• T Saetre, Y Gundersen, O A Smiseth, T Scholz, H Carlsen, L Nordsletten, P Lilleaasen, T Sautner, R Függer, and A O Aasen.
• Institute for Surgical Research, The National Hospital, 0407 Oslo, Norway.
• Am. J. Physiol. 1998 Dec 1;275(6 Pt 1):G1377-85.

AbstractThe role of endotoxin (lipopolysaccharide, LPS) and nitric oxide in hepatic oxygen metabolism was investigated in 36 pigs receiving 1) LPS (1.7 microgram. kg-1. h-1) for 7 h and NG-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg) after 3 h, 2) LPS, 3) NaCl and L-NAME, and 4) NaCl. Infusion of LPS reduced hepatic oxygen delivery (DO2H) from 60 +/- 4 to 30 +/- 5 ml/min (P < 0.05) and increased the oxygen extraction ratio from 0.29 +/- 0.07 to 0.68 +/- 0.04 after 3 h (P < 0.05). Hepatic oxygen consumption (VO2H) was maintained (18 +/- 4 and 21 +/- 4 ml/min, change not significant), but acidosis developed. Administration of L-NAME during endotoxemia caused further reduction of DO2H from 30 +/- 3 to 13 +/- 2 ml/min (P < 0.05) and increased hepatic oxygen extraction ratio from 0.46 +/- 0.04 to 0.80 +/- 0.03 (P < 0.05). There was a decrease in VO2H from 13 +/- 2 to 9 +/- 2 ml/min that did not reach statistical significance, probably representing a type II error. Acidosis was aggravated. Administration of L-NAME in the absence of endotoxin also increased the hepatic oxygen extraction ratio, but no acidosis developed. In a different experiment, liver blood flow was mechanically reduced in the presence and absence of endotoxin, comparable to the flow reductions caused by L-NAME. The increase in hepatic oxygen extraction ratio (0.34) and maximum hepatic oxygen extraction ratio (approximately 0.90) was similar whether DO2H was reduced by occlusion or by L-NAME. We concluded that L-NAME has detrimental circulatory effects in this model. However, neither endotoxin nor L-NAME seemed to prevent the ability of the still circulated parts of the liver to increase hepatic oxygen extraction ratio to almost maximum when oxygen delivery was reduced. The effect of L-NAME on oxygen transport thus seems to be caused by a reduction in DO2H rather than by alterations in oxygen extraction capabilities.

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