Document Type

Thesis - University Access Only

Award Date

1997

Degree Name

Master of Science (MS)

Department / School

Pharmaceutical Sciences

Abstract

The BIO 14.6 dystrophic hamster is a genetically determined animal model which exhibits muscular dystrophy. A possible contribution to this hereditary myopathy is made by an abnormal metabolism of thyroxine hormone which plays an important role in metabolism, neural activity, muscle strength, and lung diffusion capacity. The purpose of this investigation was to test the hypothesis that thyroxine treatment started in young dystrophic hamsters improves skeletal muscle functions by preventing or reducing the development of morphological and contractile degeneration in skeletal muscles. The experimental protocol included 3 test groups of animals: Normal (BIO F 1 B) (placebo treated), dystrophic (placebo treated), and dystrophic (thyroxine treated). Normal and dystrophic placebo groups were implanted s.c. with placebo pellets containing biodegradable carrier-binder, while the dystrophic thyroxine treated group received 90- day, 22 mg L-thyroxine pellets, also s.c; the implantation was repeated after 3 months for the 6-month experimental groups. Various contractile and morphometric characteristics were evaluated on the phrenic nerve-hemidiaphragm preparations and extensor digitorum longus (EDL) muscles isolated from normal and dystrophic hamsters, pretreatment and after 2 months and 6 months post-treatment. After thyroxine supplementation, the body weight gain in DT group was significantly higher (P<0.05) compared to DP group;-from 7 to 18 weeks. Nonsignificant increases in optimal muscle length (Lo) were observed in diaphragm of DT, both after 2 month and 6 month post-treatment; the increase was more after 2 month post-treatment. In contrast, no significant difference (P>0.05) in Lo was observed between DP and DT groups after 2 month and 6 month post-treatment, which is consistent with earlier findings in dystrophic animals that limb muscles are slowly and less affected by muscular dystrophy. A significantly higher (P<0.05) muscle weight of diaphragm for DP compared to NP could be attributed to increased tissue hydration and calcification indystrophic skeletal muscles. The increased tissue hydration was also reflected in terms of lower (P<0.05) % dry-to-wet weight ratios for DP compared to NP. Similar to Lo, a nonsignificant increase (P>0.05) in diaphragm weight was observed in DT group, after 2 month and 6 month post-treatment, the increase being more after 2 month post-treatment. The values of twitch tension (specific force) were significantly lower (P<0.05), both in direct and indirect modes, for DP compared to NP at all the time points. Further, an increase in this force was observed in DT compared to DP; the increase was significant (P<0.05) after 2 month post-treatment (in direct mode) and 6 month post-treatment (in indirect mode). Also, a significant increase (P<0.05) was observed in EDL muscle of DT group after 2 month post-treatment. The maximum tetanic force occurred at frequencies between 80- 100 Hz. Nonsignificant increases (P>0.05) in maximum tetanic force (prefatigue and postfatigue) were observed in DT group after 2 month and 6 month post-treatment, both in DIA and EDL ; the increase was significant for directly stimulated EDL at t=2 months. No significant difference (P>0.05) was observed between twitch contraction times for DIA of DP and DT groups, after 2 month and 6 month post-treatment. On the other hand, twitch half-relaxation times were insignificantly reduced (P>0.05) in dystrophic DIA, both in direct and indirect modes, after 2 month and 6 month post-treatment. The slowing of time course of twitch has been ascribed to the decrease in activity of sarcoplasmic reticulum Ca2+-ATPase by thyroid hormone deficiency, suggesting a slowed Ca2+ re-uptake and therefore a slowed relaxation time course. Similar reductions in fatigue resistance of dystrophic DIA and EDL muscles were observed in DT group after 2 months and 6 months of thyroxine treatment; the reduction was significant (P<0.05) for DIA-direct mode at t=6 months. Our morphometric and contractile data correlate well with the severe and progressive nature of muscular dystrophy, especially after 2 month post-treatment. The results of this study also suggest that thyroxine therapy may be beneficial in dystrophic hamsters, if started early in their life span.

Library of Congress Subject Headings

Muscular dystrophy -- Treatment
Thyroxine
Hamsters -- Physiology

Format

application/pdf

Number of Pages

139

Publisher

South Dakota State University

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