Effect of a cyclooxygenase-2 inhibitor, FK3311, in a canine lung transplantation model

Abstract

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 A 2 or prostaglandin I 2. 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 B 2 was significantly ( p < 0.05) lower, but 6-keto-prostaglandin F 1α was not significantly reduced. Conclusions. FK3311 generates protective effects on lung transplantation by a marked inhibition of thromboxane A 2.