MICROVASCULAR PERMEABILITY IN ISOLATED VASCULARLY PERFUSED SMALL-INTESTINE OF RATS

Intestinal microvascular permeability was studied in the isolated vasc ularly perfused small intestine of the rat by arterial injection of tr acer molecules and collection of venous samples. The injection mixture contained a rhodamine-labeled dextran and a fluorescein-labeled dextr an or free fluorescein. Pharmacokinetic analysis, based on statistical moment theory, of the tracer outflow concentration-time curve and the application of either the well-stirred model (WSM) or parallel tube m odel (PTM) was used to assess vasopermeability. The results indicate t hat the experimental system cannot be considered a pure WSM or a PTM. No different intrinsic clearance (Cl-int,Cl-i) values were found by ap plying the two models: cl(int,i) (in ml/min) = 1.23 +/- 0.14 (radius 0 .5 nm); 0.44 +/- 0.09 (radius 1.4 nm); 0.31 +/- 0.08 (radius 2.2 nm); 0.02 +/- 0.01 (radius 6.0 nm); and 0 (radius 20.8 nm). Infusion of his tamine (10(-5)-10(-3) M) and destruction of the endothelium via perfus ion with distilled water increased the permeability for the tracers. W e have established a technique for measurement of microvascular permea bility characteristics in the rat small intestine. Histamine-induced c hanges and destruction of the endothelium can be detected in a quantit atively reliable way.