Search

The relationship between microvascular damage and the presence of muscle fibre atrophy and necrosis has been investigated in skeletal muscle biopsies taken from 57 patients with multiple organ failure. Immunohistochemical studies showed no loss of capillaries and no luminal thrombosis, while neutrophil leucocytes were more prevalent in the patients' biopsies than in controls. Deposition of the complement membrane attack complex (C5-9MAC) in capillaries was observed in 41% of cases. Endothelial activation was suggested by an increased intensity of expression of ICAM-1, and by an increased proportion of capillaries expressing P selectin and E selectin, although this was not directly associated with neutrophil accumulation. Endothelial swelling was present in many biopsies with 38% of the biopsies having larger capillary profiles on immunohistochemical labelling for von Willebrand factor (vWF), thrombomodulin and CD34, and on Ulex europaeus agglutinin 1 binding. Endothelial swelling was confirmed by image analysis and morphometric evaluation of capillary ultrastructure, however, the capillary luminal area was not reduced as the capillaries were dilated. Increased vWF labelling was associated with C5-9MAC deposition and with fibre necrosis, but the vascular changes were not related to fibre atrophy nor to clinical indices of the severity of the patients' illness. The results suggest that microvascular damage and ischaemia may not be major factors in the pathogenesis of muscle fibre damage in multiple organ failure, but that endothelial activation is a common occurrence. The variability in the patterns of markers of endothelial activation, and the small proportion of capillaries affected, may reflect the complexity of the endothelial response to circulating or locally produced cytokines.

A 56-year-old female and her 34-year-old daughter presented with a predominantly distal myopathy affecting the peroneal and calf muscles, neck flexors and hand muscles. Both patients and two other daughters had cardiac arrhythmias, three requiring the insertion of cardiac pacemakers. Skeletal muscle biopsies revealed a complex myopathic process with granular degeneration, rimmed vacuoles and eosinophilic cytoplasmic inclusions. Ultrastructurally, the inclusions were composed of electron dense granular material and filaments forming linear masses beneath the sarcolemma and rounded masses within the cytoplasm of the fibres. Immunohistochemistry revealed labelling of the inclusions for desmin, dystrophin and vimentin, but not for alpha-actinin, spectrin, utrophin or myosin heavy chains. This family shows a hereditary distal myopathy with some features in common with previously-reported cases in which biopsies showed cytoplasmic inclusion bodies containing desmin. This group of diseases is clinically and pathologically heterogeneous. In the present cases, the accumulation of cytoplasmic filaments may reflect a generalised disturbance of filamentous protein metabolism rather than a specific disorder of desmin.

The lectin Dolichos biflorus agglutinin has been used to identify mast cells in normal skeletal muscle and to investigate changes in their number in a wide range of human neuromuscular diseases and in rat muscle damaged by the local anaesthetic bupivacaine. Few mast cells were found in the perimysium of normal skeletal muscle but numbers were increased in human muscle biopsies which showed necrosis and regeneration of fibrosis. In bupivacaine-induced muscle damage, increased mast cell counts occurred during the necrotic phase and particularly during the phase of active regeneration. In addition, increased numbers of mast cells were observed in the underlying histologically normal muscle. These results show that mast cells are influenced by pathological changes in skeletal muscle and, in view of the known functions of mast cells in other tissues, it is possible that they are capable of modulating disease processes in muscle.