Specific neutrophil elastase inhibitor does not attenuate acute lung injury induced by air embolism in awake sheep.

To investigate the role played by neutrophil-derived elastase in acute lung injury, this study examined the effects of treatment of ONO-5046, a competitive, reversible, and specific neutrophil elastase inhibitor, on lung dysfunction induced by air emboli in awake sheep. Sheep were prepared with chronic lung lymph fistula. In experiment 1, air (1.23 mL/min) was infused over a 2-h period into the pulmonary artery and hemodynamic monitoring was performed over a 5-h period. In experiment 2, air was infused in the same manner as in experiment 1, 1 h after the continuous infusion of ONO-5046 (10 mg/kg h-1) had begun. In experiment 1, pulmonary artery pressure (Ppa) increased from the baseline value of 17.0 +/- 0.7 cm H2O to 28.3 +/- 1.8 1 h after the beginning of the air infusion. Ppa returned to the baseline values within 1 h after the air infusion was stopped. Lung lymph flow (Qlym) increased from the baseline value of 3.7 +/- 0.7 mL/0.5 h to 8.5 +/- 1.9 after 1 h of air infusion. After the air infusion was stopped, Qlym continued to increase. When sheep were treated with ONO-5046, Ppa and Qlym increased in a fashion similar to that in the experiment 1. These findings suggest that ONO-5046 does not attenuate air embolism-induced lung injury and that neutrophil-derived elastase may not play an important role in air embolism-induced lung injury in awake sheep.