title: Involvement of fibrinogen in protamine-induced pulmonary hypertension.
abstract: Protamine reversal of heparin anticoagulation occasionally results in pulmonary hypertension as well as systemic hypotension. To examine the contribution of blood components to this induction of pulmonary hypertension, we developed an isolated rat lung perfusion model and perfused heparinized plasma, heparinized serum, and Hepes (4% bovine serum albumin, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, 5 mM glucose, in warm physiological saline) buffer solution with or without fibrinogen. Perfusion with heparinized plasma and Hepes buffer solution with fibrinogen caused pulmonary hypertension; perfusion with heparinized serum or Hepes buffer solution without fibrinogen did not, suggesting that fibrinogen is involved in the induction of pulmonary hypertension. We also labeled protamine with 125I and compared the amounts of protamine accumulating in the lung with different concentrations of fibrinogen. The amount of protamine trapped in the lung increased according to the concentration of fibrinogen. Fibrinogen may accelerate the reaction between pulmonary endothelial cells and protamine or protamine-heparin complexes. In the mechanism of protamine-induced pulmonary hypertension, fibrinogen, as well as heparin and protamine, may be an essential component.
authors.affiliation: Institute for Biomedical Engineering, University of Utah, 803 North 300 West, Salt Lake City, Utah 84103, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sogawa
authors.forename: S F
authors.initials: SF
authors.lastname: Mohammad
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001769:Blood; D001794:Blood Pressure; D002417:Cattle; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000008:administration & dosage / Q000502:physiology*; D006493:Heparin / Q000008:administration & dosage; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D010477:Perfusion; D011479:Protamines / Q000008:administration & dosage; D011651:Pulmonary Artery / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016861:Cyclooxygenase Inhibitors; D011479:Protamines; D005340:Fibrinogen; D006493:Heparin; D001241:Aspirin