Abstract
The effect of the thromboxane A2 synthetase inhibitor, OKY-046 on pulmonary flushing and preservation of lung was studied using an ex vivo perfused rabbit model. The grafts were divided into the following groups : Group 1) flushed in vivo with modified EP4 solution (50 ml /kg) alone (n=10); and Group 2 flushed in vivo with modified EP4 solution (50 ml/kg) containing OKY-046 (0.1 mmol) (n=10). After preservation for 18 hours at 8t, the function of preserved grafts was examined for 60 seconds with autologous blood using an ex vivo perfusion system.
During flushing, the mean (± SD) pulmonary artery pressure (PAP) was significantly lower (p<0.005) in Group 2 (9.5±0.33 cmH2O) than in Group 1 (10.7±1.0 cmH2O). During reperfusion, the mean (± SD) PAP for Group 2 was significantly lower than that for Group 1 at each time point (p<0.01-0.04). During the 60 seconds of reperfusion, a direct significant correlation was found between time (X) and PAP (Y) in Group 2 (Y= -0.058, X +21.0 ; r= 0.486, p< 0.01). In the functional assessment of grafts, the mean (± SD) wet/dry weight ratio of reperfused lung for Group 2 (5.62 ± 0.27) was significantly lower than for Group 1 (6.47 ± 0.33) (p<0.001). The mean (±SD) pO2 of reperfused lung for Group 2 (144.6 ± 8.1 torr) was significantly higher than that for Group 1 (97.0±25.2 torr) (p<0.001).
The results of the present study show a significant effect of modified EP4 solution containing OKY-046 on lung preservation. There findings indicate a potential approach to ameliorate the effects of ischemia-reperfusion injury.
