Manometric changes during retrograde biliary infusion in mice

The manometric, ultrastructural, radiographic, and physiological consequenc es of retrograde biliary infusion were determined in normostatic and choles tatic 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 change s observed was consistent with biliary ductular and/or canalicular filling followed by leakage at a threshold pressure. Retrograde infusion with signi ficant elevations in pressure led to paracellular leakage of lanthanum chlo ride, radiopaque dye, and [C-14] sucrose with rapid systemic redistribution via sinusoidal and subsequent hepatic venous drainage. Chronic extrahepati c bile duct obstruction resulted in significantly smaller peak intrabiliary pressures and lower levels of paracellular leakage. These findings indicat e that under both normostatic and cholestatic conditions elevated intrabili ary volumes/pressures result in an acute pressure-dependent physical openin g of tight junctions, permitting the movement of infusate from the intrabil iary space into the subepithelial tissue compartment. Control of intralumin al pressure may potentially permit the selective delivery of macromolecules >18-20 Angstrom in diameter to specific histological compartments.