Circulation, Vol 87, 413-421, Copyright © 1993 by American Heart Association
JG Regensteiner, EE Wolfel, EP Brass, MR Carry, SP Ringel, ME Hargarten, ER Stamm and WR Hiatt
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.
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Chronic changes in skeletal muscle histology and function in peripheral arterial disease
Department of Medicine, University of Colorado School of Medicine, Denver.
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