Protective effects of ONO-5046*Na, a specific neutrophil elastase inhibitor, on postperfusion lung injury

Background. Polymorphonuclear neutrophil elastase might contribute to postperfusion lung injury, so we evaluated the protective effect of ONO-5046·Na, a specific inhibitor of polymorphonuclear neutrophil elastase, against such an injury.

Methods. The study was done using 8 mongrel dogs that received ONO-5046·Na (15 mg/kg per hour) (group O) and 8 control dogs (group C), all of which had 1 hour of partial bypass and 5 hours of observation.

Results. The respiratory index showed no significant changes in group O, but increased significant in group C (1.4 ± 2.0 versus 5.1 ± 4.7, p = 0.0047). Pulmonary extravascular water volume increased markedly in group C but only slightly in group O (group C 20.6 ± 8.7, group O 11.2 ± 2.7 mL/kg; p = 0.0005). Blood concentrations of polymorphonuclear neutrophil elastase and interleukin-6 showed more than a tenfold increase in group C (PMN elastase, group C 12.9 ± 12.8, group O 2.4 ± 1.3 ng/mL; IL-b, group C 11.0 ± 9.3, group O 2.9 ± 3.8 pg/mL; p < 0.05) but were only slightly higher in group O. Histologic examination revealed interstitial and intraalveolar edema in group C, but group O was virtually normal.

Conclusions. ONO-5046·Na inhibits polymorphonuclear neutrophil elastase and maintains better pulmonary function, so it should reduce postperfusion lung injury.