title: Microvascular permeability in isolated vascularly perfused small intestine of rats.
abstract: 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 (Clint,i) values were found by applying the two models: Clint,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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
authors.forename: A D
authors.initials: AD
authors.lastname: Kraneveld
authors.forename: A S
authors.initials: AS
authors.lastname: Koster
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007201:Indicator Dilution Techniques; D007421:Intestine, Small / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008954:Models, Biological; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012235:Rhodamines
chemical_list: D003911:Dextrans; D012235:Rhodamines; C015219:fluorescein isothiocyanate dextran; C051311:rhodamine dextran; D006632:Histamine; D016650:Fluorescein-5-isothiocyanate