Efleet of Endotoxin on the Activity of Coagulation Factors VII, VIII and IX Produced during Organ Perfusion

Abstract

SummaryThe effect of bacterial endotoxin on the production of factor VII, VIII and IX activities in isolated rabbit livers, spleens and kidneys was investigated. The organs were perfused for 4 hours with fluid devoid of coagulation activity and containing either endotoxin or glucose-saline diluent. A series of parallel experiments included an initial hour of perfusion to ensure removal of tissue-stored coagulation activity, and perfusion with platelet-rich plasma and protein synthesis inhibitors. Endotoxin increased factor VII production in all organs but especially in livers not subjected to the initial perfusion; this effect was abolished by actinomycin D and puromycin. Endotoxin had little effect on hepatic factor VIII and IX activities but it inhibited production of both factors in the kidney and of factor VIII in the spleen. Initial perfusion prevented this inhibition of splenic factor VIII activity. These data suggest that endotoxin increases factor VII synthesis and causes consumption of factors VIII and IX in perfused kidneys and, to a lesser extent, spleens. Also, initial perfusion appears to prevent the subsequent consumption of splenic factor VIII by endotoxin. This response may involve activation of some tissue-bound or stored factor(s) or may be due to removal of an inhibitor substance.