Intravascular Clearance of Endotoxin in Warfarin—treated Rabbits

Abstract

The primary elimination from circulating blood of intravenously administered endotoxin, and the primary distribution of the phagocytised endotoxin have been compared in warfarinpretreated and untreated rabbits. The results show that the elimination rate of endotoxin is significantly higher in warfarin‐treated rabbits than in untreated. The difference is, however, small, and does not reflect a significant difference in the organ distribution although the amounts of endotoxin in the organs are somewhat higher in the warfarin‐treated animals. Twenty min after injection about 75 per cent of the injected endotoxin has been eliminated from circulation, and about 50 per cent of the injected dose is located to the liver. The highest amount of endotoxin per g tissue is, however, found in the lungs. Twenty min after injection the same percentage, about 90, of circulating endotoxin was in both groups located to the plasma phase. The fact that the clearance rate of endotoxin in warfarin‐treated rabbits in higher than in untreated rabbits is thought to be due to the existence of a competitive phagocytosis of endotoxin and fibrin clots and not to a changed endotoxinplatelet interaction.

Intravascular Clearance of Endotoxin in Warfarin—Treated Rabbits

“…When the effect of warfarin treatment on the organ distribution of endotoxin is considered it should firstly be noted that the relative weights of some organs, especially the liver, (Tables 3 and 5 ) are significantly lower in the two warfarin-treated groups than in the untreated one. In a previous experiment (12) without immune serum administration no difference was found between absolute and relative weights of warfarintreated and untreated rabbits. The difference obtained in the present work may therefore in some way be due to different changes taking place in the organs of warfarin-treated and untreated rabbits after immune serum administration e. g. a different tissue reaction and/or a different blood flow provoked by the antigen-antibody complexes (4, 22).…”

“…without injection of immune serum was found to be significantly lower than for the first recorded period (4%-8fi min.) (12). The effect of immune serum is therefore even more marked than the curves (Fig.…”

“…In all groups the liver is dominant with regard to organ localization (Table 4). This organ has a considerably higher endotoxin content-both absolute and relative to other organs-than was obtained without immune serum (12). Carey et al (4) found a higher amount of endotoxin in the liver of tolerant rabbits-irrespective of dose and antibody titre, than in nontolerant ones.…”

“…In a previous study (12) a short pretreatment of rabbits with warfarin sodium gave an increased intravascular clearance and somewhat higher organ localization of intravenously administered endotoxin. In that study (12) the rabbits were nontolerant and no specific antibodies against the injected endotoxin influenced the clearance and the distribution in organs. In the presence of specific antibodies in blood there is an increased clearance rate and a changed organ uptake of endotoxin in non-warfarin-treated rabbits (4, 14).…”

“…Intravenously administered endotoxin disturbs the dynamic equilibrium of the coagulation system; a decrease in the function of the reticuloendothelial system (R. E. S.) (12) and changes in several other mechanisms taking place concurrently (18). In a previous study (12) a short pretreatment of rabbits with warfarin sodium gave an increased intravascular clearance and somewhat higher organ localization of intravenously administered endotoxin.…”