Alveolar hypoventilation (AH) occurs when the elimination of metabolic CO2 is outpaced by its production. It is a common feature of neuromuscular disease that leads to cardiac and skeletal muscle dysfunction. The BIO 14.6 hamster (DH) is a useful animal model that displays AH. Studies indicate that DH display pathological changes in the gross and microscopic morphology, histochemistry, cation content and contractility in the diaphragm, which are consistent with the slowly evolving inability of the animal to increase tidal volume and minute ventilation in response to a hypercapnic challenge. AH is also associated with low serum levels of triiodothyronine (T3) and thyroxine (T4). The investigators recently showed that T4 treatment slows down the progression of dystrophic features in DH and improves ventilatory responses to hypoxia and hypercapnia. The purpose of this project is to determine whether T4 replacement in DH improves ventilation by preventing morphological degeneration and histochemical changes in the diaphragm and how these changes correlate with serum thyroid hormone levels, cation content and improved contractility.
|Singh, Yadhu N; Schlenker, Evelyn H; Singh, Brahma N et al. (2004) Consequences of thyroxine treatment on diaphragm and EDL of normal and dystrophic hamsters. Can J Physiol Pharmacol 82:345-52|