title: Effects of FK3311 on pulmonary ischemia-reperfusion injury in a canine model.
abstract: BACKGROUND
  This study investigated the effects of a selective COX-2 inhibitor, FK3311, on warm ischemia-reperfusion (I/R) injury in the canine lung.
  
  
  METHODS
  Sixteen adult mongrel dogs were used in this study. In the FK group (n = 8), FK (1 mg/kg) was administered intravenously 15 min before ischemia and 15 min before reperfusion. In the control group (n = 8), a vehicle was injected in the same manner. Warm ischemia was induced for 3 h by clamping the left pulmonary artery, veins, and bronchus. Five-minute clamping tests of the right pulmonary artery were performed before ischemia and 30 min after reperfusion. During the test, left pulmonary vascular resistance (L-PVR), cardiac output (CO), and arterial oxygen pressure (PaO(2)) were measured. The lung specimens were simultaneously harvested for wet-to-dry weight ratio (WDR) measurements, histopathological studies, and polymorphonuclear neutrophil (PMN) counts. Serum thromboxane (Tx) B(2) and 6-keto-prostaglandin (PG) F(1alpha) (stable metabolites of TxA(2) and PGI(2), respectively) were also measured 30 min after reperfusion.
  
  
  RESULTS
  L-PVR, CO, PaO(2), and WDR were significantly (P < 0.05) better in the FK group than in the control group. Histological tissue edema was mild, and PMN infiltration was significantly (P < 0.05) reduced in the FK group compared to the control group. The serum TxB(2) levels were significantly (P < 0.05) lower in the FK group than in the control group, while 6-keto-PGF(1alpha) levels were not significantly (P < 0.05) reduced. Two-day survival rate was significantly (P < 0.05) better in the FK group than in the control group.
  
  
  CONCLUSIONS
  FK has protective effects on pulmonary I/R injury stemming from marked inhibition of TxA(2).
authors.affiliation: Second Department of Surgery, Gunma University School of Medicine, 3-39-15 Showa-Machi, Gunma, Maebashi, 371-8511, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sunose
authors.forename: I
authors.initials: I
authors.lastname: Takeyoshi
authors.forename: H
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: K
authors.initials: K
authors.lastname: Kawata
authors.forename: M
authors.initials: M
authors.lastname: Tokumine
authors.forename: S
authors.initials: S
authors.lastname: Iwazaki
authors.forename: N
authors.initials: N
authors.lastname: Tomizawa
authors.forename: S
authors.initials: S
authors.lastname: Ohwada
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D011464:Epoprostenol / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011651:Pulmonary Artery; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011667:Pulmonary Veins; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; C085566:FK 3311; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010100:Oxygen