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 nitri c oxide (NO) on hepatic oxygen delivery and consumption. After 3 h of endotoxemia, NO biosynthesis was modulated by a bolus dose of the NO s ynthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME). Fifteen minutes thereafter a continuous infusion of the NO donor sodium nitrop russide (SNP) was started. Endotoxin significantly reduced hepatic oxy gen 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 unaf fected. 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 t o 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 co ntrol group of 9 pigs which was treated in the same way as the study g roup, except for the SNP infusion. SNP induced an almost selective inc rease in hepatic arterial flow, with a corresponding increase in oxyge n delivery to 1.8 +/- 0.3 ml/kg/min (p < 0.05). At the same time ER wa s reduced from 68 to 42% (p < 0.05). Oxygen consumption remained unalt ered. The control group exhibited no change in either oxygen delivery or consumption. The study shows that nonselective inhibition of NO syn thesis is detrimental to hepatic perfusion and oxygen transport. The N O donor SNP increased oxygen delivery via a selective increase in hepa tic arterial flow, but failed to influence oxygen consumption. This wa s probably mainly due to a massive shutdown of sinusoids, which did no t reopen when flow was increased. A functioning microcirculation thus seems to be a prerequisite for the stimulation of organ blood flow to be effective.