• Joshua M Diamond, Mary K Porteous, Edward Cantu, Nuala J Meyer, Rupal J Shah, David J Lederer, Steven M Kawut, James Lee, Scarlett L Bellamy, Scott M Palmer, Vibha N Lama, Sangeeta M Bhorade, Maria Crespo, Ejigayehu Demissie, Keith Wille, Jonathan Orens, Pali D Shah, Ann Weinacker, David Weill, Selim Arcasoy, David S Wilkes, Lorraine B Ware, Jason D Christie, and Lung Transplant Outcomes Group.
• Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. joshua.diamond@uphs.upenn.edu
• Plos One. 2012 Jan 1; 7 (12): e51932.

IntroductionPrimary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD.MethodsWe performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE).ResultsThere were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40%) and 47 non-PGD subjects (59%) received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF). Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03). The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02); there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD) (p = 0.9).ConclusionsAngiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.

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