Myosin heavy-chain isoform distribution, fibre-type composition and fibre size in skeletal muscle of patients on haemodialysis

Abstract

Chronic uraemia is associated with abnormalities in skeletal muscles, which can affect their working capacity. It is also well known that the fibre-type composition of skeletal muscles influences endurance, muscle strength and power. In this study we therefore determined the size and distribution of muscle fibres and the myosin heavy-chain (MHC) isoform composition in patients on haemodialysis (HD) in order to establish any differences with values for untrained control subjects. Muscle biopsies were obtained from the vastus lateralis muscle of 14 non-diabetic patients on HD. The size and distribution of muscle fibres were evaluated using adenosine triphosphate synthase (ATPase) histochemistry, whilst MHC isoform composition was determined in muscle homogenates using sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Values were compared to those for a group of age-, gender- and BMI-matched untrained control subjects. The aerobic work capacity of the patients was also determined. The MHC composition for I, IIA and IIX isoforms was found to be 35.3% +/- 18.2%, 35.9% +/- 7.1% and 28.9% +/- 15.6%, respectively, findings supported by the ATPase histochemically determined fibre-type composition of the vastus lateralis muscle. The mean fibre area of type 1 and 2 fibres was 3283 +/- 873 and 3594 +/- 1483 MICROm2, respectively. The MHC composition and the size of the type 1 fibres of the patients on HD were significantly different from those of the control subjects. The data demonstrate relatively fewer type 1 and consequently more type 2x fibres, with a corresponding change in MHC isoforms (MHC I and MHC IIX) in the skeletal muscle of patients on HD. Several patients on HD were found to have <15% type 1 (or relative percentage of MHC I) fibres. Such a low percentage of type 1 fibres is very rarely observed in normal untrained subjects. Chronic uraemia more severely affects the composition than the size of fibres.