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.
Yamazaki
T
T
Department of Thoracic Surgery, Nagoya University School of Medicine, Japan.
Ooshima
H
H
Usui
A
A
Watanabe
T
T
Yasuura
K
K
D000818:Animals; D002315:Cardiopulmonary Bypass; D004285:Dogs; D015633:Extravascular Lung Water / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000097:blood; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D010100:Oxygen / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D015850:Interleukin-6; D016209:Interleukin-8; D020011:Protective Agents; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D010100:Oxygen; D005998:Glycine