Anatomic pathway of fluid leakage in fluid-overload pulmonary edema in mice

Mice were given an intravenous injection of isotonic saline containing horseradish peroxidase (HRP) as an ultrastructural marker in an attempt to determine the site of fluid leakage from the vascular space to the air space in the lung. The localization of HRP was studied by ultrastructural histochemistry. When injected in a small volume of saline (0.1 ml), HRP was confined in the vascular space. When the volume of saline was increased to 1.0 ml, the reaction product of HRP was found first in the intercellular junctions of the arterial endothelium and then through the arterial wall. The reaction product was traced from the arterial wall to the peribronchiolar tissue, bronchiolar wall, and the intercellular space of the bronchiolar epithelium. HRP was seen in direct contact with the air space in the bronchiole. It is suggested that in fluid-overload pulmonary edema, fluid leaks through the arterial wall to the peribronchiolar tissue and then into the intercellular space of the bronchiolar epithelium. Alveolar is probably a result of the backflow of fluid from the bronchiole.