title: Manometric changes during retrograde biliary infusion in mice.
abstract: The manometric, ultrastructural, radiographic, and physiological consequences of retrograde biliary infusion were determined in normostatic and cholestatic mice. Intraluminal biliary pressure changed as a function of infusion volume, rate, and viscosity. Higher rates of constant infusion resulted in higher peak intraluminal biliary pressures. The pattern of pressure changes observed was consistent with biliary ductular and/or canalicular filling followed by leakage at a threshold pressure. Retrograde infusion with significant elevations in pressure led to paracellular leakage of lanthanum chloride, radiopaque dye, and [(14)C]sucrose with rapid systemic redistribution via sinusoidal and subsequent hepatic venous drainage. Chronic extrahepatic bile duct obstruction resulted in significantly smaller peak intrabiliary pressures and lower levels of paracellular leakage. These findings indicate that under both normostatic and cholestatic conditions elevated intrabiliary volumes/pressures result in an acute pressure-dependent physical opening of tight junctions, permitting the movement of infusate from the intrabiliary space into the subepithelial tissue compartment. Control of intraluminal pressure may potentially permit the selective delivery of macromolecules >18-20 A in diameter to specific histological compartments.
authors.affiliation: Molecular Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. SWiener@Partners.org
authors.forename: S M
authors.initials: SM
authors.lastname: Wiener
authors.forename: R F
authors.initials: RF
authors.lastname: Hoyt
authors.forename: J R
authors.initials: JR
authors.lastname: Deleonardis
authors.forename: R R
authors.initials: RR
authors.lastname: Clevenger
authors.forename: K R
authors.initials: KR
authors.lastname: Jeffries
authors.forename: K
authors.initials: K
authors.lastname: Nagashima
authors.forename: M
authors.initials: M
authors.lastname: Mandel
authors.forename: J
authors.initials: J
authors.lastname: Owens
authors.forename: M
authors.initials: M
authors.lastname: Eckhaus
authors.forename: R J
authors.initials: RJ
authors.lastname: Lutz
authors.forename: B
authors.initials: B
authors.lastname: Safer
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000378:metabolism / Q000503:physiopathology; D001692:Biological Transport / Q000502:physiology; D002250:Carbon Radioisotopes; D016764:Cell Polarity / Q000502:physiology; D001651:Cholestasis, Extrahepatic / Q000378:metabolism / Q000503:physiopathology*; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004548:Elasticity; D004847:Epithelial Cells / Q000166:cytology; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D007260:Infusion Pumps; D007811:Lanthanum / Q000493:pharmacokinetics; D008026:Ligation; D008297:Male; D008365:Manometry; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D011312:Pressure; D013395:Sucrose / Q000493:pharmacokinetics; D019108:Tight Junctions / Q000502:physiology* / Q000648:ultrastructure; D014682:Vena Cava, Inferior / Q000503:physiopathology; D014783:Viscosity
chemical_list: D002250:Carbon Radioisotopes; D003287:Contrast Media; C028521:lanthanum chloride; D013395:Sucrose; D007811:Lanthanum