Impact of heat therapy on skeletal muscle structure and function in a mouse model of peripheral arterial disease
Authors: Kim Kyoungrae , Reid Blake A. , Ro Bohyun , Hester Bryan C. , Casey Caitlin A. , Song Qifan , Roseguini Bruno T. 
Published: June 2021

IntroductionAlterations in skeletal muscle morphology and function, including increased connective tissue infiltration and reduced strength, contribute to exercise intolerance in patients with symptomatic peripheral arterial disease (PAD). We tested the hypothesis that repeated exposure to heat therapy (HT) would reverse skeletal muscle abnormalities in a mouse model of PAD.MethodsMale 42‐week‐old C57Bl/6 mice underwent bilateral ligation of the femoral artery to induce hindlimb ischemia. After two weeks of recovery, the animals were randomly assigned to receive HT or a control intervention. Heat therapy was applied by placing the animal in a flat bottom restrainer and immersing the lower half of the body in a glass container filled with water at 37°C (n=12), 39°C (n=12), or 41°C (n=12) for 30 min daily over 3 consecutive weeks. Animals assigned to the control group (n=12) were also restrained, but were placed in an empty container. Rectal temperature was measured before and during exposure to a single session of HT or the control intervention (n=2/group). Forty‐eight hours following the last treatment session, the animals were anesthetized and the soleus and extensor digitorium longus (EDL) muscles were harvested for the assessment of contractile function in vitro and histological determination of fiber morphology and collagen infiltration.ResultsRectal temperature increased rapidly during exposure to HT and reached a steady state within approximately 10 min (37ºC: 37.1±0.1°C, 39ºC: 38.7±0.2°C, 41ºC: 40.1±0.1°C), while in the control group rectal temperature remained at baseline levels throughout the session (34.9±1.1°C). Muscle weight relative to body weight was significantly higher in animals exposed to HT at 39ºC as compared to the control group in both the soleus (Control: 0.36±0.01 mg/g vs. 39HT: 0.41±0.01 mg/g, p=0.023) and EDL muscles (Control: 0.43±0.01 mg/g vs. 39HT: 0.48±0.01 mg/g, p=0.029). Maximal absolute force of the soleus tended to be higher in animals treated with HT at 37ºC (p=0.072) and at 39ºC (p=0.108) when compared to the control group (Control: 274.3±7.7 mN, 37ºC: 303.0±7.8 mN, 39 ºC: 301.1±13.5 mN). In the EDL muscle, collagen content was lower in the group treated with HT at 37ºC (Control: 5.1±1.3% vs. 37ºC: 2.9±0.8%, p=0.028). Similarly, there was a tendency for lower collagen infiltration in the soleus muscle in the group treated with HT at 39ºC when compared to the control group (Control: 5.7±0.8% vs. 39ºC: 4.6±1.4%, p=0.101). There were no differences between groups in specific muscle force, number of fibers with central nucleation and fiber‐cross sectional area in both the EDL and soleus muscles.ConclusionThese findings suggest that repeated exposure to HT at 37°C and 39°C, but not at 41°C, ameliorates skeletal muscle abnormalities in a mouse model of PAD.Support or Funding InformationFunding: Ralph W. and Grace M. Showalter Research Trust AwardThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.