Early graft dysfunction continues to be a major clinical problem after lung transplantation. The objective of this experiment was to determine whether continuous administration of prostaglandin E(1) (PGE(1)) after lung transplantation has a beneficial effect on early graft function. Left lung allotransplantation was performed in 10 size-matched mongrel 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, followed by a pulmonary artery flush with 50 mL/kg of 4 degrees C modified Euro-Collins solution. The lungs were then stored at 1 degrees C for 12 hours. Left lung transplantation was performed using standard technique. The right pulmonary artery and right bronchus were ligated prior to chest closure. Animals were placed in the supine position and ventilated 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 implantation. The dose was gradually increased and fixed when mean systemic pressure 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-hour assessment period, arterial oxygen tension and alveolar-arterial oxygen pressure difference were preserved in group I compared with group II (group I versus group II: arterial oxygen tension, 255.8 +/- 37.6 mm Hg versus 64.7 +/- 7.9 mm Hg [p < 0.05]; alveolar-arterial oxygen pressure difference, 411.1 +/- 70.5 mm Hg versus 597.5 +/- 1.3 mm Hg [p < 0.05]). There were no significant differences in pulmonary circulatory hemodynamics between the two groups. Wet to dry lung weight ratio and 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 lung myeloperoxidase activity between the two groups. We conclude that PGE(1), significantly improved early lung function after transplantation and that this improvement is not due to pulmonary vasodilatation, improved pulmonary circulation, or inhibition of leukocyte activation.
