Addition of a neutrophil elastase inhibitor to the organ flushing solution decreases lung reperfusion injury in rat lung transplantation.
BACKGROUND
Neutrophil elastase plays an important role in ischemia-reperfusion injury. We hypothesized that the addition of sivelestat, a specific neutrophil elastase inhibitor, to the organ flushing solution would decrease reperfusion injury in a rat single left-lung transplant model.


METHODS
All donor lungs were flushed with 25 ml low-potassium dextran-glucose solution and stored for 16 h at 4 degrees C. Rats were divided into three experimental groups (n=10) that received donor lungs washed in either normal flushing solution (group 1), or flushing solution containing 20mg sivelestat (group 2) or 40 mg sivelestat (group 3). Graft function was assessed 48 h after reperfusion using five measurements: isolated graft oxygenation, wet/dry ratio, peak airway pressure, tissue myeloperoxidase activity, and serum lipid peroxides level. Histological examination of lung grafts was also performed.


RESULTS
Group 3 showed better oxygenation (groups 1, 2, and 3: 133.9+/-113.5, 254.0+/-84.6, and 378.7+/-77.6 mmHg, respectively; p<0.0001 vs group 1, p=0.0052 vs group 2), lower peak airway pressure (groups 1, 2, and 3: 28.7+/-6.1, 26.0+/-5.8, and 21.5+/-5.3 mmHg, respectively; p=0.0385 vs group 1), lower wet/dry ratio (groups 1, 2, and 3: 6.74+/-0.78, 5.77+/-0.52, and 4.90+/-0.16, respectively; p=0.0010 vs group 1), and lower myeloperoxidase activity (groups 1, 2, and 3: 0.304+/-0.081, 0.178+/-0.053, and 0.106+/-0.029 DeltaOD/mg/min, respectively; p<0.0001 vs group 1, p=0.0319 vs group 2). No significant differences in arterial PaCO(2) and serum lipid peroxide levels were observed between the three groups.


CONCLUSIONS
Addition of sivelestat to the organ flushing solution ameliorated ischemia-reperfusion injury in a lung transplant model.
Mori
Hideaki
H
Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama City, Japan. hmori-ths@umin.ac.jp
Nagahiro
Itaru
I
Osaragi
Tomohiko
T
Kotani
Kazutoshi
K
Nakanishi
Hidehiro
H
Sano
Yoshifumi
Y
Date
Hiroshi
H
Shimizu
Nobuyoshi
N
D000818:Animals; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D008168:Lung / Q000098:blood supply*; D016040:Lung Transplantation; D008297:Male; D023421:Models, Animal; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions / Q000592:standards; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
D019188:Organ Preservation Solutions; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine