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The application of an orthostatic stress such as lower body negative pressure (LBNP) has been proposed to minimize the effects of weightlessness on the cardiovascular system and subsequently to reduce the cardiovascular deconditioning. The KAATSU training is a novel method to induce muscle strength and hypertrophy with blood pooling in capacitance vessels by restricting venous return. Here, we studied the hemodynamic, autonomic nervous and hormonal responses to the restriction of femoral blood flow by KAATSU in healthy male subjects, using the ultrasonography and impedance cardiography. The pressurization on both thighs induced pooling of blood into the legs with pressure-dependent reduction of femoral arterial blood flow. The application of 200 mmHg KAATSU significantly decreased left ventricular diastolic dimension (LVDd), cardiac output (CO) and diameter of inferior vena cava (IVC). Similarly, 200 mmHg KAATSU also decreased stroke volume (SV), which was almost equal to the value in standing. Heart rate (HR) and total peripheral resistance (TPR) increased in a similar manner to standing with slight change of mean blood pressure (mBP). High-frequency power (HF(RR)) decreased during both 200 mmHg KAATSU and standing, while low-frequency/high-frequency power (LF(RR)/HF(RR)) increased significantly. During KAATSU and standing, the concentration of noradrenaline (NA) and vasopressin (ADH) and plasma renin activity (PRA) increased. These results indicate that KAATSU in supine subjects reproduces the effects of standing on HR, SV, TPR, etc., thus stimulating an orthostatic stimulus. And, KAATSU training appears to be a useful method for potential countermeasure like LBNP against orthostatic intolerance after spaceflight.

High-intensity exercise shares similarities with acute phase responses of inflammatory diseases. We investigated the influences of acute exercise on inflammatory markers, plasma pentraxin3 (PTX3) and serum high-sensitive C-reactive protein (CRP) (hsCRP). Nine healthy male subjects (41 ± 3 years old) participated. Each subject performed three types of exercise; ergometer exercise at 70% workload of anaerobic threshold (AT) for 30 min (70% AT exercise), peak ergometer exercise (peak EX, 20 watt increase/min until fatigue) and resistance exercises of 70% 1 RM (70% RE) until exhaustion. We measured plasma PTX3, serum hsCRP, lactate, noradrenaline (NOR), white blood cells (WBC), interleukin-6 (IL-6) and myeloperoxidase (MPO), a marker of neutrophil degranulation. The effects of exercise on intracellular PTX3 and MPO in neutrophils were also investigated, by using flow cytometry analysis. Circulating PTX3 and hsCRP significantly increased immediately after 70% RE and peak EX, while they did not increase after 70% AT exercise. The exercise-induced fold increase in PTX3 and hsCRP relative to the resting level was positively correlated with the changes in WBC, NOR, lactate and MPO. The exercise-induced fold increase in IL-6 was positively correlated with that in NOR, but not with that in PTX3 and hsCRP. Neutrophils isolated immediately after 70% RE, but not 70% AT exercise, exhibited lower mean fluorescence for PTX3 and MPO than those from pre-exercise blood. These results provide the evidence that high-intensity exercises significantly increase circulatory PTX3 as well as hsCRP. The release from peripheral neutrophils is suggested to be involved in the exercise-induced plasma PTX3 increase.

The KAATSU training is a unique method of muscle training with restricting venous blood flow, which might be applied to prevent muscle atrophy during space flight, but the effects of KAATSU in microgravity remain unknown. We investigated the hemodynamic responses to KAATSU during actually simulated weightlessness (6° head-down tilt for 24 h, n  = 8), and compared those to KAATSU in the seated position before bed rest. KAATSU was applied to the proximal ends of both the thighs. In the seated position before bed rest, sequential incrementing of KAATSU cuff pressure and altering the level of blood flow restriction resulted in a decrease in stroke volume (SV) with an increase in heart rate (HR). KAATSU (150–200 mmHg) decreased SV comparable to standing. Following 24-h bed rest, body mass, blood volume (BV), plasma volume (PV), and diameter of the inferior vena cava (IVC) were significantly reduced. Norepinephrine (NOR), vasopressin (ADH), and plasma renin activity (PRA) tend to be reduced. A decrease in SV and CO induced by KAATSU during the simulated weightlessness was larger than that in the seated position before bed rest, and one of eight subjects developed presyncope due to hypotension during 100 mmHg KAATSU. High-frequency power (HF RR ) decreased during KAATSU and standing, while low-frequency/high-frequency power (LF RR /HF RR ) increased significantly. NOR, ADH and PRA also increased during KAATSU. These results indicate that KAATSU blood flow restriction reproduces the effects of standing on HR, SV, NOR, ADH, PRA, etc., thus stimulating a gravity-like stress during simulated weightlessness. However, syncope due to lower extremity blood pooling and subsequent reduction of venous return may be induced during KAATSU in microgravity as reported in cases of lower-body negative pressure.

Concurrent improvements in aerobic capacity and muscle hypertrophy in response to a single mode of training have not been reported. We examined the effects of low-intensity cycle exercise training with and without blood flow restriction (BFR) on muscle size and maximum oxygen uptake (VO2max). A group of 19 young men (mean age ± SD: 23.0 ± 1.7 years) were allocated randomly into either a BFR-training group (n=9, BFR-training) or a non-BFR control training group (n=10, CON-training), both of which trained 3 days/wk for 8 wk. Training intensity and duration were 40% of VO2max and 15 min for the BFR-training group and 40% of VO2max and 45 min for the CON-training group. MRI-measured thigh and quadriceps muscle cross-sectional area and muscle volume increased by 3.4-5.1% (P < 0.01) and isometric knee extension strength tended to increase by 7.7% (p < 0.10) in the BFR-training group. There was no change in muscle size (~0.6%) and strength (~1.4%) in the CON-training group. Significant improvements in VO2max (6.4%) and exercise time until exhaustion (15.4%) were observed in the BFR-training group (p < 0.05) but not in the CON-training group (-0.1 and 3. 9%, respectively). The results suggest that low-intensity, short-duration cycling exercise combined with BFR improves both muscle hypertrophy and aerobic capacity concurrently in young men. Key pointsConcurrent improvements in aerobic capacity and muscle hypertrophy in response to a single mode of training have not been reported.In the present study, low-intensity (40% of VO2max) cycle training with BFR can elicit concurrent improvement in muscle hypertrophy and aerobic capacity.

Concurrent improvements in aerobic capacity and muscle hypertrophy in response to a single mode of training have not been reported. We examined the effects of low-intensity cycle exercise training with and without blood flow restriction (BFR) on muscle size and maximum oxygen uptake ([VO.sub.2max]). A group of 19 young men (mean age ± SD: 23.0 ± 1.7 years) were allocated randomly into either a BFR-training group (n=9, BFR-training) or a non-BFR control training group (n=10, CON-training), both of which trained 3 days/wk for 8 wk. Training intensity and duration were 40% of [VO.sub.2max] and 15 min for the BFR-training group and 40% of [VO.sub.2max] and 45 min for the CON-training group. MRI-measured thigh and quadriceps muscle cross-sectional area and muscle volume increased by 3.4-5.1% (P < 0.01) and isometric knee extension strength tended to increase by 7.7% (p < 0.10) in the BFR-training group. There was no change in muscle size ( 0.6%) and strength ( 1.4%) in the CON-training group. Significant improvements in [VO.sub.2max] (6.4%) and exercise time until exhaustion (15.4%) were observed in the BFR-training group (p < 0.05) but not in the CON-training group (-0.1 and 3.9%, respectively). The results suggest that low-intensity, short-duration cycling exercise combined with BFR improves both muscle hypertrophy and aerobic capacity concurrently in young men.

Background. To control advanced cervical squamous cell carcinoma more effectively and more easily, we used neoadjuvant chemotherapy, with three drugs carboplatin, ifosfamide, and peplomycin (PIP), in a study performed from July 1990 to October 1994 in nine Institutions. Methods. Sixty-five patients with untreated, inoperable squamous cell carcinoma of the cervix were treated with carboplatin (300 mg/m^sup 2^ IV; low-dose PIP regimen, or 400 mg/m^sup 2^ IV; high-dose PIP regimen) on day 1, ifosfamide (1000 mg/m^sup 2^, IV) on days 1-3, and peplomycin (5 mg/body, IM) on days 1-6. The low-dose PIP was given between July 1990 and April 1992, and the high-dose PIP from May 1992 to October 1994. Results. Response rates for the low- and high-dose PIP regimens were 42.9% (12/28) and 59.5% (22/37), respectively. Measurable lesions were recognized in the cervix, pelvic lymph node (PeN), paraaortic lymph node (PAN), lung, and supraclavicular lymph node. Response rates in these individual lesions to our low- and high-dose PIP regimens were 35.7% (10/28) and 55.6% (20/36), respectively in the cervical lesion and more than 50% for both regimens in the PeN and PAN metastatic lesions, while the supraclavicular lymph node metastatic lesions responded poorly to both regimens. After low-dose PIP, surgery was performed in 2 patients (2/28; 7.1%), while after high-dose PIP, 12 patients (12/37; 32.4%) underwent surgery. The 3-year survival rate of patients with high-dose PIP was significantly higher than that of those with low-dose PIP (P < 0.01). Conclusions. Neoadjuvant chemotherapy with PIP appears feasible and effective. The link between dosage and treatment response and achievable surgery rate and survival rates suggests that results might be further optimized by considering patients' renal function, and utilizing the Calvert formula for dosing analysis.[PUBLICATION ABSTRACT]