Measurement of canine gastric vascular permeability to plasma proteins in the normal and protein-losing states.

An isolated segment of the greater curvature of a dog's stomach was perfused at constant flow through a single cannulated artery with donor blood containing 131I-albumin, 125I-fibrinogen, and papaverine. Perfusion pressure was 30-50 mmHg, and venous pressure was set at 15 mmHg. Venous blood was collected in 1-min samples for 60 min. Filtration of fluid and loss of labeled proteins were calculated as the difference between measured arterial inflow and venous outflow. Permeability-surface area products (PS) were calculated for the proteins, and reflection coefficients (sigma) were calculated from solute flux and filtration. Intraarterial infusion of histamine (1.6-1.9 microgram . ml-1) increased filtration and PS and decreased sigma for albumin but not fibrinogen. When protein-losing was established by topical irrigation with 10 mM dithiothreitol in neutral solution, filtration and PS increased, and sigma for albumin but not fibrinogen decreased. Irrigation of the mucosa with 10 mM salicylic acid in 100 mN HCl caused bleeding that was quantitated by addition of 51Cr-erythrocytes to perfusing blood. Filtration and PS increased, and sigma for albumin but not fibrinogen decreased. Hematocrit of blood lost remained low during extensive mucosal damage. Effects of histamine infusion were attenuated or abolished by cimetidine (4 mg . kg-1 loading, 1.4 mg . kg-1 . h-1 continuous infusion) or by pyrilamine maleate (5 mg . kg-1 bolus injection at beginning of irrigation, repeated at 40-50 min). Pyrilamine attenuated or abolished effects of topical dithiothreitol or salicylic acid. We conclude that during protein loss caused by dithiothreitol or salicylic acid, histamine released within the mucosa causes increased vascular permeability for plasma proteins.