My Research on Balneology, Sauna, Exercise and Rehabilitation Medicine / 日本温泉気候物理医学会雑誌

  My research started in 1973 at Kagoshima University Hospital Kirishima Branch founded at 1937. The hospital was reorganized as the Department of Rehabilitation Medicine and Kirishima Rehabilitation Center in 1988.   I established a new pharmacological method to measure integrated cardiovascular autonomic nervous functions, and essential hypertension was classified into two types, Type I with low sympathetic, low renin, Na-retention type and Type II with high sympathetic, high rennin, non-Na-retention type.   By bathing at 41°C for 10 min, an increase in HR and CO and decrease in TPRi was shown. Using autonomic blockers, tachycardia was shown to be derived by vagal inhibition and vasodilation by a non-autonomic mechanism. Scarlet coloring of venous blood due to increased pO2 and decreased pCO2 highly suggested improved tissue oxygenation as the basic bathing effects.   Tachycardia during exercise was derived firstly by increased sinus automaticity, and secondly vagal inhibition and sympathetic activation. Athletic bradycardia was induced firstly by decreased sinus automaticity, and secondly by vagal activation and sympathetic suppression.   Hemodynamic studies of Ibusuki sandbath showed a remarkable increase in CO and decrease in TPRi, and an increase in RAP and PAP due to heavy sand. Increased venous pO2 and decreased pCO2 and lactate-pyruvate level indicate highly accelelated tissue oxygenation and clearance of wasted material by increased peripheral circulation.   Although ICG clearance rate was reduced, increased acetoaminophen absorption indicated an increased intestinal blood flow. Increased RPF and unchanged GFR suggested suppressed intra-glomerular pressure from bathing. Urodynamic study after bathing, showed reduced intravesical pressure and increased bladder volume indicating the effects of bathing on pollakiuria in winter due to the relaxation of detrusor muscle.   Against the usual concept that bathing is harmful for CHF, we showed bathing at 40°C for 10 min was a very useful tool as a new vasodilation therapy for CHF. Sauna bathing at 60°C for 15 min was more convenient and Dr. Tei named it Waon therapy. He achieved remarkable improvements in NYHA class symptoms and circulatory parameters in severe CHF, i.e., CO, EF, intra cardiac pressure and BNP. Waon therapy was also shown to be very useful in peripheral arterial disease, post-operative paretic ileus and fibromyalgia.

My Research on Balneology, Sauna, Exercise and Rehabilitation Medicine / 日本温泉気候物理医学会雑誌

  My research started in 1973 at Kagoshima University Hospital Kirishima Branch founded at 1937. The hospital was reorganized as the Department of Rehabilitation Medicine and Kirishima Rehabilitation Center in 1988.<BR>  I established a new pharmacological method to measure integrated cardiovascular autonomic nervous functions, and essential hypertension was classified into two types, Type I with low sympathetic, low renin, Na-retention type and Type II with high sympathetic, high rennin, non-Na-retention type.<BR>  By bathing at 41°C for 10 min, an increase in HR and CO and decrease in TPRi was shown. Using autonomic blockers, tachycardia was shown to be derived by vagal inhibition and vasodilation by a non-autonomicmechanism. Scarlet coloring of venous blood due to increased pO₂ and decreased pCO₂ highly suggested improved tissue oxygenation as the basic bathing effects.<BR>  Tachycardia during exercise was derived firstly by increased sinus automaticity, and secondly vagal inhibition and sympathetic activation. Athletic bradycardia was induced firstly by decreased sinus automaticity, and secondly by vagal activation and sympathetic suppression.<BR>  Hemodynamic studies of Ibusuki sandbath showed a remarkable increase in CO and decrease in TPRi, and an increase in RAP and PAP due to heavy sand. Increased venous pO₂ and decreased pCO₂ and lactate-pyruvate level indicate highly accelelated tissue oxygenation and clearance of wasted material by increased peripheral circulation.<BR>  Although ICG clearance rate was reduced, increased acetoaminophen absorption indicated an increased intestinal blood flow. Increased RPF and unchanged GFR suggested suppressed intra-glomerular pressure from bathing. Urodynamic study after bathing, showed reduced intravesical pressure and increased bladder volume indicating the effects of bathing on pollakiuria in winter due to the relaxation of detrusor muscle.<BR>  Against the usual concept that bathing is harmful for CHF, we showed bathing at 40°C for 10 min was a very useful tool as a new vasodilation therapy for CHF. Sauna bathing at 60°C for 15 min was more convenient and Dr. Tei named it Waon therapy. He achieved remarkable improvements in NYHA class symptoms and circulatory parameters in severe CHF, i.e., CO, EF, intra cardiac pressure and BNP. Waon therapy was also shown to be very useful in peripheral arterial disease, post-operative paretic ileus and fibromyalgia.

Waon Therapy is Effective as the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome / 日本温泉気候物理医学会雑誌

Background: Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue. We examined the applicability of Waon therapy as a new method of fatigue treatment in patients with ME/CFS. Methods: Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Canadian clinical case definition of ME/CFS participated in this study. Patients received 30 sessions of modified Waon therapy, infrared-ray dry sauna maintained at an even temperature of 40°C or 45°C for 15 minutes twice a day for 3 weeks in a hospital, or once a day for five weeks at an outpatient clinic. Their functional health and well-being scores were determined using SF-36 and compared with those of six ME/CFS patients who did not undergo Waon therapy. Results: Seven of nine Waon therapy patients experienced a significant improvement in physical and mental condition, and the effect continued throughout the observation period. Waon therapy brought improvements in the scores of: Role physical (p<0.05); Bodily pain (p<0.05); General health perceptions (p<0.05); and Role emotional (p<0.05) of SF-36 in those who responded well (good responders) to the therapy. In two patients who responded poorly (poor responders) to Waon therapy, and in the non-Waon therapy patients, no significant improvement in the scores was observed. Conclusions: Waon therapy is effective for the treatment of ME/CFS.

Waon Therapy is Effective as the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome / 日本温泉気候物理医学会雑誌

<b>Background</b>: Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue. We examined the applicability of Waon therapy as a new method of fatigue treatment in patients with ME/CFS.<BR><b>Methods</b>: Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Canadian clinical case definition of ME/CFS participated in this study. Patients received 30 sessions of modified Waon therapy, infrared-ray dry sauna maintained at an even temperature of 40°C or 45°C for 15 minutes twice a day for 3 weeks in a hospital, or once a day for five weeks at an outpatient clinic. Their functional health and well-being scores were determined using SF-36 and compared with those of six ME/CFS patients who did not undergo Waon therapy.<BR><b>Results</b>: Seven of nine Waon therapy patients experienced a significant improvement in physical and mental condition, and the effect continued throughout the observation period. Waon therapy brought improvements in the scores of: Role physical (p<0.05); Bodily pain (p<0.05); General health perceptions (p<0.05); and Role emotional (p<0.05) of SF-36 in those who responded well (good responders) to the therapy. In two patients who responded poorly (poor responders) to Waon therapy, and in the non-Waon therapy patients, no significant improvement in the scores was observed.<BR><b>Conclusions</b>: Waon therapy is effective for the treatment of ME/CFS.

02-2 Preventive effect of thermal therapy on heart failure due to pressure overload / 日本温泉気候物理医学会雑誌

Introduction: Long-term cardiac hypertrophy causes heart failure. One of the mechanisms of this transition from hypertrophy to heart failure is collapse of hypoxic response and angiogenesis. Heat shock protein 27 (HSP27) was found to act as an anti-apoptotic protein and its phosphorylation is responsible for the protection of cells against heat stress. HSP27 has been reported to regulate p53 expression, which contributes to down-regulate angiogenic factors through hypoxia inducible factor-1α(HIF-1α). We have reported that thermal therapy, namely Waon therapy, improves cardiac and vascular function in patients with chronic heart failure. However, the effect of this therapy on cardiac hypertrophy due to pressure overload is unknown. The purpose of this study is to investigate the effects and mechanisms of thermal therapy (Waon therapy) on the transition from cardiac hypertrophy to heart failure after pressure overload. Methods: Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6 mice. At 2 weeks after TAC, all mice were examined by echocardiography and showed left ventricular hypertrophy. Then, mice were randomly divided into thermal therapy or untreated group. Thermal therapy group received thermal therapy using an experimental far infrared ray dry sauna, which elevates the core temperature by 1 degree Celsius for 30 minutes, daily for 4 weeks. Sham operated mice were used as control. At 6 weeks after TAC, we measured body weight, heart rate and blood pressure before sacrifice, and eviscerated heart and leg muscle. Western blot analysis of p53, phosphorylated HSP27, HIF-1α and vascular endothelial growth factor (VEGF) was performed using extracted protein form heart. Results: At 6 weeks after TAC, body weight, heart rate and blood pressure did not differ in three groups. Echocardiography showed that left ventricular fractional shortening of thermal therapy group was significantly larger than that of untreated group (Sham vs. Untreated vs. Thermal; 50.0±1.7 vs. 36.7±1.3 vs. 46.2±0.5, P<0.01, n=6 each). Heart weight/tibia length ratio of thermal therapy group was significantly smaller than that of untreated group (6.7±0.1 vs. 9.7±0.5 vs. 7.9±0.2, P<0.01, n=9 each). Western blot showed that thermal therapy increased phosphorylation of HSP27 and reduced p53. Thermal therapy also increased HIF-1α and VEGF at 6 weeks after TAC. Capillary/myofiber ratio was larger in thermal therapy group than that in untreated group (1.71±0.05 vs. 2.04±0.04 vs. 2.41±0.10, P<0.01, n=4 each). Conclusion: Thermal therapy, namely Waon therapy, prevented the transition from cardiac hypertrophy to heart failure induced by pressure overload in mice. As the mechanism, thermal therapy amplified the phosphorylation of HSP27 and inhibited p53, increased HIF-1α and VEGF, and then increased angiogenesis.

S1-5 The effects of Waon therapy for patients with chronic pain and fibromyalgia / 日本温泉気候物理医学会雑誌

Objectives: Many patients with chronic pain and fibromyalgia (FM) consult health care clinics continually, and move from hospital to hospital without gaining pain relief. In some patients, prolonged refractory pain affects their daily life and social function despite various treatments. The purpose of this study was to clarify the effects of Waon therapy in patients with chronic pain and FM. Patients and Methods: Study A: 46 patients with chronic pain were assigned to Waon therapy group (n = 22) or non-Waon therapy group (n = 24). All patients were admitted to our hospital for 5 weeks. In non-Waon therapy group, cognitive behavior therapy (CBT), rehabilitation, and exercise therapy were performed during hospitalization. Waon therapy was started 2 weeks after admission in addition to CBT, rehabilitation, and exercise therapy. And the therapy was performed for 4 weeks. Pain was evaluated by the visual analog scale (VAS). Pain behavior was assessed based on the 11 items and the number per day was counted. Anger score was evaluated using the mentral complaints in the Cornell Medical Index. The degree of satisfaction with treatment was evaluated at discharge. Study B: 12 patients who fulfilled the FM criteria of the American College of Rheumatology. All patients received 20 sessions of Waon Therapy at our outpatients clinic. The VAS pain scale and the Fibromyalgia Impact Questionnaire (FIQ), Profile of Mood State (POMS) were evaluated before and after 10 and 20 sessions of Waon Therapy. Results: Study A: The differences in number of pain behavior and anger scores before and after treatment were significantly larger in Waon therapy group than those in non-Waon therapy group. The treatment was rated as ‘satisfactory’ or ‘very satisfactory’ by 55% in non-Waon-therapy group and 82% in Waon Therapy group. Study B: The VAS pain scores and FIQ scores were improved after the 10 and 20 sessions of Waon therapy. In the POMS, depression and anger, anxiety, confusion scales were sigificantly decresed and vigor score was elevated. Conclusion: Waon therapy may be a promising method for treatment of chronic pain and fibromyalgia.

S1-4 Waon therapy for myalgic encephalomyelitis/chronic fatigue syndrome / 日本温泉気候物理医学会雑誌

Objective: Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue lasting for at least 6 months. There are many controlled trials and case-control treatment studies that utilized immunological substances, pharmacological products, nutritional supplements, physical therapies, and cognitive behavioral therapy. Because of the unclear etiology, diagnostic uncertainty, and the resultant heterologeneity of the ME/CFS population, there are no firmly established treatment recommendation for ME/CFS. Recently Tei et al reported 2 CFS cases in whom thermal therapy improved the subjective symptoms. Thermal therapy has been reported to increase stroke volume and cardiac output in patients and improve the quality of life, sleep quality, and general well-being of these subjects. Thermal therapy using far-infrared ray dry sauna may be a promising method for the treatment of ME/CFS. We examined the applicability of Waon therapy (soothing warmth therapy) as a new treatment for patients with ME/CFS. Methods: Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Ministry of Health, Labor and Welfare of Japan and Canadian clinical case definition of ME/CFS participated in this study. The mean illness duration was 3.1±1.8 years (range, 1-6). The mean performance state was 6.9±0.9. The patients were placed in the sitting position in a infrared-ray dry sauna maintained at an even temperature of 45°C for 15 minutes, and then transferred to a room maintained at 26-27°C where they were covered with a warm blanket from the neck down to keep them warm for 30 minutes. They received thermal therapy twice a day for 3 weeks in hospital or once a day at the outpatient clinic for 5weeks. Their functional health and well-being scores were determined using SF-36 before treatment, after 30 treatments and during follow-up (mean follow-up period, 27.9±10.5 months; range 7-40). Results: Seven patients experienced a significant improvement in physical and mental condition by Waon therapy, and the effect continued throughout the observation period. In two patients, no improvement of symptoms was observed. Waon therapy brought the improvement in the score of Physical functioning(p<0.05), Role physical(RP)(p<0.05), Bodily pain(p<0.001), General health perceptions(p<0.03) and Role emotional(RE)(p<0.005) of FS-36 in good responders. However, the therapy did not bring any improvement in the score of Vitality, Social functioning and Mental health.   In poor responders, no improvement was observed in the score of FS-36. Mean duration of illness in poor responders was longer than in good responders (4.5±0.7ys:2.7±1.9ys, p<0.09). The performance state at the admission was almost same between poor responders and good responders (7±0:6.9±1.1). Conclusion: Waon therapy is effective for the treatment of ME/CFS. Although the present study included only 10 patients, the effects observed in our patients were dramatic. Further clinical studies in larger ME/CFS patient populations are required to confirm the effects of this method of treatment.

S1-1 Waon therapy for cardiovascular disease / 日本温泉気候物理医学会雑誌

  In 1989, we developed a form of thermal therapy for heart failure. In 2007, I changed the name to Waon therapy: “Wa” means soothing, and “On” means warmth, hence Waon infers soothing warmth that comfortably refreshes the mind and body.   “Waon therapy” is defined as “therapy in which the entire body is warmed in an evenly maintained in a far infrared dry sauna at a temperature of 60°C for 15 min, and then rest supine on a bed outside the sauna where they are covered with blankets for an additional 30 min, with fluids corresponding to perspiration being supplied at the end.”   Waon therapy has several characteristic features, that is, safe and no toxicity, gentle and cost effective. It is just a holistic medical care and gives a global optimization to the patients with refractory diseases.   There are various clinical applications of “Waon therapy and the effects are often dramatic. In particular, a drastic recovery is often seen in severe congestive heart failure (CHF) as well as peripheral artery disease (PAD) with intractable ulcer, chronic fatigue syndrome, fibromyalgia syndrome and salivary secretion failure caused by Sjögren’s syndrome etc. In this presentation, I would like to focus the effects and mechanisms of Waon therapy on refractory CHF and PAD.   We demonstrated that Waon therapy improved the hemodynamics, cardiac function, ventricular arrhythmias, vascular endothelial function, neurohumoral factors, sympathetic and para-sympathetic nervous system function, and also found that 2 - 4 weeks of Waon therapy (once a day, 5 days a week) significantly improved clinical symptoms, and deceased BNP and cardiac size in patients with CHF. Waon therapy improved the prognosis of CHF patients as well as CHF models of hamster and mouse. It has also been demonstrated that the molecular mechanism by which Waon therapy improves vascular flow and expression of endothelial nitric oxide synthase (eNOS) and capillary density.   Moreover, repeated Waon therapy is effective for patients with severe PAD, as evidenced by substantial decrease in pain scores, increases in both ankle-brachial pressure index and blood flow assessed by laser Doppler perfusion imaging, and by formation of new collateral vessels on angiography. Waon therapy often heals ischemic ulcers markedly. Waon therapy upregulates heat shock protein 90 (Hsp90) and leads to angiogenesis through the akt-eNOs pathway in mouse hindlimb ischemia.   In conclusion, Waon therapy is an innovative and highly promising strategy for cardiovascular diseases, especially treating refractory CHF and PAD.

S1-1Waon therapy for cardiovascular disease / 日本温泉気候物理医学会雑誌

  In 1989, we developed a form of thermal therapy for heart failure. In 2007, I changed the name to Waon therapy: “Wa” means soothing, and “On” means warmth, hence Waon infers soothing warmth that comfortably refreshes the mind and body.<BR>  “Waon therapy” is defined as “therapy in which the entire body is warmed in an evenly maintained in a far infrared dry sauna at a temperature of 60°C for 15 min, and then rest supine on a bed outside the sauna where they are covered with blankets for an additional 30 min, with fluids corresponding to perspiration being supplied at the end.” <BR>  Waon therapy has several characteristic features, that is, safe and no toxicity, gentle and cost effective. It is just a holistic medical care and gives a global optimization to the patients with refractory diseases.<BR>  There are various clinical applications of “Waon therapy and the effects are often dramatic. In particular, a drastic recovery is often seen in severe congestive heart failure (CHF) as well as peripheral artery disease (PAD) with intractable ulcer, chronic fatigue syndrome, fibromyalgia syndrome and salivary secretion failure caused by Sjögren’s syndrome etc. In this presentation, I would like to focus the effects and mechanisms of Waon therapy on refractory CHF and PAD. <BR>  We demonstrated that Waon therapy improved the hemodynamics, cardiac function, ventricular arrhythmias, vascular endothelial function, neurohumoral factors, sympathetic and para-sympathetic nervous system function, and also found that 2 - 4 weeks of Waon therapy (once a day, 5 days a week) significantly improved clinical symptoms, and deceased BNP and cardiac size in patients with CHF. Waon therapy improved the prognosis of CHF patients as well as CHF models of hamster and mouse. It has also been demonstrated that the molecular mechanism by which Waon therapy improves vascular flow and expression of endothelial nitric oxide synthase (eNOS) and capillary density. <BR>  Moreover, repeated Waon therapy is effective for patients with severe PAD, as evidenced by substantial decrease in pain scores, increases in both ankle-brachial pressure index and blood flow assessed by laser Doppler perfusion imaging, and by formation of new collateral vessels on angiography. Waon therapy often heals ischemic ulcers markedly. Waon therapy upregulates heat shock protein 90 (Hsp90) and leads to angiogenesis through the akt-eNOs pathway in mouse hindlimb ischemia. <BR>  In conclusion, Waon therapy is an innovative and highly promising strategy for cardiovascular diseases, especially treating refractory CHF and PAD.

S1-5The effects of Waon therapy for patients with chronic pain and fibromyalgia / 日本温泉気候物理医学会雑誌

<b>Objectives: </b>Many patients with chronic pain and fibromyalgia (FM) consult health care clinics continually, and move from hospital to hospital without gaining pain relief. In some patients, prolonged refractory pain affects their daily life and social function despite various treatments. The purpose of this study was to clarify the effects of Waon therapy in patients with chronic pain and FM.<BR><b>Patients and Methods: </b><BR><b>Study A:</b> 46 patients with chronic pain were assigned to Waon therapy group (n = 22) or non-Waon therapy group (n = 24). All patients were admitted to our hospital for 5 weeks. In non-Waon therapy group, cognitive behavior therapy (CBT), rehabilitation, and exercise therapy were performed during hospitalization. Waon therapy was started 2 weeks after admission in addition to CBT, rehabilitation, and exercise therapy. And the therapy was performed for 4 weeks. Pain was evaluated by the visual analog scale (VAS). Pain behavior was assessed based on the 11 items and the number per day was counted. Anger score was evaluated using the mentral complaints in the Cornell Medical Index. The degree of satisfaction with treatment was evaluated at discharge. <BR><b>Study B: </b>12 patients who fulfilled the FM criteria of the American College of Rheumatology. All patients received 20 sessions of Waon Therapy at our outpatients clinic. The VAS pain scale and the Fibromyalgia Impact Questionnaire (FIQ), Profile of Mood State (POMS) were evaluated before and after 10 and 20 sessions of Waon Therapy. <BR><b>Results: </b><BR><b>Study A: </b>The differences in number of pain behavior and anger scores before and after treatment were significantly larger in Waon therapy group than those in non-Waon therapy group. The treatment was rated as ‘satisfactory’ or ‘very satisfactory’ by 55% in non-Waon-therapy group and 82% in Waon Therapy group. <BR><b>Study B: </b>The VAS pain scores and FIQ scores were improved after the 10 and 20 sessions of Waon therapy. In the POMS, depression and anger, anxiety, confusion scales were sigificantly decresed and vigor score was elevated. <BR><b>Conclusion:</b> Waon therapy may be a promising method for treatment of chronic pain and fibromyalgia.

S1-4Waon therapy for myalgic encephalomyelitis/chronic fatigue syndrome / 日本温泉気候物理医学会雑誌

<b>Objective: </b>Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue lasting for at least 6 months. There are many controlled trials and case-control treatment studies that utilized immunological substances, pharmacological products, nutritional supplements, physical therapies, and cognitive behavioral therapy. Because of the unclear etiology, diagnostic uncertainty, and the resultant heterologeneity of the ME/CFS population, there are no firmly established treatment recommendation for ME/CFS. Recently Tei et al reported 2 CFS cases in whom thermal therapy improved the subjective symptoms. Thermal therapy has been reported to increase stroke volume and cardiac output in patients and improve the quality of life, sleep quality, and general well-being of these subjects. Thermal therapy using far-infrared ray dry sauna may be a promising method for the treatment of ME/CFS. We examined the applicability of Waon therapy (soothing warmth therapy) as a new treatment for patients with ME/CFS.<BR><b>Methods: </b>Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Ministry of Health, Labor and Welfare of Japan and Canadian clinical case definition of ME/CFS participated in this study. The mean illness duration was 3.1±1.8 years (range, 1-6). The mean performance state was 6.9±0.9. The patients were placed in the sitting position in a infrared-ray dry sauna maintained at an even temperature of 45°C for 15 minutes, and then transferred to a room maintained at 26-27°C where they were covered with a warm blanket from the neck down to keep them warm for 30 minutes. They received thermal therapy twice a day for 3 weeks in hospital or once a day at the outpatient clinic for 5weeks. Their functional health and well-being scores were determined using SF-36 before treatment, after 30 treatments and during follow-up (mean follow-up period, 27.9±10.5 months; range 7-40).<BR><b>Results:</b> Seven patients experienced a significant improvement in physical and mental condition by Waon therapy, and the effect continued throughout the observation period.<BR>In two patients, no improvement of symptoms was observed. Waon therapy brought the improvement in the score of Physical functioning(p<0.05), Role physical(RP)(p<0.05), Bodily pain(p<0.001), General health perceptions(p<0.03) and Role emotional(RE)(p<0.005) of FS-36 in good responders. However, the therapy did not bring any improvement in the score of Vitality, Social functioning and Mental health. <BR>  In poor responders, no improvement was observed in the score of FS-36. Mean duration of illness in poor responders was longer than in good responders (4.5±0.7ys:2.7±1.9ys, p<0.09). The performance state at the admission was almost same between poor responders and good responders (7±0:6.9±1.1).<BR><b>Conclusion:</b> Waon therapy is effective for the treatment of ME/CFS. Although the present study included only 10 patients, the effects observed in our patients were dramatic. Further clinical studies in larger ME/CFS patient populations are required to confirm the effects of this method of treatment.

02-2Preventive effect of thermal therapy on heart failure due to pressure overload / 日本温泉気候物理医学会雑誌

<b>Introduction:</b> Long-term cardiac hypertrophy causes heart failure. One of the mechanisms of this transition from hypertrophy to heart failure is collapse of hypoxic response and angiogenesis. Heat shock protein 27 (HSP27) was found to act as an anti-apoptotic protein and its phosphorylation is responsible for the protection of cells against heat stress. HSP27 has been reported to regulate p53 expression, which contributes to down-regulate angiogenic factors through hypoxia inducible factor-1α(HIF-1α). We have reported that thermal therapy, namely Waon therapy, improves cardiac and vascular function in patients with chronic heart failure. However, the effect of this therapy on cardiac hypertrophy due to pressure overload is unknown. The purpose of this study is to investigate the effects and mechanisms of thermal therapy (Waon therapy) on the transition from cardiac hypertrophy to heart failure after pressure overload.<BR><b>Methods:</b> Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6 mice. At 2 weeks after TAC, all mice were examined by echocardiography and showed left ventricular hypertrophy. Then, mice were randomly divided into thermal therapy or untreated group. Thermal therapy group received thermal therapy using an experimental far infrared ray dry sauna, which elevates the core temperature by 1 degree Celsius for 30 minutes, daily for 4 weeks. Sham operated mice were used as control. At 6 weeks after TAC, we measured body weight, heart rate and blood pressure before sacrifice, and eviscerated heart and leg muscle. Western blot analysis of p53, phosphorylated HSP27, HIF-1α and vascular endothelial growth factor (VEGF) was performed using extracted protein form heart.<BR><b>Results: </b>At 6 weeks after TAC, body weight, heart rate and blood pressure did not differ in three groups. Echocardiography showed that left ventricular fractional shortening of thermal therapy group was significantly larger than that of untreated group (Sham vs. Untreated vs. Thermal; 50.0±1.7 vs. 36.7±1.3 vs. 46.2±0.5, P<0.01, n=6 each). Heart weight/tibia length ratio of thermal therapy group was significantly smaller than that of untreated group (6.7±0.1 vs. 9.7±0.5 vs. 7.9±0.2, P<0.01, n=9 each). Western blot showed that thermal therapy increased phosphorylation of HSP27 and reduced p53. Thermal therapy also increased HIF-1α and VEGF at 6 weeks after TAC. Capillary/myofiber ratio was larger in thermal therapy group than that in untreated group (1.71±0.05 vs. 2.04±0.04 vs. 2.41±0.10, P<0.01, n=4 each).<BR><b>Conclusion:</b> Thermal therapy, namely Waon therapy, prevented the transition from cardiac hypertrophy to heart failure induced by pressure overload in mice. As the mechanism, thermal therapy amplified the phosphorylation of HSP27 and inhibited p53, increased HIF-1α and VEGF, and then increased angiogenesis.

The Effect of Waon Therapy on Failed Myocardium and Ischemic Limb via Heat Shock Proteins / 日本温泉気候物理医学会雑誌

 Waon therapy uses a far infrared-ray dry sauna, which is evenly maintained at 60°C and differs from the traditional sauna. The patients were placed in a 60°C sauna system for 15 minutes, in which the deep-body temperature has increased by 1.0 to 1.2°C. Then, after leaving the sauna, they underwent bed rest with a blanket to keep them warm for an additional 30 minutes. All patients were weighed before and after the therapy, and they drank some water at the end of Waon therapy to compensate for weight lost due to perspiration and prevent the dehydration.  We have previously reported that Waon therapy improves the cardiac and vascular endothelial function in patients with chronic heart failure (CHF) and the limb ischemia and symptoms in patients with arteriosclerosis obliterans (ASO). As underlying molecular mechanisms, we demonstrated that Waon therapy upregulates nitric oxide (NO) and endothelial NO synthase (eNOS), which would improve vascular endothelial and cardiac function in TO-2 cardiomyopathic hamsters and augment ischemia-induced angiogenesis. In order to investigate the mechanism of Waon therapy, we examined the effect of Waon therapy on heat shock proteins (Hsp) in failed myocardium and ischemic limb. Hsp are stress response proteins that can be induced by stress signals, including thermal stimulation. Hsp function as chaperones to assist with protein folding in order to protect cells from protein denaturation or cell death under stress conditions.  In TO-2 cardiomyopathic hamsters, the cardiac expression of 4-hydroxy-2-nonenal (4HNE), a marker of oxidative stress, was decreased in the 4-week Waon therapy compared to untreated hamsters. Also, the cardiac expressions of Hsp 27, Hsp 32 and manganese superoxide dismutase (Mn-SOD), which reduce oxidative stress, were significantly upregulated by the 4-week Waon therapy compared to untreated hamsters. In addition, Waon therapy upregulated Hsp90, which contributes to the activation of the AkteNOSNO pathway, and induced angiogenesis in mice with hindlimb ischemia. However, Waon therapy did not increase the expression of Hsp70, Hsp60, Hsp32 and Hsp27 in the same model mice. The thermal stimulation with Waon therapy upregulated specific Hsp isoforms depending on different organs and diseases. The specific function of Hsp induced by Waon therapy is suggested to play an important role in improving cardiovascular diseases.

The Effect of Waon Therapy on Failed Myocardium and Ischemic Limb via Heat Shock Proteins / 日本温泉気候物理医学会雑誌

 Waon therapy uses a far infrared-ray dry sauna, which is evenly maintained at 60°C and differs from the traditional sauna. The patients were placed in a 60°C sauna system for 15 minutes, in which the deep-body temperature has increased by 1.0 to 1.2°C. Then, after leaving the sauna, they underwent bed rest with a blanket to keep them warm for an additional 30 minutes. All patients were weighed before and after the therapy, and they drank some water at the end of Waon therapy to compensate for weight lost due to perspiration and prevent the dehydration.<br> We have previously reported that Waon therapy improves the cardiac and vascular endothelial function in patients with chronic heart failure (CHF) and the limb ischemia and symptoms in patients with arteriosclerosis obliterans (ASO). As underlying molecular mechanisms, we demonstrated that Waon therapy upregulates nitric oxide (NO) and endothelial NO synthase (eNOS), which would improve vascular endothelial and cardiac function in TO-2 cardiomyopathic hamsters and augment ischemia-induced angiogenesis. In order to investigate the mechanism of Waon therapy, we examined the effect of Waon therapy on heat shock proteins (Hsp) in failed myocardium and ischemic limb. Hsp are stress response proteins that can be induced by stress signals, including thermal stimulation. Hsp function as chaperones to assist with protein folding in order to protect cells from protein denaturation or cell death under stress conditions.<br> In TO-2 cardiomyopathic hamsters, the cardiac expression of 4-hydroxy-2-nonenal (4HNE), a marker of oxidative stress, was decreased in the 4-week Waon therapy compared to untreated hamsters. Also, the cardiac expressions of Hsp 27, Hsp 32 and manganese superoxide dismutase (Mn-SOD), which reduce oxidative stress, were significantly upregulated by the 4-week Waon therapy compared to untreated hamsters. In addition, Waon therapy upregulated Hsp90, which contributes to the activation of the AkteNOSNO pathway, and induced angiogenesis in mice with hindlimb ischemia. However, Waon therapy did not increase the expression of Hsp70, Hsp60, Hsp32 and Hsp27 in the same model mice. The thermal stimulation with Waon therapy upregulated specific Hsp isoforms depending on different organs and diseases. The specific function of Hsp induced by Waon therapy is suggested to play an important role in improving cardiovascular diseases.

Preliminary Clinical Experience with Waon Therapy in Korea: Safety and Effect

BACKGROUND: Waon therapy has beneficial effects on chronic heart failure (CHF), peripheral arterial disease, and other various diseases. This was to assess the safety and effect of Waon therapy by echocardiography for the first time in Korea. METHODS: Ten patients with CHF were enrolled. The patients with a light gown were placed in a sitting-position in an evenly maintained 60degrees C dry sauna system for 15 minutes, and then after leaving the sauna, they underwent bed rest with a blanket to keep them warm for an additional 30 minutes. Waon therapy was performed once a day, 5 days a week. RESULTS: Four of the 5 patients who had been treated for more than 2 weeks as protocol noted improvement of heart failure (HF) symptoms and decrease in left ventricular (LV) volume. There were trends in improvement of LV ejection fraction and parameters of diastolic function after the therapy although statistical significance was lack. No one complained of worsening of HF symptoms. In each session, body weight (61.8+/-10.2 kg vs. 61.6+/-10.3 kg, p=0.008) and blood pressure (systolic, 119+/-28 vs. 111+/-27 mmHg, p=0.005; diastolic, 69+/-12 mmHg vs. 63+/-10 mmHg, p=0.005) were significantly decreased, oral temperature (35.9+/-0.4degrees C vs. 37.0+/-0.9degrees C, p=0.017) was increased by 1.0degrees C at the end of sauna bathing, but the heart rate (71+/-10/min vs. 72+/-8/min, p=0.8) was not changed. CONCLUSION: We have experienced Waon therapy which was safe and well tolerated and some beneficial effects for patients with CHF. Large scale randomized study is needed to apply Waon therapy as a promising therapy in Korean HF patients.