title: [Cellular mechanisms of pulmonary vasoconstriction in an experimental model of protamine reversal of heparin].
abstract: The neutralisation of heparin by protamine can cause life-threatening pulmonary hypertension. We studied this reaction in animal experimental models (sheep and rat) to determine the cellular mechanisms of the pulmonary vasoconstriction. The heparin-protamine reaction (H-P) with pulmonary hypertension (peak of mean pulmonary artery pressure = 57.3 +/- 2.2 mmHg), decreased cardiac output (-20%), leukopenia (-30%) and plasma release of high concentrations of thromboxane B2 (6.03 +/- 0.03 ng/ml) was constantly observed in sheep. The reaction was identical in sheep with induced thrombocytopenia by administration of antiplatelet antibodies. On the other hand, the neutralisation of heparin by protamine in rats did not cause thromboxane release or pulmonary vasoconstriction although the leukopenia was identical to that observed in sheep. Therefore, the platelets and white blood cells did not seem to cause the pulmonary vasoconstriction induced by the H-P complexes. The inter-species difference observed suggests that pulmonary intravascular macrophages may be responsible for the liberation of eicosanoids and acute pulmonary vasoconstriction occurring during the neutralisation of heparin by protamine.
authors.affiliation: Service de cardiologie, hôpital de la Salpétrière, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Montalescot
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006494:Heparin Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology; D007958:Leukocyte Count; D008264:Macrophages / Q000502:physiology; D011479:Protamines / Q000494:pharmacology*; D011651:Pulmonary Artery; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep; D013929:Thromboxane B2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D006494:Heparin Antagonists; D011479:Protamines; D013929:Thromboxane B2
vernacular_title: Mécanismes cellulaires de la vasoconstriction pulmonaire dans le modèle expérimental de neutralisation de l'héparine par la protamine.