Serum but not plasma produces injury in the perfused rabbit lung.
Serum contains proteins that may produce lung injury directly by affecting endothelial cells and indirectly by modulating the effects of endotoxin (lipopolysaccharide). We studied the effects of 10% serum, 10% plasma, and 10% plasma plus 2 micrograms/mL lipopolysaccharide on pulmonary hypertension and vascular permeability in the isolated perfused rabbit lung. Control lungs perfused with Krebs-Henseleit buffer containing 3% albumin for 2 h had stable pulmonary vascular pressures and permeability (measured by the capillary filtration coefficient). Serum produced pulmonary hypertension and increased pulmonary vascular permeability. In contrast, plasma, with and without lipopolysaccharide, did not alter pulmonary vascular pressures or permeability. Pretreatment with the cyclooxygenase inhibitor indomethacin prior to the addition of serum prevented the serum-induced increase in pulmonary vascular pressures and permeability. We conclude that the deleterious effects of serum are not due to plasma proteins per se, but instead are related to activation of the coagulation cascade during preparation of the serum. The deleterious effects of serum appear to be mediated by cyclooxygenase metabolites of arachidonic acid. Finally, endotoxin, even with the addition of plasma, does not directly produce lung injury.
Mouchawar
A M
AM
Department of Anesthesia, Stanford University Medical Center, CA 94305-5117.
Kavanagh
B P
BP
Pearl
R G
RG
D000818:Animals; D001769:Blood / Q000276:immunology; D001790:Blood Physiological Phenomena; D001794:Blood Pressure; D001798:Blood Proteins / Q000009:adverse effects*; D002199:Capillary Permeability / Q000502:physiology; D003167:Complement Activation; D004926:Escherichia coli; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010477:Perfusion; D010949:Plasma / Q000502:physiology*; D011651:Pulmonary Artery; D011817:Rabbits
D001798:Blood Proteins; D008070:Lipopolysaccharides; D007213:Indomethacin