Consequences of thyroxine treatment on diaphragm and EDL of normal and dystrophic hamsters

Abstract

Previously administration of thyroxine (T4) to dystrophic hamsters improved ventilation and slowed the progression of the disease. We hypothesized that the normalization of ventilation in these animals was due to T4 improving structural and functional characteristics of the diaphragm. In the present study, contractile characteristics of the diaphragm and the extensor digitorum longus (EDL) from normal and dystrophic hamsters were evaluated after two months of T4 treatment. Compared to their placebo-treated counterparts, diaphragms and EDLs of T4-treated normal hamsters showed increased optimal muscle lengths and twitch tension, decreased contraction times and increased fatigability. T4-treatment in dystrophic hamsters showed only an increase in diaphragmatic twitch tension development. Force-frequency curves before treatment were generally higher for the normal compared to dystrophic diaphragms and EDLs. T4 administration only increased the force in normal diaphragms at the lower frequencies and in the EDLs at the higher frequencies. Although T4 serum levels were increased in both T4-treated groups, triiodothyronine (T3) was much lower in the dystrophic compared to normal hamsters, suggesting that conversion of T4 to T3 was reduced in dystrophic hamsters. We conclude that the limited functional changes in the diaphragms of T4-treated dystrophic hamsters cannot account for the marked improvement in ventilation previously reported.