Effect of a cyclooxygenase-2 inhibitor, FK3311, in a canine lung transplantation model.
BACKGROUND
In the process of ischemia-reperfusion, inflammatory cytokines and arachidonic acid metabolites are released and followed by tissue damage. FK3311 (FK) is a selective cyclooxygenase-2 inhibitor that inhibits conversion of arachidonic acid into thromboxane A2 or prostaglandin I2. We investigated the effects of FK in canine lung transplantation.


METHODS
FK3311 was administered in the FK group, and vehicle was injected in the control group. The left lung was orthotopically transplanted after 12-hour preservation in Euro-Collins solution. After reperfusion, the right pulmonary artery and bronchus were ligated, and the animals were observed. Pulmonary gas exchange and hemodynamics were measured, histopathologic damages were investigated, and technetium-99m-labeled albumin scintigraphy was performed. The serum prostanoid levels were also measured.


RESULTS
In the FK group, pulmonary gas exchange and hemodynamics were significantly (p < 0.05) better, histologic damage and neutrophil infiltration was reduced, and technetium-99m-albumin accumulation was considerably suppressed. Also, thromboxane B2 was significantly (p < 0.05) lower, but 6-keto-prostaglandin F1alpha was not significantly reduced.


CONCLUSIONS
FK3311 generates protective effects on lung transplantation by a marked inhibition of thromboxane A2.
Sunose
Y
Y
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Takeyoshi
I
I
Tsutsumi
H
H
Ohwada
S
S
Oriuchi
N
N
Matsumoto
K
K
Morishita
Y
Y
D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000098:blood supply / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D015427:Reperfusion Injury / Q000473:pathology*; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D000813:Anilides; D016861:Cyclooxygenase Inhibitors; C085566:FK 3311; D013929:Thromboxane B2; D013928:Thromboxane A2