Morphometry, histochemistry, and contractility of dystrophic hamster diaphragm

Abstract

Differences in gross and microscopic morphology, fiber-size distribution, and fiber-type composition were present in the diaphragm of 35-, 130-, and 180-day-old dystrophic (Bio 14.6) compared with age-matched control (Bio F1B) hamsters. The dystrophic diaphragm was significantly thicker than the control at 130 and 180 days. Increases in wet-to-dry weight ratios, connective tissue per unit area, and muscle fiber number suggest that increased tissue hydration, fibrosis, and fiber hyperplasia contribute to diaphragm hypertrophy. Marked variations of fiber areas and diameters were evident in each fiber type at each age, but generalized atrophy predominated over hypertrophy, resulting in significant decreases in cross-sectional areas of each fiber type. Significant differences in fiber-type composition were noted in the dystrophic vs. control diaphragm at each age: at 35 days the percentage of slow-oxidative fibers was lower and in fast-oxidative fibers was higher; at 130 days the percentage of fast-oxidative fibers remained elevated; at 180 days the percentage of fast-glycolytic fibers was reduced. In vitro contractility studies of 130-day-old animals showed that twitch and peak tension development were significantly lower in the dystrophic compared with the control diaphragm, whereas optimal length, contraction time, and half-relaxation time were within control limits. Microscopic and physiological abnormalities were also present in the soleus of 130-day-old dystrophic animals. As in the diaphragm, fiber areas were reduced, connective tissue area increased, and peak and twitch tension decreased significantly compared with the control soleus. The histopathological and pathophysiological changes in the diaphragm correlated well with each other and are consistent with the slowly evolving inability of the dystrophic hamster to increase tidal volume and minute ventilation in response to a hypercapnic challenge.

Dystropathology Increases Energy Expenditure and Protein Turnover in the Mdx Mouse Model of Duchenne Muscular Dystrophy

“…In juvenile mdx the difference is likely due to the greater hydration of dystrophic muscles [52], [53] resulting from local inflammation, myofiber necrosis, and the higher water content of newly formed fibers [54]. In the adult mdx muscle, when there is less active muscle damage and greater muscle fibrosis, TP concentration was likely underestimated by the BCA protein assay we used because it underestimates collagen by approximately 30% when albumin is used as a standard [45].…”

Animal Models of Muscular Dystrophy

“…62,63 Mice deficient in δ-SG have also been generated with subsequent complete loss of the entire SG complex, 64,65a and as with the BIO14.6 hamster, these mice display classical histological findings of dystrophy inclusive of muscle degeneration, necrosis, inflammation, fibrosis, and reduced survival. However, muscle mass, peak twitch tension ( P 1 ) and peak tetanic tension ( P 0 ), and specific force ( P 0 /CSA) do not differ from wild-type muscle with the latter being in contrast to the BIO14.6 hamster 65b suggesting species-specific variations in pathophysiology. Similar to the BIO14.6 hamster model, these mice develop cardiomyopathy with a relatively early onset (∼ 8 weeks) with areas of fibrosis.…”

Deficiency of α-sarcoglycan differently affects fast- and slow-twitch skeletal muscles

“…Soleus muscle of dystrophic hamster equally showed the dramatic decrease of specific tensions (7). In contrast to the Bio 14.6 dystrophic hamster, mice lacking ␦-sarcoglycan showed no changes in the absolute tetanic force produced by EDL (23).…”