INVIVO QUANTITATION OF THE RAT LIVERS ABILITY TO ELIMINATE ENDOTOXIN FROM PORTAL-VEIN BLOOD

  • 1 January 1982
    • journal article
    • research article
    • Vol. 32  (6) , 409-422
Abstract
The in vivo uptake of [Escherichia coli] endotoxin by the liver from portal vein blood was assessed during a single passage through the liver. 51Cr labeled and unlabeled endotoxin were infused in different amounts into the femoral vein of 3 groups of lead-sensitized rats: a nonoperated, a sham-operated, and a surgically created reversed Eck fistula (REF) group. Whereas in the former 2 the infused endotoxin encounters the lung as the first filter organ, the liver performs this function in the latter experimental model. The mortality rates observed in control and sham-operated, lead-sensitized rats were found to correlate closely and reproducibly to the degree of endotoxemia. This assay was then applied to determine the amount of endotoxin eliminated by the liver by establishing, in the REF rat, the amounts of endotoxin that escaped hepatic clearance. Following infusion of 1 .mu.g of endotoxin/h into REF rats, .apprx. 985 ng is found to be taken up by the liver; following 2 .mu.g, 1965 ng is sequestered; following 3 .mu.g, 2810 ng; and after 4 .mu.g, 3175 ng is retained by the liver. Hence, the capacity of the liver to eliminate endotoxin from portal vein blood during a single passage increases as the portal vein endotoxin level rises; it approaches a maximum, suggesting that endotoxin''s interaction with the Kupffer cells conforms to classical saturation kinetics. A Lineweaver-Burk plot prepared from these data indicates that the maximal in vivo capacity of the liver to remove endotoxin from portal vein blood approximates 1.5 .mu.g/g liver/h. Data obtained with the use of radiolabeled endotoxin corroborate the information obtained with the bioassay technique. Endotoxin eliminated by the Kupffer cells in these quantities is slowly disintegrated; 4 h after termination of the endotoxin infusion, < 4% of the radiolabel is found in the urine and none in the bile. Evidently, the Kupffer cell''s functional capacity to sequester and detoxify endotoxin is extensive and far exceeds the requirements imposed by physiological and most pathological conditions.

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