An in vitro method for assessing the effects of pro-inflammatory and anti-inflammatory 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-containing physiological salt solution. Colloidal carbon (CC) was then added to the perfusate. In control preparations, very little CC was trapped in the microvessels of the small intestine, but if platelet-activating factor (PAF) was added for 5 min before the infusion of CC, many 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 semiautomated image analysis. The technique provides a means of investigating the effects on microvascular permeability of pro-inflammatory and anti-inflammatory compounds. It is particularly useful for testing substances which, because of their highly toxic nature, cannot be administered systemically in vivo.