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Manometric changes during retrograde biliary infusion in mice.

S M Wiener1, R F Hoyt, J R Deleonardis

  • 1Molecular Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. SWiener@Partners.org

American Journal of Physiology. Gastrointestinal and Liver Physiology
|July 18, 2000
PubMed
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Retrograde biliary infusion increases pressure, causing tight junctions to open and allowing substances to leak into tissues. Controlling this pressure may enable targeted delivery of large molecules.

Area of Science:

  • Hepatology
  • Gastroenterology
  • Biliary Physiology

Background:

  • Understanding the physiological effects of retrograde biliary infusion is crucial for developing targeted therapies.
  • Biliary pressure dynamics and their impact on tight junction permeability remain incompletely understood.

Purpose of the Study:

  • To investigate the manometric, ultrastructural, radiographic, and physiological consequences of retrograde biliary infusion in mice.
  • To determine the relationship between intraluminal biliary pressure and paracellular leakage.
  • To assess the impact of cholestasis on pressure-induced biliary changes.

Main Methods:

  • Retrograde biliary infusion in normostatic and cholestatic mice.
  • Manometric measurements of intraluminal biliary pressure.

Related Experiment Videos

  • Ultrastructural analysis of tight junctions using lanthanum chloride.
  • Radiographic tracking of infused radiopaque dye and radiolabeled sucrose.

    • Main Results:

    • Infusion volume, rate, and viscosity directly influenced intraluminal biliary pressure.
    • Elevated pressures led to pressure-dependent opening of tight junctions and paracellular leakage.
    • Chronic bile duct obstruction reduced peak pressures and leakage levels.
    • Infused substances rapidly redistributed systemically via hepatic venous drainage.

    Conclusions:

    • Elevated intraluminal biliary pressure acutely opens tight junctions, facilitating substance movement into tissues.
    • Cholestasis alters the pressure-induced leakage response.
    • Controlling intraluminal pressure offers potential for selective delivery of macromolecules to specific tissue compartments.