Acute impact of a single session of thermotherapy on the expression of angiogenic regulators in human skeletal muscle

The decline of muscle capillarity, also known as microvascular rarefaction, is a common symptom and significant contributor to exercise intolerance in several chronic diseases such as peripheral artery disease, chronic heart failure and chronic obstructive pulmonary disease. Exercise is the most successful therapy to promote capillary growth (i.e. angiogenesis) in skeletal muscle. Unfortunately, a considerable fraction of patients with these chronic conditions cannot participate or fail to adhere to structured exercise programs. An urgent need remains for the development of novel, more accessible therapies to promote skeletal muscle angiogenesis. Thermotherapy (TT) has shown to increase exercise tolerance in these patients, and may do so in part by promoting skeletal muscle angiogenesis. However, the molecular mechanisms behind this effect remain unclear. Understanding these mechanisms, and the effect of TT on angiogenic regulators could further promote the use of this novel approach as a treatment for microvascular rarefaction. Forty-one young, healthy, adults were exposed to either an acute session of TT or a control session. TT treatment was applied using a water-circulating trouser connected to a water bath. During the TT session, water at 48°C was circulated through the garment for 90 min, while water at 33°C was used in the control condition. Biopsies from the vastus lateralis muscle taken at baseline, 30 minutes post treatment, and 120 minutes post treatment to determine the impact of TT on the mRNA levels of angiogenic regulators. When compared to the control group, individuals treated with TT had higher skeletal muscle expression of VEGF, ANG 2, MCP-1/CCL2, Fractalkine/CX3CL1, and PF4 30 minutes after the intervention. Conversely, FOXO-1 mRNA expression was lower in TT-treated individuals 120 min after the intervention. In conclusion, a single bout of TT promotes changes in the expression of key angiogenic regulators in human skeletal muscle

Thermotherapy reduces blood pressure and circulating endothelin-1 concentration and enhances leg blood flow in patients with symptomatic peripheral artery disease

Leg thermotherapy (TT) application reduces blood pressure (BP) and increases both limb blood flow and circulating levels of anti-inflammatory mediators in healthy, young humans and animals. The purpose of the present study was to determine the impact of TT application using a water-circulating garment on leg and systemic hemodynamics and on the concentrations of circulating cytokines and vasoactive mediators in patients with symptomatic peripheral artery disease (PAD). Sixteen patients with PAD and intermittent claudication (age: 63 ± 9 yr) completed three experimental sessions in a randomized order: TT, control intervention, and one exercise testing session. The garment was perfused with 48°C water for 90 min in the TT session and with 33°C water in the control intervention. A subset of 10 patients also underwent a protocol for the measurement of blood flow in the popliteal artery during 90 min of TT using phase-contrast MRI. Compared with the control intervention, TT promoted a significant reduction in systolic (∼11 mmHg) and diastolic (∼6 mmHg) BP (P < 0.05) that persisted for nearly 2 h after the end of the treatment. The serum concentration of endothelin-1 (ET-1) was significantly lower 30 min after exposure to TT (Control: 2.3 ± 0.1 vs. TT: 1.9 ± 0.09 pg/ml, P = 0.026). In addition, TT induced a marked increase in peak blood flow velocity (∼68%), average velocity (∼76%), and average blood flow (∼102%) in the popliteal artery (P < 0.01). These findings indicate that TT is a practical and effective strategy to reduce BP and circulating ET-1 concentration and enhance leg blood flow in patients with PAD