Abstract
In the field of muscular dystrophy, striated muscle function is often assessed in vitro in dystrophin-deficient mdx mice in order to test the impact of a potential treatment strategy. Although many past studies have assessed diaphragm contractile function at or near room temperature, the diaphragm performs in vivo at 37°C. To improve translation of bench-top results to possible clinical application, we studied temperature-dependence of contractile performance in wild-type (C57BL/10) and mdx muscle strips at temperatures from 25°C to 37°C. Maximal tetanic force in wild-type muscles was higher at 37°C (198 ± 11 vs. 155 ± 9 mN/mm2 at 25°C), while the difference between wild-type and mdx was extremely similar: wild-type muscles produced 45.9% and 45.1% more force at 25°C and 37°C respectively. At 37°C twitch contraction kinetics and 50% rise time to tetanic plateau were slower in mdx diaphragm. A fatigue/injury protocol indicated 2-fold fatigue/contraction-induced force deficit in mdx muscles. We conclude that assessment of diaphragm muscle strips can be reliably and reproducibly performed at 37°C.
Highlights
Duchenne muscular dystrophy (DMD) is an X-linked disorder that affects males and is characterized by muscle degeneration and weakness
We found that the forces generated at body temperature by the wild-type and mdx diaphragm were slightly higher and developed drastically faster than at room temperature for both mouse strains
Data were collected from 16 C57BL/10 mice and 10 mdx mice with two muscle strips taken from each diaphragm
Summary
Duchenne muscular dystrophy (DMD) is an X-linked disorder that affects males and is characterized by muscle degeneration and weakness. This disease results in death by the third decade of life due to cardiac and respiratory complications (Emery, 2002). There exists some degree of irregularity when comparing reported values relating to contractile function of isolated diaphragm muscle, especially among observed tetanic force measurements in healthy control mice, mdx mice, as well as other models of DMD. We present an argument for revising SOPs involving mouse diaphragm muscle to be preferably performed at 37◦C
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