Introduction Short‐term exposure to heat stress has been shown to enhance muscle strength and elicit mitochondrial adaptations in human skeletal muscle. We recently documented that exposure to five sessions of heat therapy (HT) accelerates the recovery of fatigue resistance following exercise‐induced muscle damage in humans. However, the long‐term impact of repeated exposure to local heat stress on contractile function and skeletal muscle structure remains unknown. The purpose of the present study was to examine the effects of 8 weeks of daily treatment with local HT on muscle strength, fatigability, fiber size and mitochondrial content in humans. Methods Twelve healthy young adults (23.6±1.4 years, BMI 24.9±0.9 kg/m2) had one randomly selected thigh treated with daily HT for 8 consecutive weeks while the opposite thigh served as a control. A water‐circulating garment perfused with water at ~52ºC was used to apply HT for 90 min daily. Knee extensor strength (single peak torque during 3 repetition maximums at 180°/s and 60°/s) and fatigue resistance (total work during 40 repetition maximums at 180°/s) were assessed using isokinetic dynamometry before and after 4 and 8 weeks of treatment. Biopsies were obtained from the vastus lateralis muscle for the determination of myofiber cross‐sectional area and maximal citrate synthase activity. Results Treatment with HT elicited an increase in thigh skin temperature (39.8±0.1ºC), while skin temperature remained at baseline levels in the control thigh (32.4± 0.1ºC). A significant treatment effect was observed for the changes from baseline in peak isokinetic torque at 180º/s (p=0.04). On average, the changes in peak isokinetic torque from baseline for HT were ~2 fold higher than control at week 4 (Control: 4.1±3.7 Nm vs. HT: 9±4.6 Nm) and ~4 fold higher at week 8 (Control: 1.7±2.7 Nm vs. HT: 7.7±2.9 Nm). There were no differences between treatments for peak isokinetic torque at 60º/s, myofiber cross‐sectional area and citrate synthase activity. Conclusion These results indicate that daily exposure to HT for 8 weeks enhances muscle strength in humans. Local HT may be a practical therapeutic approach to improve muscle function in individuals with limited mobility and skeletal muscle weakness. Support or Funding Information Support: American College of Sports Medicine Research Endowment This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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.

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.