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.
Subject(s)
Cholestasis, Extrahepatic/physiopathology , Manometry , Tight Junctions/physiology , Animals , Bile Ducts/metabolism , Bile Ducts/physiopathology , Biological Transport/physiology , Carbon Radioisotopes , Cell Polarity/physiology , Cholestasis, Extrahepatic/metabolism , Contrast Media/pharmacokinetics , Disease Models, Animal , Elasticity , Epithelial Cells/cytology , Extracellular Space/metabolism , In Vitro Techniques , Infusion Pumps , Lanthanum/pharmacokinetics , Ligation , Male , Mice , Mice, Inbred Strains , Microscopy, Electron , Pressure , Sucrose/pharmacokinetics , Tight Junctions/ultrastructure , Vena Cava, Inferior/physiopathology , ViscosityABSTRACT
Water proton nuclear magnetic resonance relaxation times and magnetization transfer (MT) parameters of rat hearts were studied 24 h or 4 weeks after ligation of the left coronary artery or sham operation. Compared with sham-operated controls, measured relaxation times (T1sat and T2) of both acute and chronic myocardial infarction increased. The MT effect significantly decreased in the infarcted myocardium. The changes in relaxation times and MT effect were significantly greater in chronic infarcts compared with acute infarcts. Improvements in calculated image contrast between normal and infarcted tissue were supported by images of ex vivo hearts with chronic infarction. Image contrast was increased at short echo times in the presence of macromolecular proton pool irradiation. Exploiting changes in tissue MT following myocardial infarction to enhance contrast between normal and infarcted tissue should allow improved identification and characterization of infarcted myocardium.