Abstract

Leg muscle ischemia in patients with peripheral artery disease (PAD) leads to alterations in skeletal muscle morphology and reduced leg strength. We tested the hypothesis that exposure to heat therapy (HT) would improve skeletal muscle function in a mouse model of ischemia-induced muscle damage. Male 42-wk-old C57Bl/6 mice underwent ligation of the femoral artery and were randomly assigned to receive HT (immersion in a water bath at 37°C, 39°C, or 41°C for 30 min) or a control intervention for 3 wk. At the end of the treatment, the animals were anesthetized and the soleus and extensor digitorum longus (EDL) muscles were harvested for the assessment of contractile function and examination of muscle morphology. A subset of animals was used to examine the impact of a single HT session on the expression of genes involved in myogenesis and the regulation of muscle mass. Relative soleus muscle mass was significantly higher in animals exposed to HT at 39°C compared with the control group (control: 0.36 ± 0.01 mg/g versus 39°C: 0.40 ± 0.01 mg/g, P = 0.024). Maximal absolute force of the soleus was also significantly higher in animals treated with HT at 37°C and 39°C (control: 274.7 ± 6.6 mN; 37°C: 300.1 ± 7.7 mN; 39°C: 299.5 ± 10 mN, P < 0.05). In the soleus, but not the EDL muscle, a single session of HT enhanced the mRNA expression of myogenic factors as well as of both positive and negative regulators of muscle mass. These findings suggest that the beneficial effects of HT are muscle specific and dependent on the treatment temperature in a model of PAD. NEW & NOTEWORTHY This is the first study to comprehensively examine the impact of temperature and muscle fiber type composition on the adaptations to repeated heat stress in a model of ischemia-induced muscle damage. Exposure to heat therapy (HT) at 37°C and 39°C, but not at 41°C, improved force development of the isolated soleus muscle. These results suggest that HT may be a practical therapeutic tool to restore muscle mass and strength in patients with peripheral artery disease.

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