Hepatic oxygen metabolism in porcine endotoxemia: the effect of nitric oxide synthase inhibition

The role of endotoxin (lipopolysaccharide, LPS) and nitric oxide in hepatic oxygen metabolism was investigated in 36 pigs receiving 1) LPS (1.7 mu g . kg(-1). h(-1)) for 7 h and N-G-nitro-L-arginine methyl ester (L-NAME; 25 m g/kg) after 3 h, 2) LPS, 3) NaCl and L-NAME, and 4) NaCl. Infusion of LPS r educed hepatic oxygen delivery (Do(2)H) 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 ((V) over dot o(2)H) was maintained (18 +/- 4 and 21 +/- 4 ml/min, change not significant ), but acidosis developed. Administration of L-NAME during endotoxemia caus ed further reduction of Do(2)H 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 (V) over dot o(2)H from 13 +/- 2 to 9 +/- 2 ml/min that did not reach statistical significance, probably re presenting a type II error. Acidosis was aggravated. Administration of L-NA ME in the absence of endotoxin also increased the hepatic oxygen extraction ratio, but no acidosis developed. In a different experiment, liver blood f low was mechanically reduced in the presence and absence of endotoxin, comp arable to the flow reductions caused by L-NAME. The increase in hepatic oxy gen extraction ratio (0.34) and maximum hepatic oxygen extraction ratio (si milar to 0.90) was similar whether Do(2)H 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 extra ction ratio to almost maximum when oxygen delivery was reduced. The effect oft-NAME on oxygen transport thus seems to be caused by a reduction in Do(2 )H rather than by alterations in oxygen extraction capabilities.