The Site of Vascular Response to the α-Toxin of Clostridium Perfringens Type A in Skeletal Muscle

The vascular response to the α-toxin of Clostridium perfringens type A, was observed topographically in the cremaster muscle of the rat, in terms of exudation, labelling of damaged vessels by circulating carbon, and in addition histologically for patency of the vascular plexus.It was confirmed that the permeability response is biphasic. The short-lived immediate phase corresponds to that of venular labelling, and the delayed phase reaches its peak rather later than the corresponding phase of capillary labelling. The intensity and extent of these responses are determined by the degree of injury, but their shape and timing, especially in the immediate phase, vary almost as consistently with the duration of exposure to circulating dye or carbon.After the standard dose of toxin, vascular patency is largely unaffected until 24 hours. Apparently irreversible vascular occlusion occurs rather earlier with larger doses. A three-fold reduction of the standard dose proportionately reduces both exudation and capillary labelling but leaves immediate venular labelling unaffected, suggesting that the latter is not dose dependent and therefore non-specific. Prolongation of moderate venular labelling into the middle of the delayed phase may occur at this dosage. Its absence after the standard dose suggests that delayed inhibition of venular reactivity may be occurring.Irregular labelling of venules and small veins persists throughout the delayed phase with doses 2·4 or more times the standard dose. A brief ultramicroscopic survey revealed appearances in both venules and capillaries at 1-2 hours after injury closely comparable to those which have been described for Cl. oedematiens toxin at 6-24 hours.In rats given carbon during the delayed phase, the effective vascular patency 10 minutes later includes half of the labelled capillaries up to 10 μm in diameter. This proportion is little affected by toxin dose, but intensely so when the carbon clearance time is increased, suggesting that such injured microvessels may be a major source of plasma protein exudation.