Use this URL to cite or link to this record in EThOS:
Title: The effects of TRIAC on developing and growing rat heart muscle and its modification by certain therapeutic agents : with reference to a possible pathogenesis of hypertrophic cardiomyopathy
Author: Pearce, Peter Colin
Awarding Body: University of London
Current Institution: Imperial College London
Date of Award: 1983
Availability of Full Text:
Access from EThOS:
Access from Institution:
Hypertrophic cardiomyopathy is a heart muscle disease of unknown cause. This thesis describes a study, using the rat, which explores clinical evidence that thyroid hormones, especially their analogues, may play an important role in the pathogenesis of the disease. Triiodothyroacetic acid, triac, has been administered to pregnant rats and has produced, in the young offspring, cardiac hypertrophy and, at the ultrastructural level, an increase in the extent of myofibrillar disarray. Both of these pathological features are seen in hypertrophic cardiomyopathy in man. A series of experiments was designed to define the hitherto unknown site of action of triac. This compound was administered concurrently with selected antagonist drugs with each or all of the following activities; beta adrenergic blockade, membrane stabilisation and sympathomimetic activity. Oxprenolol, dl and d propranolol, and procainamide prevented the disarray but not the hypertrophy, and timolol had no effect. The results suggested that the most important property involved in the prevention of the action of triac was that of membrane stabilisation. A low dose of the calcium antagonist verapamil reduced both the triac induced disarray and hypertrophy, suggesting that triac may act by increasing intracellular calcium. This suggestion was supported by an experiment using the calcium ionophore A23187. This compound did not affect the action of triac, but, when administered alone, produced hypertrophy and disarray in the hearts of the offspring. An attempt was made to produce pathological features of hypertrophic cardiomyopathy, at the histological and macroscopic levels, by attempting to enhance the actions of triac so far delineated. For this purpose a beta 1 agonist, prenalterol, was used together with triac. This combination was administered to the offspring of treated rats until they were 3 months old. Severe cardiac hypertrophy was produced but not disarray. Additional experiments showed that thyroxine produced the same effects as triac but that a much higher dose was required. Triac was also given during different stages of pregnancy and was shown to be most effective during the early stage. These studies have shown the hitherto unknown site of action of triac on developing rat myocardium. They have also demonstrated how the influence of chemical and biological agents may be explored in the search for possible contributory factors in the pathogenesis of hypertrophic card iomyopathy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available