MICROVASCULAR PERMEABILITY IN ISOLATED VASCULARLY PERFUSED SMALL-INTESTINE OF RATS

Intestinal microvascular permeability was studied in the isolated vascularly perfused small intestine of the rat by arterial injection of tracer molecules and collection of venous samples. The injection mixture contained a rhodamine-labeled dextran and a fluorescein-labeled dextran 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 model (PTM) was used to assess vasopermeability. The results indicate that the experimental system cannot be considered a pure WSM or a PTM. No different intrinsic clearance (Cl-int,Cl-i) values were found by applying 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 histamine (10(-5)-10(-3) M) and destruction of the endothelium via perfusion with distilled water increased the permeability for the tracers. We have established a technique for measurement of microvascular permeability characteristics in the rat small intestine. Histamine-induced changes and destruction of the endothelium can be detected in a quantitatively reliable way.