[Improving effect of the synthetic protease inhibitor E-3123 on experimental DIC in dogs].
Disseminated intravascular coagulation (DIC) is a severe syndrome associated with generalized, intractable bleeding and multiple organ failure. Synthesized protease inhibitors such as gabexate mesilate and nafamostat mesilate show an improving effect on DIC, which develops by a chain reaction involving the coagulation, fibrinolysis, complement and kallikrein systems. Experimental DIC was developed in Beagle dogs by infusion of 150 U/kg tissue thromboplastin (Group I), and the improving effect of a new synthetic protease inhibitor, E-3123, was examined. The following groups of animals were treated with drugs: Group II (n = 4) was given with 5 mg/kg/hr of E-3123; group III (n = 4) was given 10 mg/kg/hr of E-3123; and group IV was given 6 mg/kg/hr of gabexate mesilate (GM). Although improvement of the hemodynamics or peripheral circulation was not apparent, a slight, but insignificant, improvement of lactate/pyruvate was noted in the treated groups. On the other hand, the hemostatic abnormalities such as prolongation of prothrombin time and activated thromboplastin time; decreases of platelet count, fibrinogen and alpha 2-antiplasmin; and increases of fibrin degradation products were significantly improved in the treated groups. These results indicate that E-3123 is effective for improving experimental DIC, and it is suggested that E-3123 is applicable for the treatment of clinical DIC.
Kazama
M
M
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Kobayashi
K
K
Tahara
C
C
Miyajima
Y
Y
Endo
Y
Y
Tanaka
H
H
Nakatani
T
T
Tajimi
K
K
D000818:Animals; D001780:Blood Coagulation Tests; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy*; D004285:Dogs; D016670:Gabexate / Q000494:pharmacology; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism; D011773:Pyruvates / Q000097:blood; D019289:Pyruvic Acid
D006146:Guanidines; D007773:Lactates; D011773:Pyruvates; C057059:4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate; D019344:Lactic Acid; D016670:Gabexate; D019289:Pyruvic Acid