Modulators of nitric oxide in porcine endotoxemia: effects on hepatic oxygen delivery and consumption.
In a porcine model of endotoxemia we have studied the effects of nitric oxide (NO) on hepatic oxygen delivery and consumption. After 3 h of endotoxemia, NO biosynthesis was modulated by a bolus dose of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Fifteen minutes thereafter a continuous infusion of the NO donor sodium nitroprusside (SNP) was started. Endotoxin significantly reduced hepatic oxygen delivery from 3.4 +/- 0.6 to 2.2 +/- 0.3 ml/kg/min at 3 h. Due to an increased extraction ratio (ER), oxygen consumption was nearly unaffected. L-NAME further diminished oxygen delivery to 1.0 +/- 0.2 ml/kg/min within 15 min (p < 0.05), but despite an increase in ER from 47 to 68% (p < 0.05), oxygen consumption tended to decrease (from 1.0 to 0.7 ml/ kg/min, nonsignificant). A similar tendency was observed in a control group of 9 pigs which was treated in the same way as the study group, except for the SNP infusion. SNP induced an almost selective increase in hepatic arterial flow, with a corresponding increase in oxygen delivery to 1.8 +/- 0.3 ml/kg/min (p < 0.05). At the same time ER was reduced from 68 to 42% (p < 0.05). Oxygen consumption remained unaltered. The control group exhibited no change in either oxygen delivery or consumption. The study shows that nonselective inhibition of NO synthesis is detrimental to hepatic perfusion and oxygen transport. The NO donor SNP increased oxygen delivery via a selective increase in hepatic arterial flow, but failed to influence oxygen consumption. This was probably mainly due to a massive shutdown of sinusoids, which did not reopen when flow was increased. A functioning microcirculation thus seems to be a prerequisite for the stimulation of organ blood flow to be effective.
Gundersen
Y
Y
Institute for Surgical Research, Rikshospitalet, University of Oslo, Norway.
Saetre
T
T
Carlsen
H
H
Scholz
T
T
Lilleaasen
P
P
Aasen
A O
AO
D000818:Animals; D019446:Endotoxemia / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010101:Oxygen Consumption; D013552:Swine
D009599:Nitroprusside; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester