Impact of Heat Therapy on Skeletal Muscle Mass and Function in A Mouse Model of Duchenne Muscular Dystrophy

Abstract

BackgroundDuchenne muscular dystrophy (DMD) is a lethal X‐linked degenerative disease that is characterized by progressive skeletal muscle wasting and weakness. Few non‐invasive and widely available therapies currently exist to combat the skeletal muscle abnormalities in patients with DMD. Repeated exposure to heat therapy (HT) has been shown to attenuate skeletal muscle atrophy during immobilization and unloading, rescue denervation‐induced atrophy, and increase relative muscle mass and strength in models of ischemia‐induced muscle damage. The goal of the present study was to test the hypothesis that repeated exposure to HT would enhance skeletal muscle mass and contractile function in D2‐mdx mice, a model that recapitulates several of the human characteristics of DMD.MethodsMale D2‐mdx and wild‐type DBA/2J mice (8 weeks of age) were obtained from the Jackson Laboratory. In study 1, we sought to define the optimal temperature for HT application using a heat incubator. Male DBA/2J mice (n=24) were randomly allocated to a control group or one of three different HT regimens (37, 39, 41℃). The treatment regimen consisted of exposure to HT for 30 min/day, 5 days/week during 3 consecutive weeks. Mice assigned to the control group underwent a similar intervention, but the incubator was maintained at room temperature. Based upon the findings of the first experiment, the goal of study 2 was to examine the effects of daily HT at 39℃ for 3 weeks on skeletal muscle mass and function in D2.mdx mice. Twenty‐four D2.mdx mice were randomized to either a HT group (n=12) or a control group (n=12) and were treated as described in study 1. Approximately 48 hrs after the last treatment session, the soleus and extensor digitorum longus (EDL) muscles were isolated and harvested for the measurement of wet mass and the assessment of contractile function.ResultsIn study 1, DBA/2J mice exposed to HT at 39ºC, but not 37º or 41ºC, displayed an increase in relative muscle mass (the ratio of muscle mass to body weight) of both EDL (p=0.03) and soleus (p=0.02) muscles when compared to the control group. Moreover, the EDL maximal specific force was greater in animals treated with HT at 39ºC relative to the 41℃ group (p=0.01). There were no significant differences between groups in soleus muscle force development. In study 2, D2.mdx mice exposed HT at 39ºC tended to display greater relative EDL muscle mass when compared to the control group (p=0.06). However, the relative mass of the soleus muscle was similar between the group treated with HT and the control regimen (p=0.84). The maximal force of both EDL and soleus muscles was also comparable between treated animals and the control group.ConclusionsOur findings indicate that exposure to HT at 39℃ for 3 weeks has limited effects on skeletal muscle mass and strength in a mouse model of DMD. Additional studies are warranted to determine whether different treatment regimens (e.g. higher temperature or longer HT sessions) are necessary to elicit beneficial changes in skeletal muscle function in DMD.