AN IN-VITRO METHOD FOR ASSESSING THE EFFECTS OF PRO-INFLAMMATORY AND ANTIINFLAMMATORY COMPOUNDS ON MICROVASCULAR PERMEABILITY IN THE RAT SMALL-INTESTINE

A method is described in which the blood vessels of the rat mesentery and small intestine were perfused for 15 min in vitro with a gelatin-c ontaining physiological salt solution. Colloidal carbon (CC) was then added to the perfusate. In control preparations, very little CC was tr apped in the microvessels of the small intestine, but if platelet-acti vating factor (PAF) was added for 5 min before the infusion of CC, man y microvessels were ''blackened.'' When the PAF antagonist BN52021 was included in the perfusate throughout, the ''blackening'' response to PAF was significantly reduced. Using micrographs of fixed specimens of gut, the amounts of ''blackening'' in the microvessels of the villi, the crypts of Lieberkuhn, and the muscularis were assessed using semia utomated image analysis. The technique provides a means of investigati ng the effects on microvascular permeability of pro-inflammatory and a nti-inflammatory compounds. It is particularly useful for testing subs tances which, because of their highly toxic nature, cannot be administ ered systemically in vivo.