Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease

Walker, Meegan; Høier, Birgitte; Walker, Philip J.; Schulze, Karl; Bangsbo, Jens; Hellsten, Ylva; Askew, Christopher D.

doi:10.1016/j.atherosclerosis.2015.12.029

Cited by 33 publications

(31 citation statements)

References 52 publications

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“…As illustrated in Figure 1 and further described in Table 1, lower limb vascular function assessed by the resistance artery tests RH, PLM, and ROV exhibits strong relationships with each other (r = 0.54-0.83, p < .05), supporting the notion that they reflect some of the same physiological processes (Limberg et al, 2020). This comes in agreement with data from Rossman, Groot, Garten, Witman, & Richardson (2016) and Walker et al (2016) who observed significant correlations between PLM-induced hyperemia and RH in various populations. However, as was the case for Rossman et al (2016), vascular function assessed by FMD of the superficial femoral artery was not related to the other measurements of vascular function (e.g., PLM-induced hyperemia) examined in the current study ( Figure 1, Table 1).…”

Section: Are the Various Indices Of Vascular Function Interchangablsupporting

confidence: 85%

Indices of leg resistance artery function are independently related to cycling V̇O ₂ max

et al. 2020

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Purpose While maximum blood flow influences one's maximum rate of oxygen consumption (V̇O2max), with so many indices of vascular function, it is still unclear if vascular function is related to V̇O2max in healthy, young adults. The purpose of this study was to determine if several common vascular tests of conduit artery and resistance artery function provide similar information about vascular function and the relationship between vascular function and V̇O2max. Methods Twenty‐two healthy adults completed multiple assessments of leg vascular function, including flow‐mediated dilation (FMD), reactive hyperemia (RH), passive leg movement (PLM), and rapid onset vasodilation (ROV). V̇O2max was assessed with a graded exercise test on a cycle ergometer. Results Indices associated with resistance artery function (e.g., peak flow during RH, PLM, and ROV) were generally related to each other (r = 0.47–77, p < .05), while indices derived from FMD were unrelated to other tests (p < .05). Absolute V̇O2max (r = 0.57–0.73, p < .05) and mass‐specific V̇O2max (r = 0.41–0.46, p < .05) were related to indices of resistance artery function, even when controlling for factors like body mass and sex. FMD was only related to mass‐specific V̇O2max after statistically controlling for baseline artery diameter (r = 0.44, p < .05). Conclusion Indices of leg resistance artery function (e.g., peak flow during RH, PLM, and ROV) relate well to each other and account for ~30% of the variance in V̇O2max not accounted for by other factors, like body mass and sex. Vascular interventions should focus on improving indices of resistance artery function, not conduit artery function, when seeking to improve exercise capacity.

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Section: Are the Various Indices Of Vascular Function Interchangablsupporting

confidence: 85%

Indices of leg resistance artery function are independently related to cycling V̇O ₂ max

et al. 2020

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“…Although it is becoming increasingly apparent that the vasculature is a significant source of free radicals (e.g. NADPH oxidase; Berry et al., ; Pipinos, Judge et al., ; Walker et al., ), many have proposed that damaged skeletal muscle mitochondria may be the primary source of ROS in PAD (Pipinos, Judge et al., ; Pipinos et al., ; Pipinos, Swanson et al., ). As mitochondrial dysfunction may limit muscle function and lead to loss of muscle mass in patients with PAD, understanding the pathophysiological consequences of inflammation, mitochondria‐derived ROS production and oxidative stress is clinically important.…”

Section: Discussionmentioning

confidence: 99%

Increased skeletal muscle mitochondrial free radical production in peripheral arterial disease despite preserved mitochondrial respiratory capacity

Hart

Layec

Trinity

et al. 2018

Experimental Physiology

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Skeletal muscle mitochondrial dysfunction, which is not fully explained by disease-related arterial occlusion, has been implicated in the pathophysiology of peripheral arterial disease (PAD). Therefore, this study comprehensively assessed mitochondrial respiratory function in biopsies from the gastrocnemius of 10 patients with PAD (Fontaine Stage II) and 12 healthy controls (HC). Intramuscular and systemic inflammation, mitochondria-derived reactive oxygen species (ROS) production, and oxidative stress were also assessed to better understand the mechanisms responsible for the proposed PAD-induced mitochondrial dysfunction. Interestingly, mitochondrial respiratory capacity, assessed as complex I (CI) and complex II (CII)-driven State 3 respiration, measured separately and in combination (State 3 CI+II), revealed no difference between the patients with PAD and the HC. However, mitochondria-derived ROS production was significantly elevated in PAD (HC: 1.0 ± 0.9; PAD: 4.3 ± 1.0 AU (mg tissue) ). Furthermore, patients with PAD exhibited significantly greater concentrations of the pro-inflammatory markers tumour necrosis factor α in plasma (HC: 0.9 ± 0.4; PAD: 2.0 ± 0.3 pg ml ) and interleukin 6 in both plasma (HC: 2.3 ± 0.4; PAD: 4.3 ± 0.5 pg ml ) and muscle (∼75% greater). Intramuscular oxidative stress, assessed by protein carbonyls and 4-hydroxynonenal, was significantly greater in PAD compared to HC. Ankle brachial index was significantly correlated with intramuscular inflammation, oxidative stress and mitochondria-derived ROS production. Thus, elevated intramuscular inflammation, oxidative stress and mitochondria-derived ROS production are likely to contribute to the pathophysiology of the skeletal muscle dysfunction associated with PAD, even in the presence of preserved mitochondrial respiratory function in this population.

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“…On a separate day, VL biopsies were taken from the 14 IC patients and the 10 control participants by a medical practitioner using a Bergstroem needle with suction (26,51). All biopsies were taken from the participants at rest within a 6-wk period.…”

Section: Methodsmentioning

confidence: 99%

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

Baum

Torchetti

Malik

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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(PAD). Impaired limb blood flow is a major casual factor of lower exercise tolerance in PAD but cannot entirely explain it. We hypothesized that IC is associated with structural changes of the capillary-mitochondria interface that could contribute to the reduction of exercise tolerance in IC patients. Capillary and mitochondrial morphometry were performed after light and transmission electron microscopy using vastus lateralis muscle biopsies of 14 IC patients and 10 age-matched controls, and peak power output (PPO) was determined for all participants using an incremental single-leg kneeextension protocol. Capillary density was lower (411 Ϯ 90 mm Ϫ2 vs. 506 Ϯ 95 mm Ϫ2 ; P Յ 0.05) in the biopsies of the IC patients than in those of the controls. The basement membrane (BM) around capillaries was thicker (543 Ϯ 82 nm vs. 423 Ϯ 97 nm; P Յ 0.01) and the volume density of mitochondria was lower (3.51 Ϯ 0.56% vs. 4.60 Ϯ 0.74%; P Յ 0.01) in the IC patients than the controls. In the IC patients, a higher proportion of capillaries appeared with collapsed slit-like lumen and/or swollen endothelium. PPO was lower (18.5 Ϯ 9.9 W vs. 33.5 Ϯ 9.4 W; P Յ 0.01) in the IC patients than the controls. We suggest that several structural alterations in skeletal muscle, either collectively or separately, contribute to the reduction of exercise tolerance in IC patients. capillary; morphometry; peripheral arterial disease; skeletal muscle; transmission electron microscopy PERIPHERAL ARTERIAL DISEASE (PAD) is an atherosclerotic disease characterized by stenosis or occlusion of the conduit arteries of the lower limbs (20,36). Risk factors associated with PAD include advancing age, cigarette smoking, diabetes mellitus, arterial hypertension, and disturbances in lipid metabolism (12). While many PAD patients are asymptomatic, the arterial narrowing leads to ischemia and hypoxia of the supplied tissues and in severe cases, this manifests as critical limb ischemia (CLI), usually requiring surgical interventions. Intermittent claudication (IC), which is typically described as a cramp-like muscle pain during exercise, is the most commonly reported symptom of PAD and is usually the first noted symptom of the disease.Patients with IC have limited muscular strength and endurance capacities (35), reduced cardiorespiratory fitness (V O 2 peak ), and demonstrate reduced oxygen uptake kinetics at the onset of exercise (6). They also exhibit a significantly reduced tolerance for physical activities such as walking and cycling (2, 13). This reduction in exercise tolerance leads to functional impairments that are similar to those observed in patients with heart failure (31) and contributes to their impaired mobility, reduced quality of life, and elevated risk for the development of cardiovascular complications (17).Impaired limb blood flow is commonly assumed to be the main casual factor of the reduction in exercise tolerance in PAD but cannot entirely explain it. For example, restoration of blood flow capacity with percutaneous endovascular revascularizat...

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Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease

Abstract: Background: Peripheral arterial disease (PAD) is characterised by impaired leg blood flow, which

Cited by 33 publications

References 52 publications

Indices of leg resistance artery function are independently related to cycling V̇O ₂ max

Indices of leg resistance artery function are independently related to cycling V̇O ₂ max

Increased skeletal muscle mitochondrial free radical production in peripheral arterial disease despite preserved mitochondrial respiratory capacity

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

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Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease

Abstract: Background: Peripheral arterial disease (PAD) is characterised by impaired leg blood flow, which

Cited by 33 publications

References 52 publications

Indices of leg resistance artery function are independently related to cycling V̇O 2 max

Indices of leg resistance artery function are independently related to cycling V̇O 2 max

Increased skeletal muscle mitochondrial free radical production in peripheral arterial disease despite preserved mitochondrial respiratory capacity

Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication

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Indices of leg resistance artery function are independently related to cycling V̇O ₂ max

Indices of leg resistance artery function are independently related to cycling V̇O ₂ max