ADMINISTRATION OF PROSTAGLANDIN E(1) AFTER LUNG TRANSPLANTATION IMPROVES EARLY GRAFT FUNCTION

Early graft dysfunction continues to be a major clinical problem after lung transplantation. The objective of this experiment was to determi ne whether continuous administration of prostaglandin E(1) (PGE(1)) af ter lung transplantation has a beneficial effect on early graft functi on. Left lung allotransplantation was performed in 10 size-matched mon grel dogs (weight, 24.4 to 31.4 kg). Lung preservation consisted of a bolus injection of PGE(1) (250 mu g) into the pulmonary artery, follow ed by a pulmonary artery flush with 50 mL/kg of 4 degrees C modified E uro-Collins solution. The lungs were then stored at 1 degrees C for 12 hours. Left lung transplantation was performed using standard techniq ue. The right pulmonary artery and right bronchus were ligated prior t o chest closure. Animals were placed in the supine position and ventil ated for 6 hours with 100% oxygen at a rate of 20 breaths/min, a tidal volume of 550 mt, and a positive end-expiratory pressure of 5 cm H2O. Animals were randomly allocated to one of two groups. Group I animals (n = 6) received continuous PGE, infusion from the onset of implantat ion. The dose was gradually increased and fixed when mean systemic pre ssure showed a 10% decrease (mean PGE(1) dose, 31.7 +/- 6.9 ng.kg(-1). min(-1)). Group II animals (n = 4) received no PGE(1). After the 6-hou r assessment period, arterial oxygen tension and alveolar-arterial oxy gen pressure difference were preserved in group I compared with group II (group I versus group II: arterial oxygen tension, 255.8 +/- 37.6 m m Hg versus 64.7 +/- 7.9 mm Hg [p < 0.05]; alveolar-arterial oxygen pr essure difference, 411.1 +/- 70.5 mm Hg versus 597.5 +/- 1.3 mm Hg [p < 0.05]). There were no significant differences in pulmonary circulato ry hemodynamics between the two groups. Wet to dry lung weight ratio a nd fetal volume of airway edema fluid were also significantly less in group I than in group II (group I versus group II: wet to dry ratio, 8 .2 +/- 0.9 versus 12.1 +/- 0.7 [p < 0.01]; edema fluid, 106.7 +/- 38.6 mL versus 375.0 +/- 56.2 mL [p < 0.01]), There was no difference in l ung myeloperoxidase activity between the two groups. We conclude that PGE(1), significantly improved early lung function after transplantati on and that this improvement is not due to pulmonary vasodilatation, i mproved pulmonary circulation, or inhibition of leukocyte activation.