The effect of sepsis and reactive oxygen species on skeletal muscle interstitial oxygen pressure during contractions.

OBJECTIVE: This study aims to examine the effect of sepsis on the dynamics of skeletal muscle partial oxygen pressure during muscle contractions as well as the effect of reactive oxygen species (ROS) scavenger (ascorbic acid, Asc). METHODS: Twenty-seven male Sprague-Dawley rats (2-3 months old) were randomly assigned to three groups; sham, cecal ligation and puncture (CLP), or CLP plus ascorbic acid treatment group (CLP + Asc). Electrical stimuli-induced muscle contractions and partial oxygen pressure measurements were performed at 3 h after CLP. The interstitial oxygen pressure (PO2 is) in the spinotrapezius muscle was measured by the phosphorescence quenching method. RESULTS: The PO2 is at rest was not different between the three groups. The PO2 is decreased from rest to contraction in all groups. Compared to the sham, the time to decrease PO2 is was significantly faster in CLP but not in CLP + Asc (p < .05). Compared to the sham, the PO2 is during muscle contractions was significantly lower in both CLP and CLP + Asc (p < .05, respectively). CONCLUSIONS: Our results suggest that CLP-induced sepsis accelerated the decay of PO2 is at the onset of muscle contractions and maintained a low level of PO2 is during muscle contractions.

Transcapillary PO2 Gradients in Contracting Muscles of Type I Diabetic Rats.

OBJECTIVE: This study aimed to clarify the effect of Type I diabetes (DIA) on transcapillary PO2 gradients, which are oxygen-driving factors between the blood and the interstitium, in the contracting muscle of rats. METHODS: Wistar male rats were divided into the diabetic (streptozocin i.p.) and sham groups. Microvascular and interstitial PO2 were measured in the extensor digitorum longus muscle during electrical stimulation-induced muscle contraction, using the phosphorescence quenching method. Transcapillary PO2 gradient, ΔPO2, was calculated as microvascular minus interstitial PO2. RESULTS: Resting microvascular PO2 was higher in the diabetic group than in the sham group (6.3 ± 1.7 vs. 4.7 ± 0.9 mmHg, p < 0.05) and remained for 180 s. Interstitial PO2 from rest to muscle contraction did not differ between the groups. The ΔPO2 was higher in the diabetic group than in the sham group at rest and during muscle contraction (4.03 ± 1.42 vs. 2.46 ± 0.90 mmHg at rest; 3.67 ± 1.51 vs. 2.22 ± 0.65 mmHg during muscle contraction, p < 0.05). Marked muscle atrophy was observed in the diabetic group. CONCLUSION: DIA increased microvascular and transcapillary PO2 gradients in the skeletal muscle. The enhanced PO2 gradients were maintained from rest to muscle contraction in diabetic muscle.

Leg fidgeting alleviates reduced oxygen extraction in the gastrocnemius muscle caused by prolonged sitting: a randomized crossover trial.

PURPOSE: Oxygen extraction in skeletal muscle is an important determinant of exercise tolerance. Prolonged sitting decreases oxygen extraction in the gastrocnemius muscle. However, the underlying mechanism remains unknown, and preventive measures are yet to be established. Therefore, we aimed to elucidate the mechanism by which prolonged sitting decreased muscle oxygen extraction and investigate preventive measures. METHODS: Ten healthy young males (age 21.2 ± 0.4 years; body mass index, 20.5 ± 1.3 kg/m2) were randomly assigned to each of the following conditions: 3-h supine (CON), 3-h sitting (SIT), and 3-h fidgeting of one lower leg during sitting (FID). Oxygen extraction from the gastrocnemius muscle was measured using near-infrared spectroscopy and the vascular occlusion test under each condition. The rate of change in total Hb + Mb (THb) was measured as an indicator of venous stasis and interstitial fluid accumulation in the lower leg. RESULTS: Muscle oxygen extraction was significantly lower at 180 min for SIT and FID than for CON (4384.2 ± 1426.8; 5281.5 ± 1823.7; 6517.4 ± 1390.8 a.u., respectively) and significantly higher for FID than for SIT (5281.5 ± 1823.7 vs. 4384.2 ± 1426.8 a.u., respectively). The rate of THb change was significantly higher at 180 min for SIT than for CON and FID (12.9 ± 15.1; -2.3 ± 5.7; 2.2 ± 11.6%, respectively). However, no significant difference was observed between CON and FID. CONCLUSION: We found that 3-h prolonged sitting reduced oxygen extraction in the gastrocnemius muscles due to reduced oxygen supply to capillaries and increased distance between capillaries and myocytes. However, leg fidgeting alleviated this effect in healthy young males. TRIAL REGISTRATION NUMBER: UMIN000050531 (March 8, 2023).

Effects of whole-body neuromuscular electrical stimulation device on hemodynamics, arrhythmia, and sublingual microcirculation.

Neuromuscular electrical stimulation has been used to treat cardiovascular diseases and other types of muscular dysfunction. A novel whole-body neuromuscular electrical stimulation (WB-NMES) wearable device may be beneficial when combined with voluntary exercises. This study aimed to investigate the safety and effects of the WB-NMES on hemodynamics, arrhythmia, and sublingual microcirculation. The study included 19 healthy Japanese volunteers, aged 22-33 years, who were not using any medication. Electrocardiogram (ECG), echocardiography, and blood sampling were conducted before a 20-min WB-NMES session and at 0 and 10 min after termination of WB-NMES. Their tolerable maximum intensity was recorded using numeric rating scale. Arrhythmia was not detected during neuromuscular electrical stimulation or during 10 min of recovery. Blood pressure, heart rate, left ventricular ejection fraction, and diastolic function remained unchanged; however, mild mitral regurgitation was transiently observed during WB-NMES in a single male participant. A decrease in blood glucose and an increase in blood lactate levels were observed, but no changes in blood fluidity, sublingual microcirculation, blood levels of noradrenaline, or oxidative stress were shown. WB-NMES is safe and effective for decreasing blood glucose and increasing blood lactate levels without changing the blood fluidity or microcirculation in healthy people.

Extended Sedentary Time Increases the Risk of All-Cause Death and New Cardiovascular Events in Patients With Diabetic Kidney Disease.

BACKGROUND: Sedentary behavior may be an independent risk factor for cardiovascular events. This study aimed to clarify the effects of extended sedentary time in patients with diabetic kidney disease (DKD) on the risk of all-cause death and new events.Methods and Results:A prospective cohort study was performed over 39 months. The study included 173 patients with DKD who completed the International Physical Activity Questionnaire (IPAQ) (101 men; mean age, 71±11 years); 37 patients (21.4%) were diagnosed with cardiovascular disease (CVD). New events were defined as all-cause death, cerebral stroke, or CVD requiring hospitalization or commencing hemodialysis (HD). Data were analyzed using a multivariate Cox proportional hazard regression model with variables, including sedentary time. There were 34 cases of new events during the observation period, including 4 cases of stroke, 20 cases of CVD, 4 cases of HD implementation, and 6 cases of death. Hazard ratio (HR) calculations for the new event onset group identified sedentary time as a significant independent variable. The independent variable that was identified as a significant predictor of new events was the sedentary time (60 min/day; HR: 1.23, 95% CI: 1.05-1.45, P=0.012). CONCLUSIONS: Extended sedentary time increased the risk of new cardiovascular or renal events and/or all-cause death in patients with DKD.

Acute Effects of Skeletal Muscle Electrical Stimulation on Central and Lower Extremity Hemodynamics.

INTRODUCTION: Belt electrode-skeletal muscle electrical stimulation (B-SES) is a treatment prescribed for individuals with difficulty performing exercise therapy that improves muscle strength, exercise tolerance, and glucose metabolism. However, the effects of B-SES on the hemodynamics of the central and lower extremity conduit arteries have not been studied. Therefore, this study compared the acute effects of B-SES on the central and lower extremity conduit arteries in healthy young males. METHODS: This randomized crossover study included nine healthy young males (mean age: 21.0±1.1 years). Participants were assigned to the following experimental conditions, with a washout period of one week: condition 1 included 20 min of electrical stimulation of the lower extremity at the participant's sensation threshold intensity (Sham, n=9) and condition 2 included 20 min of electrical stimulation of the lower extremity at the maximum intensity the participant can tolerate (B-SES, n=9). The heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), and total peripheral vascular resistance (TPR) were measured as central hemodynamics. The hemodynamics of the lower extremity conduit arteries were measured and calculated for the shallow femoral artery (SFA), including vessel diameter, mean blood flow velocity (MBFV), shear rate (SR), and mean blood flow (MBF) rate. These indices were measured before stimulation (Pre), 10 min after the start of stimulation (Stimulating), and immediately after the end of stimulation (Post). These indices were compared using a repeated two-way analysis of variance. RESULTS: In B-SES, HR (Pre: 63.2±8.6; Stimulating: 73.7±6.9; Post: 70.0±4.2 bpm, p<0.01), CO (Pre: 5.1±1.0; Stimulating: 6.5±1.5, p<0.01; Post: 6.3±1.2 L/min, p=0.02), and MAP (Pre: 104.0±11.5; Stimulating: 116.4±10.8, p<0.01; Post: 109.6±9.7 mmHg, p=0.02) increased significantly. In addition, B-SES significantly increased MBFV (Pre: 19.2±4.0; Stimulating: 50.5±14.9; Post: 30.1±4.0 cm/s, p<0.01), SR (Pre: 118.9±28.8; Stimulating: 302.7±91. 2, p<0.01; Post: 182.1±70.1/s, p=0.02), and MBF (Pre: 382.0±61.5; Stimulating: 1009.6±321.4; Post: 626.8±176.6 mL/min, p<0.01). However, there were no significant changes in SV and TPR. CONCLUSIONS: The findings of this study indicate that B-SES in healthy young males increases CO without increasing SV or TPR and improves the MBFV and SR in the SFA.

Prolonged Sitting Induces Elevated Blood Pressure in Healthy Young Men: A Randomized Crossover Trial.

Introduction Prolonged sitting-induced blood pooling in the lower legs can increase blood pressure through increased sympathetic nerve activity and peripheral vascular resistance, an aspect that has been understudied as a primary outcome. This study compared the effects of prolonged sitting with those of prolonged supination on blood pressure in healthy young men. Methods This randomized crossover study included 16 healthy young men (mean age: 21.6 ± 0.7 years) who were randomly assigned to a three-hour supine (CON) or three-hour sitting (SIT) condition, followed by a washout period of at least one week. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), low-frequency/high-frequency (LF/HF) ratio derived from heart rate variability, and leg circumference were measured at 60, 120, and 180 minutes from baseline. These indices were compared by two-way (time × conditions) analysis of variance (ANOVA). Results In the SIT condition, DBP, MAP, HR, LF/HF ratio, and leg circumference increased significantly over time (P < 0.05) and were significantly higher than those in the CON condition (P < 0.05). However, SBP showed no significant change over time and between conditions. Conclusions The findings indicate the involvement of sympathetic nerve activity and increased peripheral vascular resistance induced by fluid retention in the lower legs with increased DBP and MAP in healthy young men.

Relationship Among Falls, Fear of Falling, and Physical Activity Level in Patients on Hemodialysis.

OBJECTIVE: Patients on hemodialysis are highly susceptible to falls and fractures. Amplified apprehension regarding the fear of falling (FOF) constitutes a risk factor that restricts physical activity and escalates the probability of falls among the elderly population. This study aimed to elucidate the association between falls and FOF and physical activity in patients on hemodialysis. METHODS: A prospective cohort study was conducted across 9 centers. FOF was assessed using the Falls Efficacy Scale-International (FES-I). Physical activity was assessed using the Japanese version of the International Physical Activity Questionnaire short form. Subsequently, falls were monitored over a duration of 1 year. Logistic regression analysis was performed to evaluate the relationship between falls and FOF and physical activity. In addition, in the receiver operating characteristic analysis, the cutoff value of FES-I that predicts falls was determined using the Youden Index. A restricted cubic spline curve was utilized to analyze the nonlinear association between falls and the FES-I. RESULTS: A total of 253 patients on hemodialysis (70.0 [59.0-77.0] years old; 105 female [41.5%]) were included in the analysis. During the 1-year observation period, 90 (35.6%) patients experienced accidental falls. The median FES-I score was 36.0 (24.0-47.0) points, and patients with higher FES-I scores had more falls. Following adjusted logistic regression analysis, FES-I exhibited an independent association with falls (OR = 1.04; 95% CI = 1.01-1.06), but physical activity was not. The area under the receiver operating characteristic curve was 0.70 (95% CI = 0.64-0.77), and the FES-I threshold value for distinguishing fallers from non-fallers was determined as 37.5 points (sensitivity 65.6%, specificity 35.0%). A nonlinear relationship between falls and FES-I was observed. CONCLUSION: FOF was associated with the incidence of falls in patients on hemodialysis. IMPACT: The evaluation and implementation of interventions targeting the FOF may mitigate the risk of falls.

Differences Between Brachial-Ankle Pulse Wave Velocity and Lower Leg Circumference Ratio in Patients With and Without Type 2 Diabetes Mellitus.

Background Vascular endothelial dysfunction in type 2 diabetes mellitus (T2DM) patients causes atherosclerosis and microvascular damage. This study investigated the relationship between leg circumference and arterial stiffness in patients with T2DM compared to non-T2DM individuals. Methods Data from two studies were combined to form T2DM (T2DM group) and non-T2DM (N group) cohorts. The variables included age, sex, systolic blood pressure (SBP), brachial-ankle pulse wave velocity (ba-PWV), ankle-brachial index, height, weight, maximum leg circumference, lower leg circumference ratio, duration of T2DM, Achilles tendon reflex disorder, and the hemoglobin A1c level. Multiple regression analysis was performed with ba-PWV as the dependent variable and the interaction term between leg circumference ratio and T2DM as the independent variable. The control variables included leg circumference ratio, T2DM, SBP, Achilles tendon reflex disorder, age, and sex. IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, NY, USA) was used for the statistical analysis, with the significance level set to p < 0.05. Results The interaction term between the lower leg circumference ratio and T2DM (ß = -0.17, 95% CI: -46.11 to -10.92; p < 0.01) was significantly associated with ba-PWV (AdjR² = 0.51, variance inflation factor <4.12). Simple slope analysis indicated that a decreased lower leg circumference ratio was significantly associated with an increased ba-PWV (ß = -0.20, p < 0.05) in the T2DM group. No significant relationship was found in the N group (ß = -0.03, p = 0.69). Conclusion A significant interaction was found between the lower leg circumference ratio and T2DM presence, indicating an association between ba-PWV and the leg circumference ratio specific to patients with T2DM. This result suggests that the leg circumference ratio can be substituted for the ba-PWV to evaluate arterial stiffness in T2DM.

Skeletal Muscle Quality Assessment in Patients With Cardiac Disease Associated With Type 2 Diabetes Mellitus: A Pilot Study.

Background Type 2 diabetes mellitus (T2DM) is associated with changes in skeletal muscle quantity and quality, such as increased ectopic fat. Cardiac rehabilitation (CR) aims to improve the exercise capacity and muscle strength. This study aimed to determine the relationship between qualitative changes in the skeletal muscles and exercise function in patients with and without diabetes mellitus. Methods The study included patients with cardiovascular diseases who entered CR. Of 72 CR patients (68.1±9.0 years) who underwent a cardiopulmonary exercise test and skeletal muscle assessment at discharge, 15 patients with T2DM and 15 without DM were selected using propensity score matching by age and gender. Results No significant differences in the skeletal muscle echo intensity (EI) (T2DM: 58.4, Non-DM: 53.4, p=0.32), skeletal muscle index (T2DM: 7.5 kg/m2, Non-DM: 7.2 kg/m2, p=0.36), or the weight-bearing index (WBI)(T2DM: 0.44, Non-DM: 0.50, p=0.35) existed between the two groups. The phase angle (PhA) (T2DM: 3.67°, Non-DM: 4.49°, p<0.05) and peak oxygen uptake (T2DM: 12.3 mL/kg/min, Non-DM: 14.8 mL/kg/min, p<0.05) were significantly lower in the T2DM group. PhA values showed a significant correlation with the WBI, a parameter of lower limb muscle strength (r=0.50, p<0.05). Conclusion The coexistence of cardiovascular disease and T2DM resulted in a decrease in the PhA, indicating a qualitative decrease in skeletal muscle mass. The PhA is also associated with lower limb muscle strength.

Long-Term Tailor-Made Exercise Intervention Reduces the Risk of Developing Cardiovascular Diseases and All-Cause Mortality in Patients with Diabetic Kidney Disease.

This study aimed to determine the effect of long-term exercise on the risk of developing cardiovascular diseases (CVD) and all-cause mortality in patients with diabetic kidney disease (DKD). A single-center, prospective intervention study using propensity score matching was performed over 24 months. The intervention group (n = 67) received six months of individual exercise instruction from a physical therapist, who performed aerobic and muscle-strengthening exercises under unsupervised conditions. New events were defined as the composite endpoint of stroke or CVD requiring hospitalization, initiation of hemodialysis or peritoneal dialysis, or all-cause mortality. The cumulative survival rate without new events at 24 months was significantly higher in the intervention group (0.881, p = 0.016) than in the control group (n = 67, 0.715). Two-way analysis of variance revealed a significant effect of the group factor on high density lipoprotein-cholesterol (HDL-C) which was higher in the intervention group than in the control group (p = 0.004); eGFRcr showed a significant effect of the time factor, which was lower at 24 months than before intervention (p = 0.043). No interactions were observed for all items. In conclusion, aerobic exercises combined with upper and lower limb muscle strengthening for six months reduce the risk of developing CVD and all-cause mortality in patients with DKD.

Decreased Physical and Daily Living Activities in Patients with Peripheral Arterial Disease on Hemodialysis.

Decreased physical activity and activities of daily living (ADL) in patients on hemodialysis (HD) are associated with a poor prognosis. Additionally, comorbid peripheral arterial disease is associated with further deterioration. We conducted a cross-sectional study of ADL difficulty and life-space assessment (LSA) in three groups of patients on hemodialysis according to their ankle-brachial index (ABI) values. The 164 patients were divided into ABI Low (ABI < 0.9), Normal (0.9 ≤ ABI < 1.3), and High (1.3 ≤ ABI) groups, and compared using analysis of covariance with LSA and ADL difficulty adjusted for age. The Kihon checklist (KCL) was used to assess the presence of frailty. The LSA was lower in the Low group than in the High group (F = 3.192, p = 0.044). Similarly, the ADL difficulty was significantly lower in the Low group than in the Normal group (F = 3.659, p = 0.028). In the Low group, the proportion of patients with frailty was 47.1% and KCL physical was significantly lower, indicating that patients on HD with a lower ABI had a higher prevalence of frailty and lower LSA and ADL difficulty. In conclusion, patients on HD with decreased ABI values most likely exhibit decline in physical activity and ADL due to frailty and claudication.

Neuromuscular Electrical Stimulation during Hemodialysis Suppresses Postprandial Hyperglycemia in Patients with End-Stage Diabetic Kidney Disease: A Crossover Controlled Trial.

Hemodialysis patients with diabetic kidney disease (DKD) experience blood glucose fluctuations owing to insulin removal. We evaluated the effects of single and long-term application of neuromuscular electrical stimulation (NMES) during hemodialysis on glycemic control. This trial was conducted in two stages: Stage 1, following a crossover design and 4 week washout period, eleven outpatients with DKD either underwent a single bout of NMES for 30 min (NMES period) or rested (control period) after receiving nutritional support during hemodialysis; Stage 2, following a crossover design and 4 week washout period, each participant received the intervention for 12 weeks. NMES was administered for 30 min at the maximum tolerable intensity. The mean subcutaneous glucose concentration and mean amplitude of glycemic excursion (MAGE) were determined by flash glucose monitoring for 24 h. Changes in glycoalbumin and MAGE before and after NMES initiation were evaluated. The mean blood glucose level and MAGE after a single bout of NMES were significantly lower than those after rest. Glycoalbumin levels and echo intensity of the rectus femoris tended to decrease, but not significantly by ANOVA due to a lack in statistical power after the dropout of three patients. NMES in end-stage DKD decreased blood glucose levels during and after hemodialysis.

Prevalence of Frailty Assessed by Fried and Kihon Checklist Indexes in a Prospective Cohort Study: Design and Demographics of the Kyoto-Kameoka Longitudinal Study.

OBJECTIVE: The Kyoto-Kameoka Study was launched in 2011-2012 to identify the associations among food intake, nutritional status, physical activity, oral function, quality of life or social capital, the use of long-term care insurance (LTCI) system, and healthy lifespan in community-dwelling older people as a part of the World Health Organization Safe Community program. DESIGN: A prospective cohort study, reporting baseline demographics (cross-sectional data). SETTING AND PARTICIPANTS: We conducted 2 mailed self-administered questionnaire surveys; one is a complete population survey with a comprehensive survey of needs in the sphere of daily life (NSDL) that included 2 different frailty indexes, the Kihon Checklist (KCL) and the Fried phenotype, socioeconomic status, general and psychological health, and social relationships; followed by the more detailed Health and Nutrition Survey. A slightly modified NSDL survey was conducted again in 2013. Survival time, LTCI certification, and medical and long-term care costs after the baseline survey will be followed. RESULTS: Of 18,231 NSDL questionnaires distributed, 13,294 people responded (response rate: 72.92%; mean age 73.7 ± 6.4 and 75.1 ± 7.2 years for men and women, respectively; 12,054 people without and 1240 with LTCI certification). In people without LTCI, the proportion of robust, prefrail, and frail were 30.3%, 59.8%, and 9.9% in men and 25.3%, 64.7%, and 10.0% in women, according to the Fried index. The proportion of frail people as defined by KCL ≥7 was 30.8% in men and 33.3% in women. CONCLUSIONS: The study is the first to document frailty prevalence using both Fried and KCL measures with a complete city population survey among older Japanese in the community as a part of World Health Organization Safe Community program. The study is expected to provide valuable evidence of the effects of lifestyle habits on long-term care prevention and healthy life span.