Modulation of microvascular permeability by 21-aminosteroids after burn injuries

Burn injuries initiate lipid peroxidation in capillary endothelial cells an d cause alterations in microvascular permeability with subsequent leakage o f fluid and protein from the plasma into the interstitium. We evaluated the effects of two lazaroid compounds (U74389F and U75412E) on alterations in microvascular permeability that resulted from burn injuries. A canine model was used for the evaluation of microvascular permeability at the site of t he burn injury with the use of a measure of the reflection coefficient (sig ma(d)) Hindpaw lymph flow, lymph and plasma total protein contentrations, a nd arterial, venous, and capillary pressures were measured before burn inju ries and for 6 hours in 6 different groups. Footpaw weight gain was then ca lculated as the percentage of increase of experimental hindpaw relative to the contralateral paw. The damage was attenuated by 20 mg/kg of lazaroid U7 5412E given before the injuries, but a lower dose was not effective. This a gent was also effective in limiting edema formation, as evidenced by change s in footpaw weight gain. However, the administration of either lazaroid co mpound produced no significant effect on the burn-induced changes in capill ary permeability. We conclude that these lazaroids do not prevent burn-indu ced changes in permeabilitv at the site of injury when administered after a n injury U75412E administered before the injury was effective in limiting t he alterations in microvascular permeability.