title: Melagatran, a low molecular weight thrombin inhibitor, counteracts endotoxin-induced haemodynamic and renal dysfunctions in the pig.
abstract: Coagulation and fibrinolysis are crucial in septic shock and inhibition of thrombin may be beneficial in this circumstance. Since porcine endotoxaemia has been found to replicate severe septic shock, a low molecular weight thrombin inhibitor, melagatran, was infused during the first 3 out of 6 h of endotoxaemia in pigs. Plasma creatinine (p <0.01) and urinary output (p <0.05) were less affected in the melagtran + endotoxin group (n=6) as compared to endotoxaemic controls (n=9). The left ventricular stroke work index, systemic vascular resistance index and oxygen extraction were all less affected (p <0.05) by endotoxin during the infusion of melagatran. The plasma concentration of melagatran declined with an apparent plasma half-life of 5 h as soon as the infusion was stopped. APTT, however, continued to increase after the infusion of melagatran had stopped and reached a maximum of 113 s at 5 h (baseline 17 s). APTT in endotoxaemic control pigs reached a maximum of 22 s. Thus, melagatran may counteract some consequences of endotoxaemia.
authors.affiliation: Department of Anaesthesiology and Intensive Care, University Hospital, Uppsala, Sweden. Mats.Eriksson@anestesi.uu.se
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.forename: T
authors.initials: T
authors.lastname: Saldeen
authors.forename: C
authors.initials: C
authors.lastname: Mattsson
mesh_terms: D000818:Animals; D001384:Azetidines; D001596:Benzylamines; D001777:Blood Coagulation / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004231:Diuresis / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006207:Half-Life; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010314:Partial Thromboplastin Time; D010976:Platelet Count / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy*; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D001384:Azetidines; D001596:Benzylamines; D005343:Fibrinolytic Agents; C109573:melagatran; D003404:Creatinine; D013917:Thrombin; D005998:Glycine