<div> <div> <div> <p>Skeletal muscle occupies approximately 40 to 50 percent of body mass and is responsible for respiration, postural control, and locomotion and plays a pivotal role in regulating glucose, lipid, and protein metabolism. Acute muscle trauma and chronic disease conditions such as muscular dystrophies are associated with structural abnormalities, enhanced fatigability and impaired metabolism and consequently lead to exercise intolerance and poor quality of life. Despite the clinical importance and a number of studies on the treatment of muscle damage, few modalities have shown to elicit beneficial effects. Heat treatment has been used for a long time to treat soft tissue injuries in the field of physical therapy and sports medicine. However, the underlying mechanisms by which heat treatment accelerates muscle recovery following injury are not clear. </p> <p>The primary aim of my dissertation studies was to determine the impact of heat therapy on skeletal muscle structure and function in humans and animals. In Chapter 2, we report that a single session of local heat treatment promotes the expression of angiogenic and myogeneic mediators including vascular endothelial growth factor (VEGF) and angiopoietin 1(ANGPT1) in healthy human skeletal muscle. In Chapter 3, we report repeated exposure to heat therapy stimulates factors involved in muscle repair process and accelerates functional recovery from exercise-induced muscle damage. In Chapter 4, we show that 8 weeks of local heat therapy improves muscle strength of knee extensor and increases skeletal muscle capillarization in type II muscle fibers. In Chapter 5, we describe the effects of heat therapy in a mouse model of ischemia induced-muscle damage. Animals that were exposed to heat therapy at 39°C had improved maximal absolute force and relative muscle mass in the soleus muscle. These observations reveal that the beneficial effects of heat therapy are muscle fiber type specific and dependent on the treatment temperature. In Chapter 6, we review and summarize the outcomes described in Chapters 2-5 and provide a general conclusion as well the clinical implications of our findings. </p> </div> </div> </div>

Heat therapy may be an alternative or adjunct intervention to exercise training for improving cardiovascular function and health. However, its prescription must be refined in order to overcome the feasibility and tolerability issues associated with current whole-body heating modes. There is substantial evidence to support the beneficial effects of high doses (e.g., frequency, duration, and intensity) of heating typically achieved using whole-body modes, but there is limited knowledge on whether lower doses of heating administered through local hot water immersion of the limbs can still have an impact on vascular function. All studies were conducted in heathy young men and women. In the first study, we found that regardless of whether local heating was applied to the lower limbs up to the ankles or knees, upper limb endothelial function and lower limb arterial stiffness improved acutely. In the second study, we proceeded to prescribe ankle-level heating in a chronic intervention and compared its effects to that of moderate-intensity cycling exercise training. We observed no changes in endothelial function, but decreases in central arterial stiffness and increases in cardiorespiratory fitness in those who performed heat therapy and exercise training combined with heat therapy. In the third study, we evaluated the ability of acute vascular function responses to predict chronic vascular function responses with heating and exercise interventions, and found significant positive associations between the acute and chronic responses for absolute and relative brachial artery flow-mediated dilation and femoral-foot pulse wave velocity. These findings suggest that, in healthy young men and women, local heating through ankle-level hot water immersion can improve indices of cardiovascular function both acutely and chronically, alone or combined with exercise training. Further, acute responses may be used to determine an individual’s chronic responsiveness to a heat therapy and/or exercise training intervention. More research in larger, more diverse samples and with a longer duration of therapy and/or training should be conducted to determine if the results are replicable. / Dissertation / Doctor of Philosophy (PhD) / Regular participation in whole-body heat therapy can extend health and life span, but it is used infrequently because of a lack of feasibility from a cost, accessibility, and tolerability standpoint. This thesis explored whether local heat therapy in young healthy men and women would be effective for improving blood vessel health defined as endothelial function and arterial stiffness, both of which are linked to the risk of developing many chronic diseases. Furthermore, the effects of local heat therapy were compared to that of exercise training. We found that there were beneficial short- and long-term effects of lower limb hot water immersion that manifested in different areas of the body. Local heat therapy improved upper limb endothelial function and lower limb arterial stiffness immediately after a session, whereas with repeated exposure, it may have improved central arterial stiffness and cardiorespiratory fitness. Exercise training only had beneficial effects on the blood vessels when combined with heat therapy. Finally, short-term vascular responses can predict long-term vascular responses to both heat therapy and/or exercise training. Overall, our findings suggest that there may be some utility for local heat therapy to promote healthy blood vessels, but more work must be done to replicate our findings and explore its effects on other populations.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that increases a woman’s risk of developing cardiovascular disease and diabetes. Women with PCOS have extremely high rates of obesity, insulin resistance, cardiovascular morbidity and mortality. Obese women with PCOS also tend to have elevated sympathetic nerve activity and systemic markers of inflammation, which likely contribute to cardiometabolic risk and PCOS pathogenesis. While few medication or lifestyle intervention options for women with PCOS target elevated sympathetic nerve activity, inflammation, and insulin resistance, passive heat exposure shows promise as a novel intervention for improving cardiovascular and metabolic health in this population. Therefore, the purpose of this study was to examine changes in inflammation, cardiovascular, autonomic, and metabolic health in obese women with PCOS following a 30-session, 8-10 week chronic passive heat intervention (termed ‘heat therapy’). Eighteen obese women with PCOS (Age: 27±1y, BMI 41.3±1.1 kg·m2) were matched for age and body mass index (BMI), then divided into heat therapy (HT) or time control (CON). At the beginning (Pre), middle (Mid), and end (Post) of 8-10 weeks, subjects participated in study days to assess vascular, autonomic, and metabolic function, and additionally underwent a subcutaneous fat biopsy in Pre and Post. HT subjects took part in 30 one-hour hot tub sessions over 8-10 weeks (3-4 per week) in 40.5˚C water, while CON subjects completed all other testing but were not exposed to heat. No change in BMI was observed over the study in HT or CON; however; HT subjects exhibited dramatically improved vascular and metabolic function, as well as reduced sympathetic nerve activity and circulating inflammatory markers. In fat biopsies, insulin signaling was improved in HT subjects, while CON subjects remained stable over time. These findings show promise for HT as a treatment option for obese women with PCOS to improve cardiovascular and metabolic risk profiles. This dissertation includes previously published co-authored material.

<p>Lower extremity peripheral artery disease (PAD) is an increasingly prevalent manifestation of atherosclerosis that substantially limits mobility and increases mortality. Few options currently exists for practical conservative treatment of individuals with PAD. We have previously demonstrated that lower limb heat therapy (HT) can improve leg blood flow and reduce systolic blood pressure in patient with lower extremity PAD. Using three unique clinical trials, we sought to test the hypothesis that repeated exposure to HT would improve walking tolerance and vascular function in patients with lower extremity PAD. In these trials, we have sought to examine the clinical efficacy of HT, the physiological mechanisms which may underpin changes in walking endurance in this population, and also the practicality of employing HT in a home-based setting. The primary finding from these trials was that daily application of leg HT improved walking endurance in patients with lower-extremity PAD. Furthermore, the treatment adherence rate was excellent (<96%) and was not associated with severe adverse events. The changes in walking tolerance were consistently not associated with positive changes in vascular function, suggesting an alternative mechanism should be examined in future studies. </p>

Recent evidence suggests that heat, a major byproduct of exercise, may be the mediator for many vascular adaptations that come from exercise. Thus, heat therapy that increases muscle temperature in a comparable way to exercise may be an advantageous alternative for enhancing cardiovascular health in individuals where treatment with exercise is either not possible or undesired. PURPOSE: Compare the effects of exercise and heat training on resistance artery function at rest and during exercise. METHODS: Thirty-five (18 female) healthy, untrained subjects completed a 6-week training program utilizing either high intensity knee extension (KE) exercise (40 min), localized heat therapy (pulsed shortwave diathermy; 120 min), or a sham heat therapy protocol (120 min). We randomly selected 8 subjects from each group to have a temperature probe inserted into their vastus lateralis muscle during one of their training sessions to evaluate the effect of the interventions on muscle temperature. We assessed resistance artery function at rest with the passive leg movement technique (PLM) prior to and after completion of the training protocols. We assessed peak exercise blood flow (KE peak flow) and peak power output (KE peak power) during the KE graded exercise test and prior to and after completion of the training protocols. RESULTS: Peak muscle treatment temperature was significantly different between all groups with those assigned to the diathermy heat training exhibiting a higher peak temperature (~40.80°C) than those in the exercise (~37.75°C, P < 0.001) and sham training groups (~36.10°C, P < 0.001). KE peak flow during PLM increased to the same extent (P = 0.625) in both the exercise (~10.5% increase, P = 0.009) and heating groups (~8.5% increase, P = 0.044); but tended to decrease in the sham group (P = 0.087). KE peak flow increased in the exercise group (~19%, P = 0.005), but did not change in the heat group (P = 0.523) and decreased in the sham group (~7%, P = 0.020). Peak vascular conductance during KE significantly increased by ~25% in the exercise (P = 0.030) and heat (P = 0.012) groups. KE peak power increased in the exercise group by ~27% (P = 0.001) but did not significantly change in the heat (P = 0.175) and sham groups (P = 0.111). The change in vascular function, assessed via PLM, showed a correlation with both ∆KE peak flow (R = 0.55, P = 0.01) and ∆KE peak power (R = 0.56, P = .010). Likewise, ∆KE peak flow showed a strong association with ∆KE peak power (R = 0.64, P < 0.001). CONCLUSION: Localized diathermy heat treatment increased resistance artery function at rest and during exercise to a similar extent as single-leg KE exercise training but did not yield significant improvements in performance. Thus, heat training mimics some but not all of the benefits associated with exercise and may be used to replace exercise treatment to some extent.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The present study aimed to assess the heat generated by a therapeutic ultrasound (TUS) in a metal bone plate and adjacent structures after fixation to the femur of canine cadavers. Ten pairs of hindlimbs were used, and they were equally distributed between groups that were subjected to 1- and 3-MHz frequencies, with each frequency testing 1- and 2-W/cm² intensities. The right hindlimb was defined as the control group (absence of the metal plate), and the left hindlimb was the test group (presence of the metal plate). Therefore, the control groups (CG) were denominated CGI, using TUS with 1-MHz frequency and 1-W/cm² intensity; CGII, using 1-MHz frequency and 2-W/cm² intensity; CGIII, using 3-MHz frequency and 1-W/cm² intensity; and CGIV, using 3-MHz frequency and 2-W/cm² intensity. For each control group, its respective test group (TG) was denominated TGI, TGII, TGIII and TGIV, respectively. The TUS was applied to the lateral aspect of the thigh using the continuous mode and a 3.5-cm² transducer in a 6.25-cm² area for 2 minutes. Sensors were coupled to digital thermometers that measured the temperature in different sites before (t0) and after (t1) of the TUS application. The temperatures in t1 were higher in all tested groups. The intramuscular temperature was significantly higher (P < 0.05) in the groups used to test the 3-MHz frequency in the presence of the metal plate. The therapeutic ultrasound in the continuous mode using frequencies of 1 and 3 MHz and intensities of 1 and 2 W/cm2 for 2 minutes caused heating of the metal plate and adjacent structures after fixation to the femur of canine cadavers. / O objetivo deste estudo foi avaliar o aquecimento gerado pelo ultrassom terapêutico (UST) na placa óssea metálica e estruturas adjacentes após a fixação no fêmur de cadáveres caninos. Foram utilizados dez pares de membros pélvicos, distribuídos igualmente entre os grupos que utilizaram as frequências de 1 e 3 MHz. Cada frequência testou as intensidades de 1 e 2 W/cm², sendo que o membro pélvico direito foi definido grupo controle (ausência da placa óssea metálica) e o membro pélvico esquerdo o grupo teste (presença da placa óssea metálica). Portanto, os grupos controles foram denominados GCI, com UST na frequência de 1 MHz e intensidade de 1 W/cm², GCII com 1 MHz e 2 W/cm², GCIII com frequência de 3 MHz e intensidade de 1 W/cm² e GCIV com 3 MHz e 2 W/cm². Para cada grupo controle, seu respectivo grupo teste foi denominado GTI, GTII, GTIII e GTIV. O UST foi aplicado na face lateral da coxa utilizando o modo contínuo, transdutor de 3,5 cm² em uma área de 6,25 cm², durante dois minutos. Foram utilizados sensores acoplados a termômetros digitais que mediram a temperatura em diferentes locais antes (t0) e após (t1) a aplicação do UST. Pode-se verificar que as temperaturas em t1 foram maiores em todos os grupos testados. Os grupos que testaram a frequência de 3 MHz demonstraram que a temperatura intramuscular foi significativamente maior (P<0,05) na presença da placa óssea metálica. O ultrassom terapêutico no modo contínuo de 1 e 3 MHz e intensidades de 1 e 2 W/cm2 durante dois minutos promove o aquecimento da placa óssea metálica e estruturas adjacentes após a fixação no fêmur de cadáveres caninos.

M.Tech. / Purpose: This randomised, controlled, comparative pilot study was undertaken in order to investigate the effectiveness of the chiropractic manipulation alone, the chiropractic manipulation followed by heat therapy or the chiropractic manipulation followed by cryotherapy in the treatment of cervical facet syndrome. It was hypothesised that all three treatment protocols would be effective, but that applying chiropractic manipulation followed by heat therapy would be the most effective protocol in the treatment of cervical facet syndrome. Method: Forty-five participants were recruited by means of advertisements posted around the University of Johannesburg Doornfontein campus and surrounding businesses. Only those participants who conformed to the inclusion criteria were accepted to form a part of the study. The forty-five participants were randomly placed into three groups of fifteen each. Procedure: Group 1 received chiropractic manipulation only as their treatment protocol. Group 2 received chiropractic manipulation followed by heat therapy as their treatment protocol and group 3 received chiropractic manipulation followed by cryotherapy as their treatment protocol. Each participant received six treatments over a two week period and attended a follow-up consultation in the third week. The follow-up consultation was used to assess the lasting effects of the treatment protocol. Results: The objective data in the form of cervical range of motion was obtained by means of the Cervical Range of Motion instrument. The subjective data was collected by means of the Vernon-Mior Neck Pain and Disability Index and the Numerical Pain Rating Scale. At the end of the trial, statistical analysis was performed to determine whether one treatment protocol was more effective compared to the other treatment protocols. The results indicated that group 2 (Chiropractic manipulation followed by heat therapy) proved to be the most effective treatment protocol. Although the other treatment protocol as well as the control group showed good objective results. Subjective results showed that although all three groups showed statistically significant results, group 2 showed the best results. Thus it is noted that in order to achieve a potentially lasting increase in range of motion and a decrease in pain and disability, the treatment protocol used for group 2 should be the treatment of choice. Conclusion: Trends indicate the most effective treatment protocol in the treatment of cervical facet syndrome is when chiropractic manipulation is followed by heat therapy. The advantage of this combination is that each treatment modality is used to its full potential, thereby providing the patient with the best results in terms of lasting benefits.

Physical activity results in various types of stress in skeletal muscle including energetic, oxidative, and heat stress. Acute exposure to stress impairs skeletal muscle mitochondrial function. In contrast, chronic intermittent exposure to mild stress through exercise training results in increased mitochondrial content and respiratory capacity. While oxidative and energetic stress have received much attention regarding their long-term effect on skeletal muscle mitochondria, heat stress is not well understood. The purpose of this work was to investigate the effects of localized heat therapy on human skeletal muscle mitochondria, and to compare these effects to those of high-intensity interval exercise training. To accomplish this purpose, 35 subjects were assigned to receive 6 weeks of sham therapy, heat therapy, or exercise training; all localized to the quadriceps muscles of the right leg. Two-hour sessions of short-wave diathermy were used for the heat therapy, and identical sessions were used for sham therapy, but the diathermy units were not activated. Forty-minute sessions of single-leg extension, high-intensity interval training were used for the exercise intervention. All interventions took place three times per week. Muscle biopsies were performed at baseline, and after three and six weeks of intervention. Muscle fiber bundles were isolated and permeabilized for measurement of oxygen consumption via high-resolution respirometry. The primary finding of this work was that heat therapy improves mitochondrial respiratory capacity by 24.8 ± 6.2% compared to a 27.9 ± 8.7% improvement following exercise training. Both heat and exercise significantly increased mitochondrial respiration compared to baseline measures (p<0.05). Fatty acid oxidation and citrate synthase activity were also increased following exercise training by 29.5 ± 6.8% and 19.0 ± 7.4%, respectively (p<0.05). However, contrary to our hypothesis, heat therapy did not increase fatty acid oxidation or citrate synthase activity. Neither heat nor exercise training increased mitochondrial respiratory protein content. Overall these results suggest that heat therapy significantly improves mitochondrial function, but not to the same degree as exercise training.

<p>Oxygen (O2) plays a crucial role in the energy metabolism of complex multicellular life on earth. Due to the small and finite energy stores in the body, fine-tuned changes within the body are required to meet metabolic demand during skeletal muscle contractions, such as during exercise and activities of daily living. The skeletal muscle microcirculation is one of the last steps in the O2 transport pathway from the lungs to muscle cells and represents the largest surface area for O2 and substrate exchange. When skeletal muscle O2 uptake increases during contractions to meet metabolic demand, there must be an increase in muscle O2 delivery. To achieve these elevations in O2 delivery, vessel (arteriole) diameter in the microcirculation is increased, known as vasodilation. This process in the skeletal muscle microcirculation is regulated by several factors, such as neurohumoral, mechanical, endothelial, paracrine, and metabolic influences, which are imperative in properly regulating O2 delivery at rest and during muscular contractions. Two vasodilatory pathways of interest in this dissertation are the cyclooxygenase (COX) and nitric oxide (NO) vasodilatory pathways.</p> <p>The primary aim of my dissertation studies was to determine the mechanisms that modulate skeletal muscle oxygenation in health and to define the impact of a potentially effective intervention, whole-body chronic heat therapy (HT), to treat heart failure with preserved ejection fraction (HFpEF). In Chapter 2, we report that acute selective COX-2 inhibition had no effect on resting or exercising skeletal muscle microvascular oxygenation, pulmonary oxygen uptake, or exercise tolerance in healthy young humans. In Chapter 3, we report that NO, via phosphodiesterase type 5 inhibition, regulates myocyte O2 transport at rest and during recovery from muscle contractions in healthy young rats. In Chapter 4, we show that whole-body chronic HT promotes central and peripheral adaptations, which impact positively exercise tolerance in a pre-clinical rat model of HFpEF. Specifically, whole-body chronic HT had beneficial influences on exercise tolerance, skeletal muscle oxygenation from rest to contractions (driven, at least in part, by enhanced NO bioavailability), body composition, and cardiac function. Chapter 5 is a summary of the results and limitations of the projects presented in Chapters 2-4, with a brief discussion of potential future research directions. </p>