Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death Read at the 95th Annual Meeting of the American Association for Thoracic Surgery, Seattle, Washington, April 25-29, 2015.

Cynthia E. Wagner, Nicolas H. Pope, Eric J. Charles, Mary E. Huerter, Ashish K. Sharma, Morgan D. Salmon, Benjamin T. Carter, Mark H. Stoler, Christine L. Lau, Victor E. Laubach, Irving L. Kron

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Objective Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion. Methods Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins. Results Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion. Conclusions After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation.

Original languageEnglish (US)
Pages (from-to)538-546
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume151
Issue number2
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Keywords

  • adenosine A2A receptor agonist
  • donation after cardiac death
  • ex vivo lung perfusion
  • Lung transplantation
  • prolonged cold preservation

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death Read at the 95th Annual Meeting of the American Association for Thoracic Surgery, Seattle, Washington, April 25-29, 2015.'. Together they form a unique fingerprint.

  • Cite this