NITRIC-OXIDE INHALATION ATTENUATES PULMONARY-HYPERTENSION AND IMPROVES GAS-EXCHANGE IN ENDOTOXIN-SHOCK

Nitric oxide (10 ppm) inhaled by pigs before or during endotoxin shock induced by an infusion of E. coli lipopolysaccharide. Nitric oxide inhalation selectively attenuated pulmonary hypertension during endotoxin infusion without influencing mean arterial blood pressure and cardiac output. Upon cessation of nitric oxide inhalation, pulmonary artery pressure rapidly increased to levels seen in endotoxin-treated controls. The oxygenation and pH of arterial blood were significantly higher in the animals receiving nitric oxide. A marked increase in arterial plasma noradrenaline and neuropeptide Y was seen in endotoxin-treated control pigs while in the nitric oxide-treated pigs this increase was markedly reduced. The increase in arterial plasma endothelin-1 was not influenced by nitric oxide inhalation. Infusion of L-arginine (substrate for nitric oxide synthesis) also attenuated the pulmonary hypertension but was not selective for the pulmonary vasculature. L-Nitro-arginine (a nitric oxide synthesis inhibitor) initiated a rapid but brief elevation of arterial blood pressure and of pulmonary artery pressure as well as a reduction in cardiac output. Nitric oxide inhalation selectively reduces pulmonary hypertension in porcine endotoxin shock and improves arterial oxygenation and pH with a marked attenuation of sympathetic activation.