Alterations in the muscle-to-capillary interface in patients with different degrees of chronic obstructive pulmonary disease

Abstract

BackgroundIt is hypothesized that decreased capillarization of limb skeletal muscle is implicated in the decreased exercise tolerance in COPD patients. We have recently demonstrated decreased number of capillaries per muscle fibre (CAF) but no changes in CAF in relation to fibre area (CAFA), which is based on the diffusion distance between the capillary and muscle fibre. The aim of the current study is to investigate the muscle-to-capillary interface which is an important factor involved in oxygen supply to the muscle that has previously been suggested to be a more sensitive marker for changes in the capillary bed compared to CAF and CAFA.Methods23 COPD patients and 12 age-matched healthy subjects participated in the study. Muscle-to-capillary interface was assessed in muscle biopsies from the tibialis anterior muscle using the following parameters:1) The capillary-to-fibre ratio (C:Fi) which is defined as the sum of the fractional contributions of all capillary contacts around the fibre2) The ratio between C:Fi and the fibre perimeter (CFPE-index)3) The ratio between length of capillary and fibre perimeter (LC/PF) which is also referred to as the index of tortuosity.Exercise capacity was determined using the 6-min walking test.ResultsA positive correlation was found between CFPE-index and ascending disease severity with CFPE-index for type I fibres being significantly lower in patients with moderate and severe COPD. Furthermore, a positive correlation was observed between exercise capacity and CFPE-index for both type I and type IIa fibres.ConclusionIt can be concluded that the muscle-to-capillary interface is disturbed in the tibialis anterior muscle in patients with COPD and that interface is strongly correlated to increased disease severity and to decreased exercise capacity in this patient group.

Blunted muscle angiogenic training-response in COPD patientsversussedentary controls

“…In agreement with previous works, the baseline level of muscle capillarisation was lower in COPD patients [4,7] and well correlated with muscle dysfunction and O 2 consumption before training [4]. We observed an increase in the capillaryto-fibre ratio, which may indicate a training-induced improvement in the capacity to transfer O 2 to myofibres in both COPD patients and SHS.…”

“…Muscle fibre type and mean cross-sectional area (CSA) were assessed after immunohistochemistry on frozen sections (10-mm thickness) from the muscle biopsies, using antibodies specific to each myosin heavy chain isotype (University of Iowa, Iowa City, IO, USA) [4,25]. Capillaries were visualised by immunochemistry with the monoclonal antibody against CD31 (#550389; BD Biosciences, Franklin Lakes, NJ, USA).…”

“…In chronic obstructive pulmonary disease (COPD), the skeletal muscle dysfunction affects the patient's prognosis, exercise tolerance and health-related quality of life [2]. This muscle impairment is characterised by cellular changes, with decreases in the proportion of type I oxidative fibres, oxidative enzymes [3] and capillaries [4]. In particular, the alteration in the capillary supply [4] is well correlated with the impaired muscle function and aerobic exercise capacity of these patients.…”

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

“…The capillary to muscle fiber cross-sectional area is similar in subjects with COPD and healthy subjects (174). This may indicate that the oxygen diffusion distance is maintained in COPD (174).…”

“…This is not a universal finding (172), perhaps due to the fact that, in some studies, patients were involved in exercise training, which could improve muscle capillarization (163,173). The capillary to muscle fiber cross-sectional area is similar in subjects with COPD and healthy subjects (174). This may indicate that the oxygen diffusion distance is maintained in COPD (174).…”