Waon Therapy Improves Peripheral Arterial Disease

To the Editor:We developed a form of thermal therapy, namely “Waon therapy” (soothing warm therapy) (1), which differs from the traditional sauna, and demonstrated that the repeated use of a dry sauna at 60°C improves hemodynamics and ameliorates symptoms and vascular function in patients with chronic heart failure (2,3). Nitric oxide (NO), constitutively produced by endothelial nitric oxide synthase (eNOS), is a mediator of angiogenesis. Recently, we reported that repeated Waon therapy increases eNOS protein expression, blood flow, and capillary density in a mouse model of hind limb ischemia (4). Furthermore, Waon therapy does not increase blood flow and capillary density in eNOS-deficient mice, and we conclude that eNOS is a critical regulator of angiogenesis by Waon therapy.

Peripheral arterial disease (PAD) is a major cause of acute and chronic illness, associated with decrements in functional capacity and quality of life. We conducted this study to evaluate the beneficial effect of repeated Waon therapy using infrared-ray dry sauna on patients with PAD.

Patients were qualified for Waon therapy if they had chronic limb ischemia, including claudication, rest pain, and/or nonhealing ischemic ulcers present for a minimum of 4 weeks without evidence of improvement in spite of conventional therapies and were not candidates for surgical or nonsurgical revascularization. Requisite hemodynamic deficits included a resting ankle-brachial pressure index (ABI) <0.9 in the affected limb on 2 consecutive examinations performed at least 1 week apart. We enrolled 20 patients with PAD, including 15 patients with bilateral limb ischemia and 5 patients with unilateral limb ischemia.

The patients were placed in a far infrared-ray dry sauna, in which the temperature was evenly maintained at 60°C for 15 min, and then were kept on a bed outside the sauna for additional 30 min with sufficient warmth provided by blankets (2). They were weighed before and after Waon therapy, and oral hydration with water was used to compensate for weight loss. This Waon therapy was performed once a day for 5 days per week for a period of 10 weeks. Data were compared using paired ttests.

All patients enrolled in the trial completed the study without any adverse events. The demographic and clinical data of patients treated with 10-week Waon therapy are summarized in Table 1.Therapeutic benefit was demonstrated by regression of rest pain in all patients. Ischemic ulcers healed in all of the 7 limbs, resulting in successful limb salvage.

Leg pain was scored by a visual analog scale, using a marked 10-cm line extending from “no pain: 0” to “severe pain: 10.” The pain score significantly decreased after 10 weeks of Waon therapy (Fig. 1A).Exercise performance, evaluated by the 6-min walking distance, improved in all 18 patients after 10 weeks of Waon therapy (Fig. 1B). We measured the ABI in 31 limbs, and the mean ABI significantly increased after Waon therapy (Fig. 1C). Serial assessment of leg blood flow was performed with laser Doppler imaging. It showed that blood flow increased after 10 weeks (Fig. 1D). Digital subtraction angiography was performed to evaluate new collateral vessel formation in 20 legs (13 patients), which showed a dramatic increase in the visible collateral vessels in 12 ischemic legs after 10 weeks of Waon therapy.

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Figure 1

Improvement in Pain, Walking, ABI, and Blood Flow After 10 Weeks of Waon Therapy

(A)Pain score evaluated by a visual analog scale (10 = severe pain, 0 = no pain) (n = 20); (B)6-min walking distance (n = 18); (C)ankle-brachial pressure index (ABI) (n = 31); and (D)laser Doppler perfusion imaging (n = 28). *p < 0.01.

In summary, we have shown that repeated Waon therapy is safe for patients with severe PAD and potentially effective as evidenced by a substantial decrease in the pain score, increases in ABI and blood flow assessed by laser Doppler perfusion imaging, and by formation of new collateral vessels on angiography. In addition, ischemic ulcers present in 7 limbs healed or improved markedly. Given the poor prognosis of patients with chronic critical limb ischemia in whom the possibility of spontaneous improvement is remote, the outcome in this study is encouraging.

We reported that angiogenesis was induced via eNOS using Waon therapy in mice with hind limb ischemia (4). Nitric oxide is a mediator of angiogenesis and plays a key role in angiogenesis induced by Waon therapy. Repeated Waon therapy increases cardiac output, shear stress of the vessel wall, and ultimately eNOS expression.

Aicher et al. (5) reported that the impaired neovascularization in mice lacking eNOS is related to a defect in progenitor cell mobilization, and eNOS is essential for mobilization of stem and progenitor cells. We believe that our Waon therapy increases the number of circulating endothelial progenitor cells via partially NO-dependent. This may contribute to angiogenesis in patients with PAD, who are characterized by a reduced systemic NO bioactivity.

Exercise also increases circulating endothelial progenitor cells, and supervised exercise training is recommended as an initial treatment modality for patients with intermittent claudication. The advantage of Waon therapy compared with exercise therapy for PAD is that we can successfully perform Waon therapy in patients who cannot exercise. Combinations of Waon therapy and exercise training might be useful for patients with PAD. Cellular and molecular therapeutic modalities for PAD have shown early efficacy. Therefore, we should analyze the synergistic effect of Waon therapy and gene transfer or therapeutic stem cell therapy.

We recently described one of the impressive patients (Patient #13 in Table 1) (6). His large skin ulcer healed completely after 15 weeks of Waon therapy, and limb amputation was avoided. In addition, 10 of 20 patients in this study were followed at our outpatient clinic and they continued Waon therapy at least twice per week. In the follow-up period ranging from 6 months to 3 years, none of them showed the worsening symptoms of PAD. Therefore, to maintain the effect of Waon therapy, we believe that treatment should be continued at least twice per week after discharge.

The limitation of this study is the lack of a control group. In the absence of a control group, the treatment effect cannot be estimated, confounding standard care variables are not defined, and enrollment bias could lead to comparable rates of clinical improvement. Randomized and controlled trials with larger numbers of patients with PAD will help to determine the efficacy of Waon therapy.

In conclusion, we demonstrated that Waon therapy improved symptoms, status, and blood flow in patients with PAD. Our Waon therapy method may therefore be a novel innovative therapy for patients with PAD.

• American College of Cardiology Foundation