T3 treatment does not prevent myocardial dysfunction in chronically diabetic rats.
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.
Barbee
R W
RW
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Shepherd
R E
RE
Burns
A H
AH
D000818:Animals; D002210:Caprylates / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D006207:Half-Life; D006331:Heart Diseases / Q000209:etiology / Q000517:prevention & control*; D006339:Heart Rate; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000627:therapeutic use*
D002210:Caprylates; D003574:Cytochrome c Group; D014284:Triiodothyronine; D007545:Isoproterenol; C031492:octanoic acid