Effects of dermatan sulfate, a heparin cofactor II mediated thrombin inhibitor, on the endotoxin-induced disseminated intravascular coagulation model in the rat: comparison with low-molecular weight heparin, nafamostat mesilate and argathroban.
Effects of dermatan sulfate (DS) on the endotoxin-induced disseminated intravascular coagulation (DIC) rat model were compared with those of low-molecular weight heparin (LMWH), nafamostat mesilate (NM) and argathroban (AR). At doses of 5, 10 or 20 mg/kg/4 hr, DS significantly ameliorated the decrease of fibrinogen (Fbg), the increase of fibrin-fibrinogen degradation products (FDP) and except at the highest dose (20 mg/kg/4 hr), the prolongation of thrombin clotting time (TCT). It also decreased the glomerular fibrin deposits (%GFD) at doses of 10 or 20 mg/kg/4 hr. LMWH suppressed the decrease of Fbg and the increase of FDP at doses of 1.4 or 2.8 mg/kg/4 hr. Only the highest dose of LMWH suppressed the decrease of the platelet count (PL), the prolongation of prothrombin time, and improved the %GFD. AR suppressed the decrease of PL and improved the %GFD. At the dose required to improve the %GFD, DS (5, 10 mg/kg/4 hr) significantly suppressed the prolongation of TCT, which is related to the bleeding frequency, while LMWH and AR further increased the prolongation of the TCT. These results suggest that DS has potential as a therapeutic drug with a lower hemorrhagic risk as compared with LMWH and AR in the treatment of DIC.
Onaya
J
J
Tokyo Research Institute, Seikagaku Corporation, Higashiyamato, Japan.
Kyogashima
M
M
Sunose
A
A
Miyauchi
S
S
Mizuno
S
S
Horie
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D001550:Benzamidines; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000188:drug therapy*; D004731:Endotoxins / Q000633:toxicity; D006146:Guanidines / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use*; D015844:Heparin Cofactor II / Q000627:therapeutic use*; D008297:Male; D008970:Molecular Weight; D010875:Pipecolic Acids / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides
D001550:Benzamidines; D004731:Endotoxins; D006146:Guanidines; D010875:Pipecolic Acids; D013449:Sulfonamides; D003871:Dermatan Sulfate; D015844:Heparin Cofactor II; D006493:Heparin; D001120:Arginine; C031942:argatroban; C032855:nafamostat