Body mass-normalized moderate dose of dietary nitrate intake improves endothelial function and walking capacity in patients with peripheral artery disease

2021 ◽  
Author(s):  
Elizabeth J. Pekas ◽  
TeSean K. Wooden ◽  
Saantosh Yadav ◽  
Song-Young Park
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Function ◽  
Body Mass ◽  
Walking Distance ◽  
Moderate Dose ◽  
Peripheral Artery ◽  
Oxygen Utilization ◽  
Muscle Oxygen ◽  
Walking Capacity ◽  
Artery Disease

Peripheral artery disease (PAD) is characterized by the accumulation of atherosclerotic plaques in the lower extremity conduit arteries, which impairs blood flow and walking capacity. Dietary nitrate has been used to reduce blood pressure (BP) and improve walking capacity in PAD. However, a standardized dose for PAD has not been determined. Therefore, we sought to determine the effects of a body mass-normalized moderate dose of nitrate (0.11 mmol nitrate/kg) as beetroot juice on serum nitrate/nitrite, vascular function, walking capacity, and tissue oxygen utilization capacity in patients with PAD. 11 patients with PAD received either nitrate supplement or placebo in a randomized crossover design. Total serum nitrate/nitrite, resting BP, brachial and popliteal artery endothelial function (flow-mediated dilation, FMD), arterial stiffness (pulse-wave velocity, PWV), augmentation index (AIx), maximal walking distance and time, claudication onset time, and skeletal muscle oxygen utilization were measured pre-and-post-nitrate and placebo intake. There were significant group x time interactions (p<0.05) for serum nitrate/nitrite, FMD, BP, walking distance and time, and skeletal muscle oxygen utilization. The nitrate group showed significantly increased serum nitrate/nitrite (Δ1.32μM), increased brachial and popliteal FMD (Δ1.3% and Δ1.7%, respectively), reduced peripheral and central systolic BP (Δ-4.7mmHg and Δ-8.2mmHg, respectively), increased maximal walking distance (Δ92.7m) and time (Δ56.3s), and reduced deoxygenated hemoglobin during walking. There were no changes in PWV, AIx, or claudication (p>0.05). These results indicate that a body-mass normalized moderate dose of nitrate may be effective and safe for reducing BP, improving endothelial function, and improving walking capacity in patients with PAD.

Abstract 319: Effects of Muscle Stretching on Flow-Mediated Dilation of Popliteal Artery in Patients With Peripheral Artery Disease

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Kazuki Hotta ◽  
Wayne B Batchelor ◽  
James Graven ◽  
Vishal Dahya ◽  
Thomas E Noel ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Popliteal Artery ◽  
Calf Muscle ◽  
Walking Distance ◽  
Flow Mediated Dilation ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Peripheral Artery ◽  
Muscle Stretching ◽  
Artery Disease

Patients with peripheral artery disease (PAD) frequently have walking impairment due to lower extremity claudication. Our preliminary results in a rat model of aging indicate that a program of daily calf muscle stretching improves endothelium-dependent dilation of soleus muscle arterioles and increases soleus muscle blood flow during exercise. However, the effects of muscle stretching on the function of arteries supplying the legs of PAD patients is unknown. We hypothesized that daily calf muscle stretching improves vascular endothelial function and walking distance in PAD patients. To test our hypothesis, a randomized, non-blinded, crossover study was performed. Four weeks of muscle stretching (30 min/d, 5 days/wk) and 4 weeks of sedentary lifestyle (no stretching) were performed in random order. Thirteen patients with PAD participated in this study (71 ± 2 years old; 7 males and 6 females). During the stretching intervention both ankle joints were maintained at 15o of dorsiflexion using ankle dorsiflexion splints to stretch their calf muscles at home. Flow-mediated dilation (FMD; dilation to post-occlusion reactive hyperemia) and nitroglycerin-induced dilation (dilation to sublingual 0.4 mg nitroglycerin) of the popliteal artery were measured after 4 weeks of muscle stretching and after the no stretching period using ultrasound. A six-minute walk test was also performed to obtain walking distance. After 4 weeks of muscle stretching, FMD and 6-minute walking distance significantly improved as compared to the values measured after 4 weeks of no stretching (FMD: 5.2 ± 0.6 % vs. 3.7 ± 0.4 %, P=0.003 stretching vs. no stretching, 6-minute walking distance: 355 ± 32 m vs. 311 ± 31 m, P=0.007, stretching vs. no stretching; mean ± SE). No difference in nitroglycerin-induced dilation was found between groups (10.9 ± 1.4 vs. 9.9 ± 1.1 %, P=0.54, stretching vs. no stretching). Percentage change of walking distance (%change = [(stretching - no stretching) / no stretching] x 100) significantly correlated with the %change of FMD (R 2 =0.65, P=0.03). These results indicate that static calf muscle stretching enhances vascular endothelial function of the popliteal artery, contributing to improvement of walking tolerance in PAD patients.

scholarly journals Acute mitochondrial antioxidant intake improves endothelial function, antioxidant enzyme activity, and exercise tolerance in patients with peripheral artery disease

2020 ◽  
Vol 319 (2) ◽  
pp. H456-H467 ◽  
Author(s):  
Song-Young Park ◽  
Elizabeth J. Pekas ◽  
Ronald J. Headid ◽  
Won-Mok Son ◽  
TeSean K. Wooden ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Peripheral Artery Disease ◽  
Oral Intake ◽  
Muscle Performance ◽  
Vascular Endothelial ◽  
Peripheral Artery ◽  
Walking Capacity ◽  
Antioxidant Intake ◽  
Artery Disease ◽  
First Time

The results of this study reveal for the first time that acute oral intake of mitochondrial-targeted antioxidant (MitoQ, 80 mg) is effective for improving vascular endothelial function and superoxide dismutase in patients with peripheral artery disease (PAD). Acute MitoQ intake is also effective for improving maximal walking capacity and delaying the onset of claudication in patients with PAD. These findings suggest that the acute oral intake of MitoQ-mediated improvements in vascular mitochondria play a pivotal role for improving endothelial function, the redox environment, and skeletal muscle performance in PAD.

Adaptation of external counterpulsation based on individual shear rate therapy improves endothelial function and claudication distance in peripheral artery disease

VASA ◽  
2016 ◽  
Vol 45 (4) ◽  
pp. 317-324 ◽  
Author(s):  
Eva-Elina Buschmann* ◽  
Michele Brix* ◽  
Lulu Li ◽  
Janke Doreen ◽  
Andreas Zietzer ◽  
...  
Keyword(s):  
Shear Rate ◽  
Endothelial Function ◽  
Walking Distance ◽  
Peripheral Perfusion ◽  
Peripheral Artery ◽  
Doppler Flow ◽  
External Counterpulsation ◽  
Non Invasive ◽  
Artery Disease

Abstract. Background: External counterpulsation therapy enhances blood flow and was shown to improve endothelial function and quality of life in coronary artery disease patients. However, high pressures of up to 300 mmHg may lead to malperfusion of the ischaemic limb. To improve the clinical outcome of patients with peripheral artery disease (PAD), we adjusted external counterpulsation and developed a novel non-invasive approach termed individual shear rate therapy (ISRT). Patients and methods: In the present study, 14 patients with a Fontaine stage IIb and femoral-popliteal PAD underwent 30 hours of ISRT over 5 weeks. For ISRT, individual treatment pressures that do not exceed 160 mmHg were assessed by Doppler flow parameters during counterpulsation (individual shear rate diagnosis) in order to enhance and maximise peripheral perfusion. The study aimed to enhance peripheral perfusion and evaluate the primary clinical endpoint endothelial function, as well as to perform preliminary analysis of the ankle brachial index (ABI) and walking distance. Results: Doppler flow measurements in the lower limb (ankle) validated that maximum blood flow velocity during systole and acceleration doubled during ISRT. Study results demonstrated that long-term ISRT significantly increased flow-mediated dilation (FMD) in the brachial artery (0.13+/- 0.09 mm to 0.38+/- 0.05 mm; p < 0.05), while nitromediated dilation (0.36+/- 0.10 mm to 0.45+/- 0.08 mm) remained and common femoral artery FMD did not reach statistical significance (0.38+/- 0.08 mm to 0.67+/- 0.19 mm; p<0.05). Initial claudication distance considerably improved for all patients after 30 hours of ISRT (92.6 +/- 8.2 metres to 280+/- 101.3 metres, p<0.05), just like the absolute claudication distance, which showed a more than 2.5-fold increase (167.8+/- 18.1 metres to 446.7+/- 133.3 metres; p<0.05). The ABI did not improve (0.58+/- 0.03 to 0.65+/- 0.04). Conclusions: Our data demonstrate that long-term ISRT is a potential novel non-invasive treatment to improve endothelial function and absolute pain-free walking distance for PAD patients.

Skeletal muscle expression of adipose-specific phospholipase in peripheral artery disease

2020 ◽  
Vol 25 (5) ◽  
pp. 401-410
Author(s):  
Caitlin Parmer ◽  
Ana Luisa De Sousa-Coelho ◽  
Henry S Cheng ◽  
Grace Daher ◽  
Alison Burkart ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Peripheral Artery Disease ◽  
Muscle Metabolism ◽  
Diabetic Mice ◽  
Peripheral Artery ◽  
Artery Ligation ◽  
Muscle Gene Expression ◽  
Walking Capacity ◽  
Artery Disease

Flow-limiting atherosclerotic lesions of arteries supplying the limbs are a cause of symptoms in patients with peripheral artery disease (PAD). Musculoskeletal metabolic factors also contribute to the pathophysiology of claudication, which is manifest as leg discomfort that impairs walking capacity. Accordingly, we conducted a case–control study to determine whether skeletal muscle metabolic gene expression is altered in PAD. Calf skeletal muscle gene expression of patients with PAD and healthy subjects was analyzed using microarrays. The top-ranking gene differentially expressed between PAD and controls (FDR < 0.001) was PLA2G16, which encodes adipose-specific phospholipase A2 (AdPLA) and is implicated in the maintenance of insulin sensitivity and regulation of lipid metabolism. Differential expression was confirmed by qRT-PCR; PLA2G16 was downregulated by 68% in patients with PAD ( p < 0.001). Expression of Pla2g16 was then measured in control (db/+) and diabetic (db/db) mice that underwent unilateral femoral artery ligation. There was significantly reduced expression of Pla2g16 in the ischemic leg of both control and diabetic mice (by 51%), with significantly greater magnitude of reduction in the diabetic mice (by 79%). We conclude that AdPLA is downregulated in humans with PAD and in mice with hindlimb ischemia. Reduced AdPLA may contribute to impaired walking capacity in patients with PAD via its effects on skeletal muscle metabolism. Further studies are needed to fully characterize the role of AdPLA in PAD and to investigate its potential as a therapeutic target for alleviating symptoms of claudication.

scholarly journals Blood pressure and leg deoxygenation are exaggerated during treadmill walking in patients with peripheral artery disease

2017 ◽  
Vol 123 (5) ◽  
pp. 1160-1165 ◽  
Author(s):  
Amanda J. Miller ◽  
J. Carter Luck ◽  
Danielle Jin-Kwang Kim ◽  
Urs A. Leuenberger ◽  
David N. Proctor ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Peripheral Arterial Disease ◽  
Healthy Subjects ◽  
Arterial Disease ◽  
Treadmill Walking ◽  
Peripheral Artery ◽  
Muscle Oxygen ◽  
Artery Disease ◽  
Peripheral Arterial

The purpose of this study was to investigate blood pressure (BP) and leg skeletal muscle oxygen saturation (Smo2) during treadmill walking in patients with peripheral artery disease (PAD) and healthy subjects. Eight PAD patients (66 ± 8 yr, 1 woman) and eight healthy subjects (65 ± 7 yr, 1 woman) walked on a treadmill at 2 mph (0.89 m/s). The incline increased by 2% every 2 min, from 0 to 15% or until maximal discomfort. BP was measured every 2 min with an auscultatory cuff. Heart rate (HR) was recorded continuously with an ECG. Smo2 in the gastrocnemius muscle was measured on each leg using near-infrared spectroscopy. The change in systolic BP from seated to peak walking time (PWT) was greater in PAD (healthy: 23 ± 9 vs. PAD: 44 ± 19 mmHg, P = 0.007). HR was greater in PAD patients compared with controls at PWT ( P = 0.011). The reduction in Smo2 (PWT − seated) was greater in PAD (healthy: 15 ± 12 vs. PAD: 49 ± 5%, P < 0.001) in the most affected leg and in the least affected leg (healthy: 12 ± 11 vs. PAD: 32 ± 18%, P = 0.003). PAD patients have an exaggerated decline in leg Smo2 during walking compared with healthy subjects, which may elicit the exaggerated rise in BP and HR during walking in PAD. NEW & NOTEWORTHY This is the first study to simultaneously measure skeletal muscle oxygen saturation and blood pressure (BP) during treadmill exercise in patients with peripheral arterial disease. We found that BP and leg deoxygenation responses to slow-paced, graded treadmill walking are greater in patients with peripheral arterial disease compared with healthy subjects. These data may help explain the high cardiovascular risk in patients with peripheral arterial disease.

scholarly journals Supervised Resistance Training on Functional Capacity, Muscle Strength and Vascular Function in Peripheral Artery Disease: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (10) ◽  
pp. 2193
Author(s):  
Elizabeth E. Blears ◽  
Jessica K. Elias ◽  
Christian Tapking ◽  
Craig Porter ◽  
Victoria G. Rontoyanni
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Muscle Strength ◽  
Functional Capacity ◽  
Vascular Function ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Peripheral Artery ◽  
Walking Capacity ◽  
Artery Disease

Supervised resistance training appears to be a promising alternative exercise modality to supervised walking in patients with peripheral artery disease (PAD). This meta-analysis examined the efficacy of supervised RT for improving walking capacity, and whether adaptations occur at the vascular and/or skeletal muscle level in PAD patients. We searched Medline, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) in PAD patients testing the effects of supervised RT for ≥4 wk. on walking capacity, vascular function, and muscle strength. Pooled effect estimates were calculated and evaluated using conventional meta-analytic procedures. Six RCTs compared supervised RT to standard care. Overall, supervised RT prolonged claudication onset distance during a 6-min walk test (6-MWT) (101.7 m (59.6, 143.8), p < 0.001) and improved total walking distance during graded treadmill walking (SMD: 0.67 (0.33, 1.01), p < 0.001) and the 6-MWT (49.4 m (3.1, 95.6), p = 0.04). Five RCTS compared supervised RT and supervised intermittent walking, where the differences in functional capacity between the two exercise modalities appear to depend on the intensity of the exercise program. The insufficient evidence on the effects of RT on vascular function and muscle strength permitted only limited exploration. We conclude that RT is effective in prolonging walking performance in PAD patients. Whether RT exerts its influence on functional capacity by promoting blood flow and/or enhancing skeletal muscle strength remains unclear.

Sodium nitrite in patients with peripheral artery disease and diabetes mellitus: Safety, walking distance and endothelial function

2013 ◽  
Vol 19 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Emile R Mohler ◽  
William R Hiatt ◽  
Heather L Gornik ◽  
Christopher G Kevil ◽  
Arshed Quyyumi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Function ◽  
Peripheral Artery Disease ◽  
Sodium Nitrite ◽  
Walking Distance ◽  
Peripheral Artery ◽  
Artery Disease

Abstract 251: Effects of n-3 Fatty Acids Supplementation on Endothelial Function and Inflammation in Peripheral Artery Disease: The OMEGA-PAD Trial

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Marlene Grenon ◽  
Christopher Owens ◽  
Hugh Alley ◽  
Karen Chong ◽  
Priscilla Yen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endothelial Function ◽  
San Francisco ◽  
Peripheral Artery Disease ◽  
Ankle Brachial Index ◽  
Walking Distance ◽  
Omega 3 ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Background Patients with peripheral artery disease (PAD) have an increased risk for cardiovascular events, likely related to inflammation and impaired endothelial function. n-3 polyunsaturated fatty acids (n3-PUFAs) have been shown to improve endothelial function and reduce inflammation in other cohorts. We hypothesized that n3-PUFAs would improve endothelial function and the inflammatory profile in patients with PAD. Methods This is a randomized, double-blind, placebo-controlled trial: the OMEGA-PAD trial ( NCT01310270 ). Eighty patients aged 50 and more with intermitted claudication and an ankle-brachial index (ABI) of <0.9 presenting to vascular surgery clinic at the Veterans Affairs Medical Center in San Francisco will be randomized to n3-PUFAs 2.2 g orally twice daily (total of 4.4gm/day) or a matched placebo for 1 month. Outcome measurements are done at baseline and after 1 month. The primary endpoint is a change in endothelial function measured by brachial artery flow mediated, endothelium-dependent vasodilation (FMD). Secondary endpoints include a change in inflammatory markers (C-reactive protein, IL-6, sICAM-1 and TNF-α), improvement in lipid profile (LDL, triglycerides, HDL), blood pressure and walking distance by questionnaire. The omega-3 index will be measured to ensure physiological treatment effect. Results Recruitment for the OMEGA-PAD trial started in April 2011. Fifty male veterans have been enrolled and randomized. The mean age is 67 ± 9 years. Mean index limb ABI is 0.8 ± 0.2. CAD is present in 36%, hypertension in 92%, and diabetes mellitus in 32%. 47% are current smokers and 45% are former smokers. Mean HgA1c is 8±1, LDL 93±37 mg/dL, triglycerides 160±98 mg/dL and HDL 43 ±12 mg/dL. Baseline brachial FMD is 7±4% indicating an overall impairment of endothelial function in this cohort. The inflammatory burden of this cohort is substantial as evidenced by hsCRP 5±5 mg/L. The baseline omega-3 index is 5±2%. Conclusions The OMEGA-PAD trial will test the novel hypothesis that n3-PUFAs supplementation improves functional and inflammatory parameters in a cohort at high vascular risk. The results of this study will provide valuable mechanistic insight into PUFAs as well as inform on this class of agents for cardiovascular outcome trials.

Telmisartan improves absolute walking distance and endothelial function in patients with peripheral artery disease

2010 ◽  
Vol 99 (12) ◽  
pp. 787-794 ◽  
Author(s):  
A. R. Zankl ◽  
B. Ivandic ◽  
M. Andrassy ◽  
H. C. Volz ◽  
U. Krumsdorf ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Peripheral Artery Disease ◽  
Walking Distance ◽  
Peripheral Artery ◽  
Artery Disease

Individual Differences in Response to Supervised Exercise Therapy for Peripheral Artery Disease

2020 ◽  
pp. 019394592097747
Author(s):  
Mary O. Whipple ◽  
Erica N. Schorr ◽  
Kristine M.C. Talley ◽  
Julian Wolfson ◽  
Ruth Lindquist ◽  
...  
Keyword(s):  
Older Adults ◽  
Peripheral Artery Disease ◽  
Exercise Therapy ◽  
Poor Response ◽  
Walking Distance ◽  
Peripheral Artery ◽  
Meaningful Improvement ◽  
Supervised Exercise ◽  
Patient Reported ◽  
Artery Disease

Nonresponse to exercise has been extensively examined in young athletes but is seldom reported in studies of aerobic exercise interventions in older adults. This study examined the prevalence of nonresponse and poor response to exercise in functional and quality of life outcomes and response patterns between and among older adults undergoing 12-weeks of supervised exercise therapy for the management of peripheral artery disease ( N = 44, mean age 72.3 years, 47.7% female). The prevalence of nonresponse (no change/decline in performance) in walking distance was 31.8%. The prevalence of poor response (lack of a clinically meaningful improvement) was 43.2%. Similar patterns of response were observed in both objective and patient-reported measures of physical function. All participants improved in at least one outcome; only two participants improved in all measured outcomes. Additional research should examine modifiable predictors of response to inform programming and maximize an individual’s potential benefit from exercise therapy.

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