Increased sheep lung vascular permeability caused by histamine.
To see whether histamine increases lung vascular permeability to protein, we compared the effects of steady-state histamine infusions on lung vascular pressures, lung lymph flow, and lung lymph protein content with the effects of mechanically elevated lung vascular pressures on these variables in the same unanesthetized sheep. We surgically implanted catheters in the pulmonary artery, the left atrium, the superior vena cava, and a main lung lymphatic. After the sheep had recovered from surgery, we carried out steady-state experiments without anesthesia. Histamine induced a dose-related, quickly reversible increase in lung lymph flow without affecting pulmonary artery pressure, and it caused left atrial pressure to fall. During 4-hour intravenous 4-mug/kg min-1 histamine infusions, lymph flow and lymph protein clearance (lymph flow X lymph-plasma protein concentration ratio) increased more than they did with mechanically elevated pressure even though vascular pressures fell. Lymph-plasma protein ratios decreased linearly with increasing lymph flow during increased pressure experiments, but during histamine infusions the ratios did not decrease even though lymph flow increased 2-6-fold. Lymph clearance and permeability-surface area products (PS) for eight protein fractions with molecular radii ranging from 36 to 100 A decreased with increasing molecular size in base-line, increased pressure, and histamine studies. PS values for all eight fractions were significantly higher than base line in histamine experiments but not in increased pressure experiments. Four-hour intravenous histamine infusions caused moderate increases in lung water content. Left atrial infusions had less effect on lymph flow than did intravenous infusions. We conclude that histamine causes pulmonary vascular permeability to protein to increase but that the effects on exchanging vessel porosity are more modest than those suggested for systemic microvessels. Histamine should be considered a possible mediator of increased lung vascular permeability.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D002199:Capillary Permeability; D004305:Dose-Response Relationship, Drug; D005260:Female; D006325:Heart Atria; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008168:Lung / Q000098:blood supply*; D008196:Lymph / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism; D012756:Sheep
D001798:Blood Proteins; D011506:Proteins; D006632:Histamine