Role of Pulmonary Vasodilators in Ameliorating Primary Graft Dysfunction Following Lung Transplant

Abstract

In the blinded randomized clinical trial by Ghadimi et al, 1 inhaled epoprostenol was reported to be equivalent to inhaled nitric oxide (iNO) in preventing severe grade 3 primary graft dysfunction (PGD-3). While institution-specific contracts greatly influence the cost of iNO, it is generally an expensive therapy. The authors argue that the equivalence observed in the study end points justifies the use of the less expensive inhaled epoprostenol as an alternative to iNO for prophylaxis against PGD.However, it is important to understand that PGD is a syndrome and ischemia-reperfusion injury is but one of its multiple causes. Allo-or autoimmunity, donor pneumonia, structural damage to the allograft, or other injury mechanisms releasing damage-and pathogen-associated molecular patterns also contribute to the pathogenesis of PGD independent of ischemia-reperfusion injury, for which pulmonary vasodilators may be ineffective. The multifactorial cause of human PGD probably contributes to the discordance between the encouraging animal studies that have used models of pure ischemia-reperfusion injury and clinical trials where consistent benefit has not been observed with prophylactic iNO. At present, more clinical studies, 2-4 including a meta-analysis, 5 have failed to show efficacy of iNO in the prevention of PGD. Additionally, owing to the vasodilatory properties of iNO, concerns have been expressed that it could increase pulmonary edema and worsen PGD. Accordingly, pulmonary vasodila-