Effect of some new thioglycosides on endotoxin-induced disseminated intravascular coagulation in rabbits.
Disseminated intravascular coagulation (DIC) is a systemic thrombohemorrhagic disorder seen in association with many clinical situations, e.g. sepsis, malignancy, obstetrical complications and intravascular hemolysis. In our model, disseminated intravascular coagulation was induced in rabbits by two consecutive intravenous bolus injections of endotoxin from Escherichia coli, 80 and 40 microg/kg. The control group was treated with 0.9% saline. The activity of thioglycosides was compared to unfractionated heparin (UFH) and efegatran with and without administration of endotoxin. Drugs were administered in the following doses: heparin 50 and 100 IU/kg/h i.v. infusion; efegatran 0.25 and 0.5 mg/kg/h i.v. infusion; GYKI 39521 (RGH-1875) as well as GYKI 39541 (RGH-1962) 12.5 and 25 mg/kg per os. Thioglycosides did not modify coagulation parameters in this model [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT)] as compared with endotoxin/vehicle group. The changes in TFPI level after administration of thioglycosides and heparin were similar in the mentioned model to those without endotoxin. Endotoxin-induced changes of leukocyte count were not affected by GYKI 39521 and GYKI 39541 treatment in our model. Diminution of fibrinogen level and platelet count was prevented by GYKI 39521 and GYKI 39541. Fibrin degradation products and fibrinolysis were significantly decreased by GYKI 39521 and GYKI 39541. The thioglycosides may have a lower risk of bleeding in the treatment of disseminated intravascular coagulation than heparin.
Szabó
Gabriella
G
IVAX Drug Research Institute, PO Box 82, 1325 Budapest, Hungary.
Barabás
Eva
E
Kedves
Rita
R
Csomor
Katalin
K
Kuszmann
János
J
D000704:Analysis of Variance; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000188:drug therapy*; D004731:Endotoxins / Q000633:toxicity; D006493:Heparin / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D011817:Rabbits; D013865:Thioglycosides / Q000494:pharmacology*
C477865:4'-(methylthioiminomethyl)phenyl-1,5-dithioxylopyranoside; C477866:4'-nitrophenyl-1,5-dithioarabinopyranoside; D000925:Anticoagulants; D004731:Endotoxins; D009842:Oligopeptides; D013865:Thioglycosides; C044101:endotoxin, Escherichia coli; D006493:Heparin; C064289:efegatran