Production of cardiac muscle abnormalities in offspring of rats receiving triiodothyroacetic acid (triac) and the effect of beta adrenergic blockade.
As a part of a continuing study on the effects of thyroid hormones on heart muscle, triiodothyroacetic acid (triac), either alone or concurrently with propranolol, has been administered to rats during pregnancy. Control groups received either buffer or propranolol. Offspring, which were given no further treatment, were killed at intervals after birth and their hearts examined histologically, histochemically, and electron microscopically. At 2, 6, and 14 days, offspring of triac-treated rats showed cardiac hypertrophy and, at ultrastructural level, marked disarray of the myofibrils was present. By 28 days, arrangement of the myofibrils had become regular but hypertrophy persisted and was still found in rats examined at 56 days of age, after which time the myocardium was normal. Offspring of rats which had received propranolol at the same time as triac showed a similar pattern of hypertrophy but myofibrillar disarray was not found. Propranolol alone produced no abnormalities. These findings provide further evidence that thyroid hormone analogues can adversely affect heart muscle. When considered in conjunction with previous experiments which showed that thyroxine or triac cause severe hypertrophy but not disarray when given directly to growing rats, they suggest that thyroid hormones can produce a spectrum of abnormalities, thought to depend on the stage of myocardial development at which the stimulus is administered. In the present experiment, the triac-induced myofibrillar disarray but not the hypertrophy was prevented by propranolol, indicating that beta-adrenergic blockade or some other action of propranolol protects the developing myofibrils. Possible mechanisms for the adverse effects of thyroid hormones and the protective action of propranolol are discussed.
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000151:congenital / Q000473:pathology; D005260:Female; D006321:Heart / Q000187:drug effects; D008854:Microscopy, Electron; D009206:Myocardium / Q000648:ultrastructure; D009210:Myofibrils / Q000187:drug effects / Q000648:ultrastructure; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity
D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; D011433:Propranolol