title: Capillary ultrastructure and mitochondrial volume density in skeletal muscle in relation to reduced exercise capacity of patients with intermittent claudication.
abstract: 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) vs. 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 vs. 423 ± 97 nm; P ≤ 0.01) and the volume density of mitochondria was lower (3.51 ± 0.56% vs. 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 vs. 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.
authors.affiliation: Institute of Physiology, CharitéCrossOver (CCO), Berlin, Germany; Institute of Anatomy, University of Bern, Switzerland; oliver.baum@charite.de.
authors.forename: Oliver
authors.identifier: 0000-0001-8076-8789
authors.initials: O
authors.lastname: Baum
authors.affiliation: Institute of Anatomy, University of Bern, Switzerland;
authors.forename: Eleonora
authors.initials: E
authors.lastname: Torchetti
authors.affiliation: Institute of Anatomy, University of Bern, Switzerland;
authors.forename: Corinna
authors.initials: C
authors.lastname: Malik
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark;
authors.forename: Birgitte
authors.initials: B
authors.lastname: Hoier
authors.affiliation: School of Health and Sport Sciences, University of the Sunshine Coast, Australia;
authors.forename: Meegan
authors.initials: M
authors.lastname: Walker
authors.affiliation: Discipline of Surgery, School of Medicine and Centre for Clinical Research, The University of Queensland, Australia; and National Health and Medical Research Council, Centre of Research Excellence for Peripheral Arterial Diseases, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Walker
authors.affiliation: Institute of Anatomy, University of Bern, Switzerland;
authors.forename: Adolfo
authors.initials: A
authors.lastname: Odriozola
authors.affiliation: Institute of Anatomy, University of Bern, Switzerland;
authors.forename: Franziska
authors.initials: F
authors.lastname: Graber
authors.affiliation: Institute of Anatomy, University of Bern, Switzerland;
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Tschanz
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark;
authors.forename: Jens
authors.initials: J
authors.lastname: Bangsbo
authors.affiliation: Institute of Anatomy, University of Bern, Switzerland;
authors.forename: Hans
authors.initials: H
authors.lastname: Hoppeler
authors.affiliation: School of Health and Sport Sciences, University of the Sunshine Coast, Australia; National Health and Medical Research Council, Centre of Research Excellence for Peripheral Arterial Diseases, Australia.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Askew
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark;
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D000368:Aged; D002196:Capillaries / Q000502:physiology*; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology
keywords: capillary; morphometry; peripheral arterial disease; skeletal muscle; transmission electron microscopy