Abstract

Background : We developed a form of thermal therapy that differers from the traditional sauna. We reported that repeated thermal therapy upregulated eNOS protein and augmented ischemia-induced angiogenesis in a mouse model of hindlimb ishemia. Furthermore, we demonstrated that repeated thermal therapy improved limb ischemia in patients with peripheral artery disease (PAD). To investigate the underlying mechanism of thermal therapy for the treatment of PAD, we examined whether thermal therapy could mobilize blood-derived progenitor cells for local vascular regeneration. Method : We enrolled 6 patients with PAD and 4 patients with spinal canal stenosis (SCS) as a control. They were treated with a far infrared-ray dry sauna at 60 degrees centigrade for 15 minutes and then kept on bed rest with a blanket for 30 minutes, daily for 6 weeks. The leg pain was scored with a visual analogue scale (10: severest pain, 0: no pain). Ankle-brachial pressure index (ABI) and distance of 6-minute walking were measured before and 6 weeks after repeated thermal therapy. To detect the shift of circulating CD34+ progenitor cells in the periphery with higher sensitivity, we established the use of quantitative real-time polymerase chain reaction (PCR) for CD34 messenger RNA using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene as an internal control. Results : After 6 weeks of thermal therapy, the leg pain score, ABI, and distance of 6- minute walking were significantly improved in patients with PAD, while did not change in patients with SCS. Circulating CD34+ cell numbers were determined biweekly by quantitative real-time PCR before and after the initiation of repeated thermal therapy. In successfully treated patients with PAD, the number of cells increased 1.8-fold from 2.0 ± 1.5 (x10 −4 ) before thermal therapy to 3.6 ± 2.3 (x10 −4 ) after thermal therapy (p=0.018), while the number of cells in patients with SCS was 2.5 ± 0.6 (x10 −4 ) before thermal therapy and 2.5 ± 0.7 (x10 −4 ) after thermal therapy (no significant difference). Conclusion : Repeated thermal therapy mobilized circulating endothelial progenitor cells and improved limb ischemia in patients with PAD. This therapy is a novel, safe, and highly promising strategy for treating PAD.

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