Prevention of rapid reperfusion-induced lung injury with prostaglandin E-1during the initial period of reperfusion

We have found that the instantaneous restoration of blood flow causes acute dysfunction and massive edema in rat lungs after 4 hours of room temperatu re ischemia. This is associated with an early increase in pulmonary artery pressure (P-pa) and can be prevented by a stepwise increase in flow rate du ring the first 10 minutes of reperfusion. The objectives of this study were to determine whether rapid reperfusion causes lung injury after hypothermi c preservation, and whether this injury can be attenuated by a short-course of prostaglandin E-1 (PGE(1)). Rat lungs were flushed preserved with low-p otassium dextran solution for 12 hours at 4 degrees C and randomly divided into three groups: (1) control (no PGE(1)); (2) PGE(1) only in the flush so lution; and (3) PGE(1) in both flush solution and blood perfusate during th e first 10 minutes of reperfusion. Post-preservation pulmonary function was assessed in an isolated rat lung reperfusion model developed previously. W e found that rapid initiation of reperfusion led to significant pulmonary d ysfunction, which was attenuated by a short-course of PGE(1) in the blood p erfusate. The addition of PGE(1) to the Bush solution alone did not have su ch an effect. Administration of PGE(1) to the blood perfusate during the fi rst 10 minutes resulted in significant lower P-pa and airway pressure and b etter gas exchange. There was a positive correlation between the peak P-pa during the first 10 minutes of reperfusion and the final shunt fraction. Th e physical forces generated by the rapid initiation of blood reperfusion ap pear to induce severe injury. The first 10 minutes of reperfusion seem to b e a transition phase in which mechanical factors play an important role rel ating to ultimate post reperfusion lung function. A short course of PGE(1) may be a useful maneuver to prevent rapid reperfusion-induced lung injury.