Effect of inhaled nitric oxide on endotoxin-induced hypoxaemia in rabbits.

In five mechanically ventilated rabbits, we studied the property of inhaled nitric oxide in helping to treat hypoxaemia which was induced by intravenous endotoxin (Escherichia coli-derived lipopolysaccharide, serotype 0111: B4). We used measurements of arterial partial pressure of oxygen to check a therapeutic nitric oxide benefit. Pulmonary artery pressure was continuously monitored. Furthermore, we determined the single-breath diffusing capacity for nitric oxide. Measurements of plasma nitrite/nitrate concentration served as an indicator of endogenous nitric oxide output. The first infusion of endotoxin led to a transient pulmonary vasoconstriction, whereas arterial partial pressure of oxygen was permanently reduced by 30 +/- 10 mmHg (mean +/- SD), attaining minimal values of 48 +/- 3.4 mmHg due to additional endotoxin. Single-breath diffusing capacity for nitric oxide declined by 20 +/- 5.5% of baseline values until the experiments were concluded. Endotoxin induced an increase in plasma nitrite/nitrate concentration in the five rabbits as well as in the control animals (four rabbits) without exogenous nitric oxide supply. During the 25 inhalations of nitric oxide (3-50 ppm), arterial oxygenation did not change significantly. Thus endotoxin permanently impaired pulmonary gas exchange without inducing pulmonary hypertension. Inhaled nitric oxide did not improve arterial oxygenation during endotoxaemia.