Neutrophil elastase inhibitor ameliorates reperfusion injury in a canine model of lung transplantation.
BACKGROUND
We investigated the effects of neutrophil elastase inhibitor ONO-5046 Na on lung ischemia-reperfusion injury in a canine model of single lung transplantation.


METHODS
24 mongrel dogs, 12 donors and 12 recipients, were used for single lung transplantation. Lung grafts were preserved for 18 h by cold ischemia then transplanted into the left thoracic cavity of recipients. In 6 recipients (ONO group), a bolus of ONO-5046 Na (10 mg/kg) was introduced before reperfusion and followed by continuous infusion (10 mg/kg/h). The remaining 6 recipients (control group) did not receive ONO-5046 Na and thus served as controls. We evaluated lung function and respiratory parameters over 240 min.


RESULTS
The total cell number in bronchoalveolar lavage fluid increased significantly in the control group in comparison to that in the ONO group. Histologic scores after 4 h of reperfusion and myeloperoxidase activity were significantly lower in the ONO group than in the control group.


CONCLUSIONS
Neutrophil elastase inhibitor ONO-5046 Na may be useful in ameliorating lung reperfusion injury after transplantation.
Aoki
T
T
Department of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan. taoki@med.niigata-u.ac.jp
Tsuchida
M
M
Takekubo
M
M
Saito
M
M
Sato
K
K
Hayashi
J
J
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004285:Dogs; D015633:Extravascular Lung Water / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics; D016040:Lung Transplantation / Q000473:pathology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology*
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine