THE EFFECTS OF HYPEROXIA ON THE BIOSYNTHESIS OF CYCLOOXYGENASE PRODUCTS AND HEMODYNAMIC-RESPONSE TO NITRIC-OXIDE SYNTHASE INHIBITION WITH L-NAME IN ENDOTOXAEMIC PIGS

The interaction between constitutive nitric oxide and oxygen may depen d on the degree of tissue oxygenation and may play a critical role in the pathophysiological response to endotoxaemia, We investigated if hy peroxia (100% O-2) attenuated the systemic and pulmonary vasoconstrict ion and increased biosynthesis of thromboxane B-2 (TXB2) and 6-keto-pr ostaglandin (PG) F-1 alpha induced by inhibition of nitric oxide synth ase with N-G-nitro-L-arginine-methyl-ester (L-NAME) in a porcine model of endotoxaemia. Twenty-two domestic, random source pigs, weighing 15 .4 +/- 2.7 kg (mean +/- standard deviation) were the subjects of this study. Pigs were anaesthetized with isoflurane in 100% O-2 orotracheal ly intubated and ventilated to maintain normocapnia, and then instrume nted for haemodynamic monitoring. Following instrumentation, pigs were maintained at an end-tidal isoflurane concentration of 2%. Pigs were randomly assigned to treatment groups: saline + 30% O-2 (Control, n = 6); Escherichia coli lipopolysaccharide (5 mu g/kg/h from 1 to 2 h fol lowed by 2 mu g/kg/h from 2 to 5 h) + 30% O-2 (LPS, n = 4); L- NAME (0 .5 mg/kg/h, from 0 to 5 h) + LPS + 100% O-2 (n = 6); and L-NAME + LPS + 30% O-2 (n = 6), L-NAME and endotoxin significantly (P < 0.05) incre ased mean arterial pressure, mean pulmonary arterial pressure, and sys temic and pulmonary vascular resistance index beginning at 90 min. Whe n results were pooled across all time periods, mean arterial pressure and mean pulmonary arterial pressure were significantly higher in the L-NAME + LPS + 30% O-2 group than all other groups, reflecting pulmona ry and systemic vasoconstriction. Hyperoxia attenuated the L-NAME + LP S-induced increases in TXB2 and 6-keto-PGF(1 alpha) concentrations at 90 and 120 min and 120 min, respectively, although the differences wer e not statistically significant. These results support the observation that nitric oxide synthase inhibition with L-NAME has deleterious hae modynamic effects in this model of endotoxaemia. The temporal attenuat ion of L-NAME-induced pulmonary and systemic vasoconstriction by hyper oxia suggested that the haemodynamic effects of acute endotoxaemia wer e in part influenced by the relative amounts of nitric oxide and oxyge n present.