Chronic changes in skeletal muscle histology and function in peripheral arterial disease.

Abstract

BACKGROUND Peripheral arterial disease (PAD) is associated with an impairment in exercise performance and muscle function that is not fully explained by the reduced leg blood flow during exercise. This study characterized the effects of PAD on muscle function, histology, and metabolism. METHODS AND RESULTS Twenty-six patients with PAD and six age-matched control subjects were studied. Ten of the PAD patients had unilateral disease, which permitted paired comparisons between their diseased and nonsymptomatic legs. All PAD patients had a lower peak treadmill walking time and peak oxygen consumption than controls. Vascular disease (diseased leg in unilateral patients and the most severely diseased leg in bilateral patients) was associated with decreased calf muscle strength compared with control values. In patients with unilateral disease, the diseased legs had a greater percentage of angular fibers (indicating chronic denervation) and a decreased type II fiber cross-sectional area (expressed as percent of total fiber area) compared with the nonsymptomatic, or control, legs. In diseased legs, gastrocnemius muscle strength was correlated with the total calf cross-sectional area (r = 0.78, p < 0.05) and type II fiber cross-sectional area (r = 0.63, p < 0.05). Activities of citrate synthase, phosphofructokinase, and lactate dehydrogenase in all 26 PAD patients (most diseased leg) did not differ from control values. Despite a wide range in citrate synthase activity in PAD patients, activity of this enzyme was not correlated with muscle strength or treadmill exercise performance. CONCLUSIONS In patients with PAD, gastrocnemius muscle weakness is associated with muscle fiber denervation and a decreased type II fiber cross-sectional area. In contrast, the PAD patients displayed substantial heterogeneity in muscle enzyme activities that was not associated with exercise performance. Denervation and type II fiber atrophy may contribute to the muscle dysfunction in patients with PAD and further confirm that the pathophysiology of chronic PAD extends beyond arterial obstruction.

Isokinetic Strength and Endurance in Proximal and Distal Muscles in Patients With Peripheral Artery Disease

“…The reduced endurance in the distal muscle groups in PAD patients has been well described 13,22 and might reflect mitochondrial impairment 27 and the failure of the arterial system to maintain adequate blood flow and consequent oxygen delivery to distal regions of the arterial obstruction during a muscle contraction, which maintains the aerobic nature of the activity. In the present study, 80% of patients presented with distal obstructions (femoropopliteal or popliteal-tibial).…”

“…In the present study, the PAD patients presented a >20% decrease in muscle strength in the distal muscles compared with control subjects. Regensteiner et al 22 compared the PT in plantar flexion and dorsiflexion movements among PAD patients and age-matched control subjects, reporting strength deficits of >20%. These results are also in agreement with other studies, 13,23 and these deficits are mainly caused by neuromuscular dysfunctions, such as denervation, nerve impairment, apoptosis, and muscle atrophy, which have been adequately described in the distal muscles of PAD patients.…”

Atherosclerotic Vascular Disease Conference

“…88,89 In patients with claudication, muscle injury from ischemia-reperfusion during walking and rest causes partial denervation of limb muscles and alterations of muscle fiber distributions that can reduce muscle function additionally. 90,91 Skeletal muscle metabolism is also altered with accumulation of acylcarnitines (markers of abnormal muscle metabolism) …”

Avaliação da reprodutibilidade de testes funcionais na doença arterial periférica

“…Os portadores de DAP sintomáticos possuem passo encurtado, cadência lenta e deficit no equilíbrio, motivando a redução do desempenho, da velocidade de caminhar e da capacidade de percorrer longas distâncias 2,[5][6][7][8][9][10][11][12] . Pacientes com DAP grave caminham com velocidades reduzidas para conseguir percorrer maiores distâncias 13 .…”

“…Vários autores demonstraram que os portadores de DAP têm pico de consumo de oxigênio 50% menor do que indivíduos normais, contribuindo para a redução do desempenho durante o exercício e a restrição na capacidade de realizar atividades domiciliares 2,8,12,14 . Os pacientes que apresentam CI têm suas atividades de vida diária reduzidas e baixa qualidade de vida 1,2,6,10 .…”