title: Melatonin does not affect disseminated intravascular coagulation but diminishes decreases in platelet count during subacute endotoxaemia in rats.
abstract: BACKGROUND
  Inhibitory effects of exogenous melatonin (MLT) on plasma coagulation and platelet aggregation have already been observed in vivo and in vitro under normal conditions. Here, we studied whether MLT also diminishes the lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) during subacute endotoxaemia.
  
  
  METHODS
  Subacute endotoxaemia was induced in male Wistar rats by an intravenous infusion of LPS over a period of 300min (0.5mg LPS/kg×h). MLT was administered intravenously 15min before and 120min and 240min after starting of the LPS infusion (3×3mg MLT/kg×15min). The kinetic of clot formation was analysed by thromboelastometry.
  
  
  RESULTS
  Infusion of LPS led initially to a significant reduction of clotting time (120min, LPS: 150±21s vs. SHAM: 292±36s), and finally a significant increase of clotting time (300min, LPS: 2768±853s vs. SHAM: 299±67s) and a slight increase of clot formation time (300min, LPS: 1038±657s vs. SHAM: 98±14s) as well as a significant decrease of alpha-angle (300min, LPS: 35±15° vs. SHAM: 72±3°), maximum clot firmness (300min, LPS: 22±6mm vs. SHAM: 68±3mm), and area under the curve (300min, LPS: 1657±552mm×100 vs. SHAM: 6849±307mm×100). Simultaneously, a decrease of platelet count (300min, LPS: 55±8 vs. SHAM: 180±55) and a release of cell-free haemoglobin (240min, LPS: 46±5μmol/L vs. SHAM: 16±2μmol/L) could be observed in the course of subacute endotoxaemia. The additional administration of MLT did not reduce the LPS-induced alterations in parameters of thromboelastometry, but significantly reduced the LPS-induced decrease of platelet count (300min, LPS+MLT: 130±10) and release of cell-free haemoglobin (240min, LPS+MLT: 29±3μmol/L).
  
  
  CONCLUSIONS
  Melatonin does not affect DIC but diminishes thrombocytopenia and haemolysis during endotoxaemia.
authors.affiliation: Institute for Physiological Chemistry, University Hospital Essen, Essen, Germany.
authors.forename: Maren Oude
authors.initials: MO
authors.lastname: Lansink
authors.affiliation: Department of Anaesthesiology and Intensive Care, University Hospital Essen, Essen, Germany; TEM International GmbH, Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Görlinger
authors.affiliation: Department of Anaesthesiology and Intensive Care, University Hospital Essen, Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hartmann
authors.affiliation: Institute for Physiological Chemistry, University Hospital Essen, Essen, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: de Groot
authors.affiliation: Institute for Physiological Chemistry, University Hospital Essen, Essen, Germany. Electronic address: katharina.effenberger-neidnicht@uni-duisburg-essen.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Effenberger-Neidnicht
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy*; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D006461:Hemolysis / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D008070:Lipopolysaccharides; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D010976:Platelet Count; D051381:Rats; D017208:Rats, Wistar; D013916:Thrombelastography; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications / Q000188:drug therapy
chemical_list: D008070:Lipopolysaccharides; D008550:Melatonin
keywords: Hemolysis; Lipopolysaccharide; Platelet; Sepsis; Thromboelastometry