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.Materials and 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 (PaO2) 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) B2 and 6-keto-prostaglandin (PG) F1α (stable metabolites of TxA2 and PGI2, respectively) were also measured 30 min after reperfusion.Results. L-PVR, CO, PaO2, 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 TxB2 levels were significantly (P < 0.05) lower in the FK group than in the control group, while 6-keto-PGF1α 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 TxA2.