Effects of the COX-2 inhibitor FK3311 on ischemia - reperfusion injury in the rat lung.
Ischemia-reperfusion injury is induced by activation of the arachidonic acid cascade following the induction of cyclooxygenase-2. This study evaluated the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury in the lung. Male Wistar rats were divided into two groups. In the FK3311 group (n = 27), FK3311 (4 mg/kg) was administered intravenously 5 min before ischemia, while in the control group (n = 27) only vehicle was injected. Warm ischemia was induced for 1 h by clamping the left hilus. The arterial oxygen pressure (PaO(2)) and saturation (SaO(2)) were measured 30 and 120 min after reperfusion. Serum thromboxane B(2) and 6-keto-prostaglandin F(1alpha) were also measured 30 min after reperfusion. Lung specimens were harvested 120 min after reperfusion for histologic examination and polymorphonuclear counts, and immunostained with cyclooxygenase-2. The 1-week survival rate in the two groups was compared. PaO(2) and SaO(2) 30 and 120 min after reperfusion were significantly (p < .05) better in the FK3311 group. Serum thromboxane B(2) levels were significantly (p < .05) lower in the FK3311 group. However, there was no significant difference in 6-keto-prostaglandin F(1alpha). Histologically, tissue damage was mild and polymorphonuclear infiltration was reduced in the FK3311 group compared to the control group. The expression of cyclooxygenase-2 in the alveolar epithelium based on immunostaining was suppressed in the FK3311 group. The 1-week survival rate was significantly (p < .05) higher in the FK3311 group. We conclude that FK3311 has protective effects on pulmonary ischemia-reperfusion injury, and results in improvement in the 1-week survival rate.
Otani
Yoshimi
Y
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma,Japan.
Takeyoshi
Izumi
I
Yoshinari
Daisuke
D
Matsumoto
Koshi
K
Morishita
Yasuo
Y
D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D008171:Lung Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010100:Oxygen / Q000097:blood; D011650:Pulmonary Alveoli / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015996:Survival Rate; D013929:Thromboxane B2 / Q000097:blood
D000813:Anilides; D016861:Cyclooxygenase Inhibitors; C085566:FK 3311; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D010100:Oxygen