EFFECT OF COMBINED NITRIC-OXIDE INHALATION AND N-G-NITRO-L-ARGININE INFUSION IN PORCINE ENDOTOXIN-SHOCK

Objective: To evaluate the possible effects of a combination of system ic nitric oxide synthesis inhibition (to increase mean arterial blood pressure) and nitric oxide inhalation (to decrease pulmonary vascular pressure) in porcine endotoxin shock. Design: Prospective trial. Setti ng: Laboratory at a large university medical center. Subjects: Ten pat hogen-free pigs weighing 19 to 25 kg. Interventions: After surgical pr eparation, all pigs received a continuous infusion of Escherichia coli lipopolysaccharide endotoxin (15 mu g/kg/hr) for 2 hrs. After 1 hr of endotoxemia, nitric oxide inhalation (50 parts per million) and N-G-n itro-L-arginine infusion (50 mg/kg/hr) were initiated in six pigs. Fou r pigs served as controls and received only a lipopolysaccharide infus ion. Measurements and Main Results: N-G-nitro-L-arginine infusion and nitric oxide inhalation prevented the further decrease in mean arteria l blood pressure seen in the control pigs (p < .05), but did not resto re mean arterial blood pressure back to basal values. Cardiac output d ecreased significantly compared with controls during N-G-nitro-L-argin ine infusion/nitric oxide inhalation (p < .01). Systemic vascular resi stance, which was below basal values in the controls after 2 hrs of en dotoxemia, was markedly increased by N-G-nitro-L-arginine/nitric oxide , to higher values than those observed in the basal state (p < .01). I n the control pigs, mean pulmonary arterial pressure and pulmonary vas cular resistance showed a biphasic increase. In the N-G-nitro-L-argini ne/nitric oxide treated group, the second phase increase in mean pulmo nary arterial pressure did not occur (p < .01). However, there was no difference in pulmonary vascular resistance between the groups. Renal vascular resistance was unchanged in controls, while N-G-nitro-L-argin ine/nitric oxide induced a four-fold increase in renal vascular resist ance (p < .001). There was no statistical difference in urine producti on between the groups. Pao(2) values were higher and Paco(2) tensions were lower in the treated pigs than in the controls. Arterial pH and b ase excess did not differ. Arterial plasma epinephrine, norepinephrine , and neuropeptide Y concentrations increased during the lipopolysacch aride infusion in both groups, with a tendency toward higher concentra tions in the pigs receiving N-G-nitro-L-arginine/nitric oxide. Arteria l plasma endothelin-1-like immunoreactivity in these pigs was signific antly higher at the end of the treatment than in the controls. Conclus ions: In this model of porcine endotoxin shock, the combination of N-G -nitro-L-arginine infusion and nitric oxide inhalation attenuated pulm onary hypertension and improved gas exchange; it also prevented develo pment of further systemic hypotension, but impaired cardiac output and increased systemic and renal vascular resistances to supranormal leve ls. N-G-nitro-L-arginine/nitric oxide did not reduce sympathetic nervo us system activation or metabolic acidosis.