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Objective: The aim of this study was to assess the effects of a single bout of maximal walking on blood and muscle nitric oxide (NO) bioavailability, oxidative stress, and inflammation in symptomatic peripheral artery disease (PAD) patients., Methods: A total of 35 men with symptomatic PAD performed a graded maximal exercise test on a treadmill (3.2 km/h, 2% increase in grade every 2 minutes). Plasma samples and gastrocnemius muscle biopsies were collected preexercise and postexercise for assessment of NO bioavailability (plasma NO and muscle, endothelial NO synthase), oxidative stress and antioxidant function (lipid peroxidation [LPO], catalase [CAT], and superoxide dismutase), and inflammation (interleukin-6, C-reactive protein, tumor necrosis factor-α, intercellular adhesion molecules, and vascular adhesion molecules). The effects of the walking exercise were assessed using paired t tests or Wilcoxon tests., Results: After maximal walking, plasma NO and LPO were unchanged (P > .05), plasma CAT decreased, and all blood inflammatory markers increased (all P ≤ .05). In the disease-affected skeletal muscle, endothelial NO synthase, CAT, LPO, and all inflammatory markers increased, whereas superoxide dismutase decreased (all P ≤ .05)., Conclusion: In patients with symptomatic PAD, maximal exercise induces local and systemic impairments, which may play a key role in atherogenesis. Exercise strategies that avoid maximal effort may be important to reduce local and systemic damage and enhance clinical benefits., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although maximal and submaximal walking are recommended for patients with peripheral artery disease (PAD), performing these exercises may induce different physiological responses., Objectives: To compare the acute effects of maximal and submaximal walking on post-exercise cardiovascular function, regulation, and associated pathophysiological processes in patients with symptomatic PAD., Methods: Thirty male patients underwent 2 sessions: maximal walking (Gardner's protocol) and submaximal walking (15 bouts of 2 minutes of walking separated by 2 minutes of upright rest). In each session, blood pressure (BP), heart rate (HR), cardiac autonomic modulation (HR variability), forearm and calf blood flows (BF), vasodilatory capacity (reactive hyperemia), nitric oxide (NO), oxidative stress (lipid peroxidation), and inflammation (four markers) were measured pre- and post-walking. ANOVAs were employed, and p < 0.05 was considered significant., Results: Systolic and mean BP decreased after the submaximal session, but they increased after the maximal session (interactions, p < 0.001 for both). Diastolic BP did not change after the submaximal session (p > 0.05), and it increased after maximal walking (interaction, p < 0.001). HR, sympathovagal balance, and BF increased similarly after both sessions (moment, p < 0.001, p = 0.04, and p < 0.001, respectively), while vasodilatory capacity, NO, and oxidative stress remained unchanged (p > 0.05). Vascular and intercellular adhesion molecules increased similarly after both maximal and submaximal walking sessions (moment, p = 0.001)., Conclusions: In patients with symptomatic PAD, submaximal, but not maximal walking reduced post-exercise BP, while maximal walking maintained elevated cardiac overload during the recovery period. On the other hand, maximal and submaximal walking sessions similarly increased post-exercise HR, cardiac sympathovagal balance, and inflammation, while they did not change post-exercise NO bioavailability and oxidative stress.

Objective: This study examined the impact of submaximal walking training (WT) on local and systemic nitric oxide (NO) bioavailability, inflammation, and oxidative stress in patients with intermittent claudication (IC)., Methods: The study employed a randomised, controlled, parallel group design and was performed in a single centre. Thirty-two men with IC were randomly allocated to two groups: WT (n = 16, two sessions/week, 15 cycles of two minutes walking at an intensity corresponding to the heart rate obtained at the pain threshold interspersed by two minutes of upright rest) and control (CO, n = 16, two sessions/week, 30 minutes of stretching). NO bioavailability (blood NO and muscle nitric oxide synthase [eNOS]), redox homeostasis (catalase [CAT], superoxide dismutase [SOD], lipid peroxidation [LPO] measured in blood and muscle), and inflammation (interleukin-6 [IL-6], C-reactive protein [CRP], tumour necrosis factor α [TNF-α], intercellular adhesion molecules [ICAM], vascular adhesion molecules [VCAM] measured in blood and muscle) were assessed at baseline and after 12 weeks., Results: WT statistically significantly increased blood NO, muscle eNOS, blood SOD and CAT, and muscle SOD and abolished the increase in circulating and muscle LPO observed in the CO group. WT decreased blood CRP, ICAM, and VCAM and muscle IL-6 and CRP and eliminated the increase in blood TNF-α and muscle TNF-α, ICAM and VCAM observed in the CO group., Conclusion: WT at an intensity of pain threshold improved NO bioavailability and decreased systemic and local oxidative stress and inflammation in patients with IC. The proposed WT protocol provides physiological adaptations that may contribute to cardiovascular health in these patients., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: The aim of this study is to identify, in patients with peripheral artery disease and intermittent claudication (IC), the reproducibility of heart rate (HR), blood pressure (BP), rate pressure product, heart rate variability (HRV), and forearm and calf blood flow (BF) and vasodilatory assessments., Methods: Twenty-nine patients with IC underwent test and retest sessions, 8-12 days apart. During each session, HR, BP, HRV, BF, and vasodilatory responses were measured by electrocardiogram, auscultation, spectral analysis of HRV (low frequency, LF R-R ; high frequency, HF R-R ), and strain gauge plethysmography (baseline BF, post-occlusion BF, post-occlusion area under the curve). Reproducibility was determined by intra-class correlation coefficient (ICC), typical error, coefficient of variation (CV), and limits of agreement., Results: The ICC for HR and BP was >0.8 with CV <9%. For most HRV measures, ICC was >0.9 while CV was <7%, except for LF/HF (ICC = 0.737, CV = 93.8%). The ICC for forearm and calf baseline BF assessments was >0.9 while CV was <19%; variable ICC and CV for vasodilatory responses were exhibited for calf (0.653-0.770, 35.2-37.7%) and forearm (0.169-0.265, 46.2-55.5%)., Conclusions: In male patients with IC, systemic hemodynamics (HR and BP), cardiac autonomic modulation (LF R-R and HF R-R ), and forearm and calf baseline BF assessments exhibited excellent reproducibility, whereas the level of reproducibility for vasodilatory responses were moderate to poor. Assessment reproducibility has highlighted appropriate clinical tools for the regular monitoring of disease/intervention progression in patients with IC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Postexercise heart rate recovery (HRR) is a non-invasive tool for cardiac autonomic function assessment. Reproducibility of HRR has been established in healthy subjects; however, no study has evaluated this reproducibility in clinical populations who may present autonomic dysfunction. Patients with peripheral artery disease and intermittent claudication (IC) often present altered cardiac autonomic function and HRR could be an interesting tool for evaluating autonomic responses to interventions in this population. Therefore, the reproducibility of HRR should be determined in this specific population., Objective: To determine the reproducibility of HRR indices in patients with IC., Methods: Nineteen men with IC underwent two repeated maximal treadmill tests. Raw HR and relative HRR (difference to exercise peak) indices measured at 30, 60, 120, 180, 240 and 300s of recovery were evaluated. The presence of systematic bias was assessed by comparing test and retest mean values via paired t-test. Reliability was assessed by intraclass correlation coefficient (ICC), and agreement by typical error (TE), coefficient of variation (CV) and minimal detectable difference (MDD)., Results: There were no significant differences between the test and retest values of all raw HR and relative HRR indices (P ≥ 0·05), except for HR120s (P = 0·032). All indices exhibited excellent reliability (ICC ≥ 0·78). Raw HR and relative HRR indices showed TEs ≤ 6·4 bpm and MDDs ≤ 17·8 bpm. In addition, all indices showed CVs ≤ 13·2%, except HRR30s (CV = 45·6%)., Conclusions: The current results demonstrated that most HRR indices were highly reproducible with no systematic error, excellent reliability and good agreement in patients with IC following maximal graded exercise., (© 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

This study determined the reproducibility of post-exercise hypotension (PEH) calculated by the following methods: PEH&#95;I=post-exercise BP - pre-exercise BP; PEH&#95;II=post-exercise BP - post-control BP; and PEH&#95;III=[(post-exercise BP - pre-exercise BP)-(post-control BP - pre-control BP)]. Twenty-five participants underwent four sessions divided in two blocks (test and retest). Each block consisted of one exercise and one control session. BP pressure was measured before and after the interventions. The presence of systematic error (paired t-tests), reliability [intraclass coefficient correlation (ICC)], and agreement [typical error (TE) and minimal detectable difference (MDD)] were evaluated. PEHs calculated by the three methods were similar between test and retest. For systolic PEH, ICC was>0.74, TE ranged from 2.6 to 4.6 mmHg and MDD from 7.2 to 12.8 mmHg for the three methods. For diastolic PEH, ICC was<0.48, TE ranged from 3.5 to 5.6 mmHg and MDD from 9.8 to 15.4 mmHg for the three methods. Thus, systolic PEH calculated by the three methods has good/excellent reliability, while diastolic PEH has fair/poor reliability. Regarding agreement, TE and MDD varied among the methods, which implies that the specific parameters given for each method should be used to estimate sample sizes for studies and the minimal individual difference considered real when comparing PEHs., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: This study investigated the effects of walking training (WT) on cardiovascular function and autonomic regulation in patents with intermittent claudication (IC)., Design: Randomized controlled trial., Methods: Forty-two male patients with IC (≥50years) were randomly allocated into two groups: control (CG, n=20, 30min of stretching exercises) and WT (WTG, n=22, 15 bouts of 2min of walking interpolated by 2min of upright rest-walking intensity was set at the heart rate of pain threshold). Both interventions were performed twice/week for 12 weeks. Walking capacity (maximal treadmill test), blood pressure (auscultatory), cardiac output (CO 2 rebreathing), heart rate (ECG), stroke volume, systemic vascular resistance, forearm and calf vascular resistance (plethysmography), and low (LF) and high frequency (HF) components of heart rate variability and spontaneous baroreflex sensitivity were measured at baseline and after 12 weeks of the study., Results: WT increased total walking distance (+302±85m, p=0.001) and spontaneous baroreflex sensitivity (+2.13±1.07ms/mmHg, p=0.02). Additionally, at rest, WT decreased systolic and mean blood pressures (-10±3 and -5±2mmHg, p=0.001 and p=0.01, respectively), cardiac output (-0.37±0.24l/min, p=0.03), heart rate (-4±2bpm, p=0.001), forearm vascular resistance (-8.5±2.8U, p=0.02) and LF/HF (-1.24±0.99, p=0.001). No change was observed in the CG., Conclusions: In addition to increasing walking capacity, WT improved cardiovascular function and autonomic regulation in patients with IC., (Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Objective: Patients with intermittent claudication (IC) often have high blood pressure (BP), which increases their cardiovascular risk. However, whether walking capacity is associated with BP levels in patients with IC remains unknown. Therefore, this study was designed to investigate whether the total walking distance is associated with ambulatory BP in patients with IC., Participants and Methods: This was a cross-sectional study of 75 patients with IC (58 men; 17 women). A maximal treadmill test (Gardner protocol) was performed to assess total walking distance in these patients. Furthermore, ambulatory BP, heart rate, rate-pressure product, and BP load were obtained over a 24-h period. One-way analysis of variance and multiple linear regression were carried out., Results: Walking capacity was correlated negatively with the following: (i) asleep systolic BP, diastolic BP, mean BP and heart rate; (ii) 24-h, awake and asleep RPP; and (iii) awake and asleep systolic BP load (all P<0.05). These associations occurred irrespective of confounders such as age, sex, BMI, smoking status, and number of antihypertensive medications., Conclusion: A better walking capacity is associated with lower ambulatory BP parameters in patients with IC.

Purpose: Maximal and submaximal parameters assessed during treadmill tests are used to prescribe exercise training and assess exercise-induced adaptations in patients with intermittent claudication (IC). Although reproducibility of maximal parameters is well documented, the reproducibility of submaximal is not clear. The aim of this study was to identify the reproducibility (reliability and agreement) of heart rate (HR) and oxygen uptake ((Equation is included in full-text article.)O2) measured at the anaerobic (AT) and the pain (PT) thresholds assessed during a maximal test in patients with IC., Methods: Twenty male patients with IC underwent 2 cardiopulmonary treadmill tests to maximal pain. The HR and (Equation is included in full-text article.)O2 at the AT and PT were identified, and differences between repeat tests were compared. Reliability was determined by intraclass coefficient correlation (ICC). Agreement was assessed by coefficient of variation (CV), standard error of measurement (SEM), smallest detectable difference (SDD), and limits of agreement (LOA)., Results: The (Equation is included in full-text article.)O2 at AT and PT exhibited moderate reliability and moderate/good agreement (ICC = 0.73 and 0.70; CV = 9.6% and 11.1%, respectively). The HR at the AT and PT exhibited high reliability and good agreement (ICC = 0.87 and 0.92; SEM = 3.9 and 3.2 bpm; SDD = 10.8 and 8.8 bpm, respectively). The LOA for (Equation is included in full-text article.)O2 at AT and PT were ≤20% and for HR ≤11 bpm., Conclusions: The (Equation is included in full-text article.)O2 and HR measured at the AT and PT were moderately to highly reproducible in male patients with IC. The HR and (Equation is included in full-text article.)O2 at AT and PT may be used to establish training intensity and evaluate training effectiveness for these patients in clinical practice and research.

Increased oxidative stress and inflammation contribute to impaired walking capacity and endothelial dysfunction in patients with intermittent claudication (IC). The goal of the study was to determine the effects of oral treatment with the antioxidant N-acetylcysteine (NAC) on walking capacity, leg postocclusive reactive hyperemia, circulating levels of inflammatory mediators, and whole blood expression of angiogenic mediators in patients with IC. Following a double-blinded randomized crossover design, 10 patients with IC received NAC (1,800 mg/day for 4 days plus 2,700 mg before the experimental session) and placebo (PLA) before undergoing a graded treadmill exercise test. Leg postocclusive reactive hyperemia was assessed before and after the test. Blood samples were taken before and after NAC or PLA ingestions and 5 and 30 min after the exercise test for the analysis of circulating inflammatory and angiogenic markers. Although NAC increased the plasma ratio of reduced to oxidized glutathione, there were no differences between experimental sessions for walking tolerance and postocclusive reactive hyperemia. Plasma concentrations of soluble vascular cell adhesion protein-1, monocyte chemotactic protein-1, and endothelin-1 increased similarly following maximal exercise after PLA and NAC (P < 0.001). Whole blood expression of pro-angiogenic microRNA-126 increased after maximal exercise in the PLA session, but treatment with NAC prevented this response. Similarly, exercise-induced changes in whole blood expression of VEGF, endothelial nitric oxide synthase and phosphatidylinositol 3-kinase R2 were blunted after NAC. In conclusion, oral NAC does not increase walking tolerance or leg blood flow in patients with IC. In addition, oral NAC prevents maximal exercise-induced increase in the expression of circulating microRNA-126 and other angiogenic mediators in patients with IC., (Copyright © 2015 the American Physiological Society.)

Objective: To investigate barriers to physical activity related to the sociodemographic comorbidities and clinical variables of patients with intermittent claudication., Design: Cross-sectional study., Setting: Ambulatory care., Participants: The medical histories of patients (N=145) aged ≥50 years with intermittent claudication were examined., Interventions: Not applicable., Main Outcome Measures: Sociodemographic data (sex, race, level of education, socioeconomic status, marital status), comorbidities (overweight, hypertension, dyslipidemia, diabetes, currently smoking, heart disease), and clinical variables (initial claudication distance, total walking distance, ankle-brachial index). Information on personal and environmental barriers was obtained by questionnaire., Results: Low economic status was most associated with "being afraid of falling" (odd ratios [OR]=2.22; 95% confidence interval [CI], 1.08-4.54). Low education level was most associated with "lack of street pedestrian crossing" (OR=3.34; 95% CI, 1.48-7.52). Diabetes was associated with lack of energy (OR=3.38; 95% CI, 1.68-6.79) and other medical conditions (eg, arthritis, angina) (OR=3.44; 95% CI, 1.65-7.16). Ankle brachial index was associated with "some difficulty in getting to a place where physical activity can be performed" (OR=2.75; 95% CI, 1.22-6.21). Walking capacity was strongly associated with barriers relating to leg pain (OR=7.39; 95% CI, 1.66-32.88)., Conclusions: Older patients, those with a low education level, patients with diabetes, low ankle brachial index, and those with a lower walking capacity are more likely to experience barriers to physical activity., (Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The main barriers reported by the patients with claudication are related to claudication symptoms. However, it remains unclear whether these barriers are associated with physical activity levels in these patients., Purpose: The aim of this study was to analyze the barriers to and the factors associated with physical activity (PA) in intermittent claudication (IC) patients., Methods: The sample included 150 IC Brazilian patients and mean age 64 ± 9 years old. Sociodemographic factors, comorbid conditions and cardiovascular risk factors, personal and environmental barriers to PA, and walking capacity (claudication onset distance-COD and peak walking distance-PWD) were obtained. PA was assessed using a pedometer over seven consecutive days., Results: Patients performed 6,041 ± 3,166 steps/day. The most prevalent personal and environmental barriers to PAs were exercise-induced pain and the presence of obstacles that aggravate the leg pain. Multiple linear regression showed that level of PA was inversely associated with age (β = -81.13; p < 0.001), lack of green areas (β = -1363.54; p < 0.001), and positively associated with PWD (β = 3.07; p < 0.001)., Conclusion: Older IC patients who live in neighborhoods that lack green areas to walk in, and who have poor walking capacity present lower levels of PA.