Choline treatment effects on blood clotting in dogs with endotoxin

Abstract

Sepsis/endotoxemia associates with coagulation abnormalities. We showed previously that exogenous choline treatment reversed the changes in platelet count and function as well as prevented disseminated intravascular coagulation (DIC) in endotoxemic dogs. The aim of this follow-up study was to evaluate the effect of treatment with choline or cytidine-5'-diphosphocholine (CDP-choline), a choline donor, on endotoxin-induced hemostatic alterations using thromboelastography (TEG). Dogs were randomized to six groups and received intravenously (iv) saline, choline (20&#xa0;mg/kg) or CDP-choline (70&#xa0;mg/kg) in the control groups, whereas endotoxin (0.1&#xa0;mg/kg, iv) was used alone or in combination with choline or CDP-choline at the same doses in the treatment groups. TEG variables including R- and K-time (clot formation), maximum amplitude (MA) and &#x3b1;-angle (clot stability), G value (clot elasticity), and EPL, A, and LY30 (fibrinolysis), as well as overall assessment of coagulation (coagulation index - CI), were measured before and at 0.5-48&#xa0;h after the treatments. TEG parameters did not change significantly in the control groups, except for CI parameter after choline administration. Endotoxemia resulted in increased R-time and A value (P&#xa0;<&#xa0;0.05), decreased K-time (P&#xa0;<&#xa0;0.05), &#x3b1;-angle (P&#xa0;<&#xa0;0.001) and CI values (P&#xa0;<&#xa0;0.01) at different time points. Treatment with either choline or CDP-choline attenuated or prevented completely the alterations in TEG parameters in endotoxemic dogs with CDP-choline being more effective. These results confirm and extend the effectiveness of choline or CDP-choline in endotoxemia by further demonstrating their efficacy in attenuating or preventing the altered viscoelastic properties of blood clot measured by TEG.