AMELIORATION OF POSTISCHEMIC LUNG REPERFUSION INJURY BY PROSTAGLANDIN-E1

To reduce ischemia-reperfusion injury, a number of clinical lung trans plant programs employ prostaglandin E1 (PGE1) or prostacyclin (PGI2) b efore donor lung flush and harvest. The effect of prostaglandins on th e reperfusion component of this ischemia-reperfusion complex is unknow n. We investigated the effect of PGE, given only during the period of reperfusion, on ischemic lung injury in an-in situ rabbit model. To ex amine the mechanisms involved, we measured pulmonary hemodynamics as w ell as myeloperoxidase, circulating platelet, and tumor necrosis facto r (TNF) values. Two hours of warm ischemia of the left lung was produc ed in anesthetized New Zealand white rabbits. The animals were randoml y allocated into four groups based on treatment received only during r eperfusion: PGE1, PGI2, nitroprusside (NP), or no treatment (controls) . After 2 h of reperfusion, Pa(O2), in the PGE, group was significantl y higher (423 +/- 52.7 mm Hg) than in all other groups (PGI2, 239 +/- 43.4, p < 0.05; NP, 146 +/- 14.2 p < 0.01; controls, 74 +/- 19.1 mm Hg , p < 0.01), despite similar pulmonary vascular resistance in the PGE1 and NP groups. Although lower than in the PGE1 group, Pa(O2) in the P GI2 group was still significantly higher than that in controls. Wet/dr y lung weight ratios were significantly lower in the PGE1 and PGI2 gro ups (6.5 +/- 0.2 [p < 0.01] and 6.9 +/- 0.6 [p < 0.05], respectively, versus 8.2 +/- 0.1 in controls). There were no significant differences in plasma TNF levels, platelet sequestration across the lungs, or lun g myeloperoxidase activity in the four groups. We speculate that the b eneficial effects of PGE1 may be due to a direct cytoprotective effect , since it did not appear to be due to its vasodilating properties or to the known effects of PGE, on platelets, neutrophils, or TNF suppres sion.