Mitochondrial Targeted Antioxidant Intake Improves Vascular Function And Exercise Tolerance In Peripheral Artery Disease Patients

Peripheral artery disease (PAD) is an atherosclerotic disease that is associated with poor vascular function, walking impairment, and reduced quality of life. Land-based exercise therapy (LBET) is frequently recommended to improve walking and reduce symptoms. Recently, evidence has suggested that heated-water exercise therapy (HWET) is an effective intervention for PAD. However, the efficacy of LBET versus HWET in PAD patients had not been elucidated. Therefore, we sought to compare effects of LBET with HWET on cardiovascular function, exercise tolerance, physical function, and body composition in PAD patients. PAD patients ( n = 53) were recruited and randomly assigned to a LBET group ( n = 25) or HWET group ( n = 28). The LBET group performed treadmill walking, whereas the HWET group performed walking in heated water for 12 wk. Leg (legPWV) and brachial-to-ankle arterial stiffness (baPWV), blood pressure (BP), ankle-brachial index (ABI), 6-min walking distance (6MWD), claudication onset time (COT), physical function, and body composition were assessed before and after 12 wk. There were significant group-by-time interactions ( P < 0.05) for legPWV, BP, 6MWD, COT, body composition, and resting metabolic rate (RMR). Both groups significantly reduced ( P < 0.05) legPWV, BP, and body fat percentage, and HWET measures were significantly lower than LBET measures. Both groups significantly increased 6MWD, COT, and RMR, and HWET group measures were significantly greater than LBET measures. A time effect was noted for baPWV reduction in both groups ( P < 0.05). These results suggest that both LBET and HWET improve cardiovascular function, exercise tolerance, and body composition, and HWET showed considerably greater improvements compared with LBET in patients with PAD. NEW & NOTEWORTHY The results of this study reveal for the first time that although land-based exercise therapy is effective for reducing arterial stiffness and blood pressure in patients with peripheral artery disease (PAD), heated-water exercise therapy demonstrates greater benefits on vascular function. The greater improvements in muscular strength, time to onset of claudication, and exercise tolerance after heated-water exercise therapy may have clinical implications for improving quality of life in patients with PAD. The heated-water exercise therapy intervention demonstrated relatively higher exercise training adherence (∼88%) compared with the land-based exercise intervention (∼81%).

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Inorganic nitrate supplementation improves exercise tolerance and calf vascular function in patients with peripheral artery disease

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.853.2 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Joshua Bock ◽

David Treichler ◽

Kenichi Ueda ◽

William Hughes ◽

Darren Casey

Keyword(s):

Peripheral Artery Disease ◽

Vascular Function ◽

Exercise Tolerance ◽

Peripheral Artery ◽

Inorganic Nitrate ◽

Nitrate Supplementation ◽

Artery Disease

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Impacts of Aqua Aerobic Exercise on Vascular Health and Exercise Tolerance in Patients With Peripheral Artery Disease

Case Medical Research ◽

10.31525/ct1-nct03849300 ◽

2019 ◽

Author(s):

Keyword(s):

Aerobic Exercise ◽

Peripheral Artery Disease ◽

Exercise Tolerance ◽

Vascular Health ◽

Peripheral Artery ◽

Artery Disease

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Abstract 11: Effects of Canakinumab in Patients With Peripheral Artery Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.11 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Kerry S Russell ◽

Denise Yates ◽

Andrea Feller ◽

Tianke Wang ◽

Ping Chen ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Vascular Function ◽

Cardiovascular Events ◽

Ankle Brachial Index ◽

Unmet Need ◽

Walking Distance ◽

Plaque Progression ◽

Peripheral Artery ◽

Plaque Volume ◽

Artery Disease

Background: Peripheral artery disease (PAD) affects 8.5 million people in the US. PAD patients are at high risk for cardiovascular events, and their quality of life is often significantly impaired by decreased mobility. Interleukin-1β (IL-1β) may play an important role in this disease by promoting inflammatory responses that drive atherosclerotic plaque progression and impair vascular function. We sought to test whether interruption of IL-1β signaling would improve patient mobility and decrease plaque progression in the lower extremities. Methods: 38 patients (mean age 65; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive Canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. Plaque volume in the superficial femoral artery (SFA) was assessed serially using 3.0T MRI. Mobility was assessed serially using the 6-minute walk test (maximum and pain-free walking distance). Results: Canakinumab was safe and well-tolerated. 12 patients discontinued (8 placebo, 4 Canakinumab). MRI data (from 31 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA at either time point in placebo-treated patients; nor was there a change in plaque volume in the Canakinumab-treated group. There was a serial and significant improvement in placebo-adjusted maximum and pain-free walking distance observed as early as 3 months after treatment with Canakinumab (58-meter improvement over placebo in pain-free distance at 3 months, P=0.01). Two placebo-treated patients required peripheral vascular interventions due to progression of disease; however, no Canakinumab-treated patients required revascularization during the study. Canakinumab decreased markers of systemic inflammation (IL-6 and hsCRP). Conclusions: Treatment with Canakinumab may improve maximum and pain-free walk distance in patients with symptomatic PAD. In conjunction with results soon to be reported for the CANTOS trial of Canakinumab for secondary prevention of cardiovascular events, additional studies may provide support that inhibition of IL-1β signaling can improve symptoms and function in this patient population with high unmet need.

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Leg heat therapy improves perceived physical function but does not enhance walking capacity or vascular function in patients with peripheral artery disease

Journal of Applied Physiology ◽

10.1152/japplphysiol.00277.2020 ◽

2020 ◽

Vol 129 (6) ◽

pp. 1279-1289

Author(s):

Jacob C. Monroe ◽

Chen Lin ◽

Susan M. Perkins ◽

Yan Han ◽

Brett J. Wong ◽

...

Keyword(s):

Physical Function ◽

Peripheral Artery Disease ◽

Vascular Function ◽

Controlled Study ◽

Peripheral Artery ◽

Walking Capacity ◽

Heat Therapy ◽

Walking Performance ◽

Artery Disease ◽

Potent Vasoconstrictor

This is the first sham-controlled study to investigate the effects of leg heat therapy (HT) on walking performance, vascular function, and quality of life in patients with peripheral artery disease (PAD). Adherence to HT was high, and the treatment was well tolerated. Our findings revealed that HT applied with water-circulating trousers evokes a clinically meaningful increase in perceived physical function and reduces the serum concentration of the potent vasoconstrictor endothelin-1 in patients with PAD.

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00235.2020 ◽

2020 ◽

Vol 319 (2) ◽

pp. H456-H467 ◽

Cited By ~ 1

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.

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