Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death.
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.
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va.
Cynthia E
CE
Wagner
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va.
Nicolas H
NH
Pope
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va.
Eric J
EJ
Charles
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va.
Mary E
ME
Huerter
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va.
Ashish K
AK
Sharma
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va.
Morgan D
MD
Salmon
School of Medicine, University of Virginia, Charlottesville, Va.
Benjamin T
BT
Carter
Department of Pathology, University of Virginia, Charlottesville, Va.
Mark H
MH
Stoler
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va.
Christine L
CL
Lau
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va.
Victor E
VE
Laubach
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Va. Electronic address: ilk@virginia.edu.
Irving L
IL
Kron
D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D003080:Cold Temperature; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D023421:Models, Animal; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010477:Perfusion; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D043705:Receptor, Adenosine A2A / Q000187:drug effects* / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D034421:Sus scrofa; D013997:Time Factors; D014021:Tissue Preservation / Q000379:methods*; D020858:Tissue and Organ Harvesting
D058908:Adenosine A2 Receptor Agonists; D016207:Cytokines; D019188:Organ Preservation Solutions; D043705:Receptor, Adenosine A2A
adenosine A2A receptor agonist; donation after cardiac death; ex vivo lung perfusion; lung transplantation; prolonged cold preservation