vitro 
cardiac performance (assessed as cardiac output times peak systolic pressure per 
gram dry heart weight) in hearts from diabetic rats perfused with glucose alone. 
Addition of octanoate reversed this depression and improved cardiac function to 
a greater extent in treated than in untreated diabetic animals. However, these 
differences between treated and untreated diabetic animals disappeared when 
heart rate was controlled by cardiac pacing. Furthermore, T3 treatment of 
controls and diabetics did not alter the oxidation of octanoate or the cardiac 
responsiveness to isoproterenol. These results suggest that experimental 
diabetic cardiomyopathy is partly attributable to a substrate deficiency and is 
not due entirely to hypothyroidism.