title: Prevention of rapid reperfusion-induced lung injury with prostaglandin E1 during the initial period of reperfusion.
abstract: We have found that the instantaneous restoration of blood flow causes acute dysfunction and massive edema in rat lungs after 4 hours of room temperature ischemia. This is associated with an early increase in pulmonary artery pressure (Ppa) and can be prevented by a stepwise increase in flow rate during the first 10 minutes of reperfusion. The objectives of this study were to determine whether rapid reperfusion causes lung injury after hypothermic preservation, and whether this injury can be attenuated by a short-course of prostaglandin E1 (PGE1). Rat lungs were flushed preserved with low-potassium dextran solution for 12 hours at 4 degrees C and randomly divided into three groups: (1) control (no PGE1); (2) PGE1 only in the flush solution; and (3) PGE1 in both flush solution and blood perfusate during the first 10 minutes of reperfusion. Postpreservation pulmonary function was assessed in an isolated rat lung reperfusion model developed previously. We found that rapid initiation of reperfusion led to significant pulmonary dysfunction, which was attenuated by a short-course of PGE1 in the blood perfusate. The addition of PGE1 to the flush solution alone did not have such an effect. Administration of PGE1 to the blood perfusate during the first 10 minutes resulted in significant lower Ppa and airway pressure and better gas exchange. There was a positive correlation between the peak Ppa during the first 10 minutes of reperfusion and the final shunt fraction. The physical forces generated by the rapid initiation of blood reperfusion appear to induce severe injury. The first 10 minutes of reperfusion seem to be a transition phase in which mechanical factors play an important role relating to ultimate post reperfusion lung function. A short course of PGE1 may be a useful maneuver to prevent rapid reperfusion-induced lung injury.
authors.affiliation: The Toronto Hospital, Department of Surgery, University of Toronto, Ontario, Canada.
authors.forename: K N
authors.initials: KN
authors.lastname: DeCampos
authors.forename: S
authors.initials: S
authors.lastname: Keshavjee
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: A S
authors.initials: AS
authors.lastname: Slutsky
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000527:Alprostadil / Q000008:administration & dosage*; D000818:Animals; D006801:Humans; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology / Q000517:prevention & control; D011659:Pulmonary Gas Exchange; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000527:Alprostadil