Effects of FK3311 on pulmonary ischemia-reperfusion injury in a canine model

Background. This study investigated the effects of a selective COX-2 inhibi tor, FK3311, on warm ischemia-reperfusion (VR) injury in the canine lung. M aterials and Methods. Sixteen adult mongrel dogs were used in this study. In the FK grou p (n = 8), FK (1 mg/kg) was administered intravenously 15 min before ischem ia and 15 min before reperfusion. In the control group (n = 8), a vehicle w as injected in the same manner. Warm ischemia was induced for 3 h by clampi ng the left pulmonary artery, veins, and bronchus. Five-minute clamping tes ts of the right pulmonary artery were performed before ischemia and 30 min after reperfusion. During the test, left pulmonary vascular resistance (L-P VR), cardiac output (CO), and arterial oxygen pressure (PaO2) were measured . The lung specimens were simultaneously harvested for wet-to-dry weight ra tio (WDR) measurements, histopathological studies, and polymorphonuclear ne utrophil (PMN) counts. Serum thromboxane (Tx) B-2 and 6-keto-prostaglandin (PG) F-1 alpha (stable metabolites of TxA(2) and PGI(2) respectively) were also measured 30 min after reperfusion. Results. L-PVR, CO, PaO2 and WDR were significantly (P < 0.05) better in th e FK group than in the control group. Histological tissue edema was mild, a nd PMN infiltration was significantly (P < 0.05) reduced in the FK group co mpared 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(1 <alpha>) 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 contr ol group. Conclusions. FK has protective effects on pulmonary I/R injury stemming fro m marked inhibition of TxA(2). (C) 2001 Academic Press.