Amelioration of post-ischemic lung reperfusion injury by prostaglandin E₁

To reduce ischemia-reperfusion injury, a number of clinical lung transplant programs employ prostaglandin E₁ (PGE₁) or prostacyclin (PGI₂) before donor lung flush and harvest. The effect of prostaglandins on the reperfusion component of this ischemia-reperfusion complex is unknown. We investigated the effect of PGE₁ given only during the period of reperfusion, on ischemic lung injury in an in situ rabbit model. To examine the mechanisms involved, we measured pulmonary hemodynamics as well as myeloperoxidase, circulating platelet, and tumor necrosis factor (TNF) values. Two hours of warm ischemia of the left lung was produced in anesthetized New Zealand white rabbits. The animals were randomly allocated into four groups based on treatment received only during reperfusion: PGE₁, PGI₂, nitroprusside (NP), or no treatment (controls). After 2 h of reperfusion, Pa(O₂) in the PGE₁ group was significantly 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 PGI₂ group was still significantly higher than that in controls. Wet/dry lung weight ratios were significantly lower in the PGE₁ and PGI₂ groups (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 lung myeloperoxidase activity in the four groups. We speculate that the beneficial 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 PGE₁ on platelets, neutrophils, or TNF suppression.