The effect of inducible nitric oxide synthase (iNOS) inhibition on smoke inhalation injury in sheep

Recent studies on smoke inhalation injury have been focused on nitric oxide (NO) as an essential factor of progressive lung injury. We studied the eff ects of inducible nitric oxide synthase (iNOS) inhibition on inhalation inj ury in sheep. Sheep (n = 14) were prepared surgically for chronic study. Af ter recovery period, the sheep received 48 breaths of cotton smoke. The ani mals were then randomised into two groups: MEG group [30 mg/kg mercaptoethy lguanidine (MEG), selective inhibitor of iNOS and peroxynitrite scavenger, was given 1 h after injury and then 8 h for 41 h, n = 7] and control group (0.9% NaCl, n = 7). All animals were ventilated mechanically, and airway bl ood flow was measured using colored microspheres. In the control group, fol lowing significant increase in airway blood flow, deterioration in the PaO2 /FiO(2) ratio was observed. Whereas in the MEG group, it was not observed. In addition, the MEG group did not show significant increase in pulmonary v ascular resistance and intrapulmonary shunt fraction. Lung wet/dry ratios, a marker of pulmonary edema, were significantly lower in the MEG group. At 48 h after injury, lung tissue-conjugated dienes, an index of lung oxidativ e tissue injury, were significantly lower in the MEG group than in the cont rol group. Our data suggest that 1) iNOS-NO produced in the airway circulat ion plays a major role on the significant increase in airway blood flow, wh ich may contribute to the spread of injury from injured airway to the lung parenchyma; 2) iNOS-NO induced in the pulmonary circulation contributes to the loss of hypoxic pulmonary vasoconstriction; and 3) iNOS-NO plays an imp ortant role on the lung oxidative tissue injury.