Salutary effects of the prostacyclin analogue CG 4203 in lethal endotoxemia in rats.
In pentobarbitone anesthetized rats infusion of E. coli endotoxin (0.42 mg.kg-1.min-1 for 4 hours) produced 96% lethality within 6 hours. Transient decrease in mean arterial blood pressure, thrombocytopenia, leukopenia, loss of plasma fibrinogen, fibrin deposits in renal glomeruli, hemolysis and decrease in arterial oxygen tension and pH were observed. Infusion of the prostacyclin analogue CG 4203 (0.464 and 1.0 micrograms.kg-1.min-1 for 6 hours), starting concomitantly with the endotoxin infusion, improved the survival rate to 95 and 100%. Blood pressure during endotoxemia was slightly lower in CG 4203 treated rats than in vehicle controls. CG 4203 infusion marginally attenuated thrombocytopenia and obviously inhibited leukopenia, but did not effect fibrinogen consumption in endotoxemic rats. Incidence of glomerular fibrin deposits was dose dependently and significantly reduced by CG 4203. The lower dose reduced and the higher dose completely prevented the occurrence of hemolysis. Acidotic changes were not observed in CG 4203 treated endotoxin-shocked rats. Also with treatment starting 1 hour after the onset of endotoxemia CG 4203 in the same doses significantly inhibited the endotoxin-induced lethality. As protective mechanisms against lethal rat endotoxemia the prostacyclin-like hemodynamic, fibrinolytic, rheological and membrane stabilizing properties of CG 4203 are discussed.
Schneider
J
J
Grünenthal GmbH, Center of Research, Aachen, West Germany.
D000818:Animals; D003015:Clostridium Infections / Q000662:veterinary*; D004767:Enterotoxemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D004768:Enterotoxins / Q000633:toxicity*; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D004926:Escherichia coli; D005340:Fibrinogen / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D004768:Enterotoxins; C039188:taprostene; D005340:Fibrinogen; D011464:Epoprostenol