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

Oliver Baum, Eleonora Torchetti, Corinna Malik, Birgitte Hoier, Meegan Walker, Philip J Walker, Adolfo Odriozola, Franziska Graber, Stefan A Tschanz, Jens Bangsbo, Hans Hoppeler, Christopher D Askew, Ylva Hellsten

Intermittent claudication (IC) is the most commonly reported symptom of peripheral arterial disease (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 knee-extension protocol. Capillary density was lower (411±90 mm(-2)versus 506±95 mm(-2); P≤0.05) in the biopsies of the IC patients than in those of the controls. The basement membrane (BM) around capillaries was thicker (543±82 nm versus 423±97 nm; P≤0.01) and the volume density of mitochondria was lower (3.51±0.56% versus 4.60±0.74; P≤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±9.9 W versus 33.5±9.4 W; P≤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.