Acute pulmonary vasoconstriction and thromboxane release during protamine reversal of heparin anticoagulation in awake sheep. Evidence for the role of reactive oxygen metabolites following nonimmunological complement activation. 1988

D R Morel, and E Lowenstein, and T Nguyenduy, and D R Robinson, and J E Repine, and D E Chenoweth, and W M Zapol
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.

When protamine (2 mg/kg) was injected intravenously into awake sheep 5 minutes after infusing heparin (200 units/kg), there was transient diffuse pulmonary vasoconstriction with mean pulmonary arterial pressure increasing from 18.0 +/- 0.7 to 43.8 +/- 2.7 mm Hg at 1 minute (x +/- SEM; n = 10). In addition, there was profound leukopenia (36.9 +/- 7.7% of baseline values at 2 minutes) with transpulmonary leukocyte sequestration and transiently elevated plasma concentrations of C3a (from 420 +/- 146 to 1,599 +/- 249 ng/ml; n = 3, p less than 0.01) and thromboxane B2 (from 0.30 +/- 0.05 to 6.3 +/- 2.8 ng/ml; n = 10, p less than 0.0001), without significant increases of plasma 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, leukotrienes, or histamine. Intravenous injection of protamine alone produced no hemodynamic effects and did not increase plasma levels of vasoconstrictor eicosanoids. Intravenous pretreatment with either a cyclooxygenase inhibitor or a hydrogen peroxide scavenger (dimethylthiourea) blocked both the increases of thromboxane levels and the pulmonary vasoconstriction.

UI MeSH Term Description Entries
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D011479 Protamines A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692) Protamine,Protamine Sulfate,Protamine Chloride,Chloride, Protamine,Sulfate, Protamine
D003167 Complement Activation The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES. Activation, Complement,Activations, Complement,Complement Activations
D004121 Dimethyl Sulfoxide A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. DMSO,Dimethyl Sulphoxide,Dimethylsulfoxide,Dimethylsulphinyl,Dimethylsulphoxide,Dimexide,Rheumabene,Rimso,Rimso 100,Rimso-50,Sclerosol,Sulfinylbis(methane),Rimso 50,Rimso50,Sulfoxide, Dimethyl,Sulphoxide, Dimethyl
D006493 Heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001158 Arteries The vessels carrying blood away from the heart. Artery
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli
D013890 Thiourea A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.

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