Skeletal muscle mitochondrial ATP production rate and walking performance in peripheral arterial disease

Hou, Xiang-Yu; Green, S.; Askew, Christopher D.; Barker, Glenn A.; Green, A.; Walker, Philip J.

doi:10.1046/j.1475-097x.2002.00423.x

Cited by 49 publications

(53 citation statements)

References 34 publications

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“…The observation that PPO was lower in the IC patients than the controls is consistent with the limited muscular strength and endurance capacities of IC patients previously described (13,35), and the well-established reduction in their tolerance for physical activities such as walking and cycling (2,28). Several studies have investigated the mechanisms of exercise intolerance in IC patients.…”

Section: Discussionsupporting

confidence: 85%

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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Section: Discussionsupporting

confidence: 85%

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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“…Previous studies have shown that exercise tolerance is severely impaired in patients with claudication and that, on average, maximum exercise times are ∼40 to 50% of those values observed in healthy controls [1][2][3][4]. These data are based on studies that have excluded individuals with type 2 diabetes, yet a significant number of patients with claudication have type 2 diabetes (see Introduction).…”

Section: Discussionmentioning

confidence: 99%

Effect of type 2 diabetes mellitus on exercise intolerance and the physiological responses to exercise in peripheral arterial disease

2007

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Aims/hypothesis There are conflicting data about the effect of type 2 diabetes mellitus on exercise tolerance in peripheral arterial disease. To elucidate this problem, we compared the tolerance and physiological responses to treadmill and cycle exercise in 31 patients with peripheral arterial disease and intermittent claudication. Materials and methods One group of these patients had type 2 diabetes (n=12) and its members were matched for sex and age with a group of patients who did not have diabetes (n=12). Since BMI and body weight were greater in the diabetic group (28.4±3.7 vs 25.2±2.4 kg/m 2 ; 84.0± 14.6 vs 73.8±8.0 kg), we also studied a third, 'heavy' group of non-diabetic patients with claudication of similar age (n=7; BMI = 30.9±5.3 kg/m 2 ; body weight = 85.2± 8.2 kg). Results Compared with the 'light' non-diabetic group, maximum treadmill times were shorter for the diabetic and heavy non-diabetic groups (1,448 vs 845 and 915 s; ANOVA p=0.01); maximum cycle time also tended to be shorter (ANOVA, p=0.08) in the diabetic and heavy nondiabetic groups (median = 1,231 vs 730 and 797 s). The majority of physiological responses assessed were not different between the groups, although the time constant of oxygen uptake during submaximal treadmill and cycle exercise was significantly larger (ANOVA p<0.05) for the diabetic group. Conclusions/interpretation These data demonstrate that exercise tolerance is lower in diabetic than non-diabetic patients with claudication, but that this difference is due to obesity rather than diabetes itself.

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“…walking performance) by claudicants is $ 50% or less than that observed in healthy controls. 10,32,37,51 Within a group of claudicants there is a large range of performances on a graded treadmill test, where the upper limit can overlap with the lower limit of healthy controls (Figure 2; x axis 10 ). Many factors could contribute to this large variation in walking performance amongst claudicants, 52 including aerobic and mitochondrial metabolism.…”

Section: Walking Performance and Metabolismmentioning

confidence: 99%

Skeletal muscle metabolic changes in peripheral arterial disease contribute to exercise intolerance: a point-counterpoint discussion

2004

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Patients with claudication have a marked impairment in exercise performance. Several factors contribute to this limitation, including reductions in large vessel blood flow and oxygen delivery as well as metabolic abnormalities in skeletal muscle. The relative contribution of these factors and their role in the pathophysiology of the exercise limitation is discussed using a point-counterpoint approach. Future directions for research conclude the discussion.

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Skeletal muscle mitochondrial ATP production rate and walking performance in peripheral arterial disease

Cited by 49 publications

References 34 publications

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

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

Effect of type 2 diabetes mellitus on exercise intolerance and the physiological responses to exercise in peripheral arterial disease

Skeletal muscle metabolic changes in peripheral arterial disease contribute to exercise intolerance: a point-counterpoint discussion

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