BLOOD COAGULATION & FIBRINOLYSIS, cilt.21, ss.339-348, 2010 (SCI İndekslerine Giren Dergi)
Sepsis/endotoxemia causes platelet dysfunctions, abnormalities in coagulation and hemostatic mechanisms leading to organ dysfunctions and mortality. Choline prevents organ injury and improves survival during endotoxemia. The main objective of the present study was to determine the effects of choline or cytidine-5'-diphosphocholine (CDP-choline) on endotoxin-induced activation of coagulation and development of disseminated intravascular coagulation (DIC). Dogs were treated intravenously (i.v.) with saline, choline (20 mg/kg), or CDP-choline (70 mg/kg) three times with 4-h intervals starting 5 min before i.v. injection of endotoxin (1 mg/kg). Platelet counts and functions, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, coagulation factors, D-dimer and antithrombin (AT) were measured before and at 0.5-96 h after endotoxin. Circulating platelet, fibrinogen, coagulation factors and AT were decreased, whereas PT and aPTT were prolonged and serum D-dimer levels were elevated after endotoxin. Endotoxin-induced reductions in platelet counts and functions, fibrinogen, coagulation factors and AT were attenuated or blocked by choline or CDP-choline. Choline or CDP-choline blocked endotoxin-induced prolongation in PT and aPTT and enhancement in D-dimer. Elevated DIC scores were attenuated by choline and blocked by CDP-choline. Choline administration increased serum choline concentrations and caused bradycardia. Choline also increased choline and acetylcholine contents of circulating mononuclear cells and inhibited radioligand binding to their cholinergic receptors. These data show that choline administration, as choline chloride or CDP-choline, restores the abnormalities in the primary, secondary, and tertiary hemostasis and prevents the development of DIC during experimental endotoxemia in dogs probably by increasing both neuronal and nonneuronal cholinergic activity. Blood Coagul Fibrinolysis 21:339-348 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.