Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death  Cynthia E. Wagner,

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Ex Vivo Lung Perfusion with Adenosine A2A Receptor Agonist Decreases Ischemia-Reperfusion Injury in Donation after Cardiac Death CE Wagner, NH Pope, EJ.
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Presentation transcript:

Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death  Cynthia E. Wagner, MD, Nicolas H. Pope, MD, Eric J. Charles, MD, Mary E. Huerter, MD, Ashish K. Sharma, MBBS, PhD, Morgan D. Salmon, PhD, Benjamin T. Carter, BS, Mark H. Stoler, MD, Christine L. Lau, MD, MBA, Victor E. Laubach, PhD, Irving L. Kron, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 151, Issue 2, Pages 538-546 (February 2016) DOI: 10.1016/j.jtcvs.2015.07.075 Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Comparison of initial and final Pao2/Fio2 ratios among groups. Initial donor Pao2/Fio2 ratios were obtained before procurement. Final Pao2/Fio2 ratios of donor lungs were determined from samples obtained from the left superior and inferior pulmonary veins after 4 hours of reperfusion. *P < .0001 versus DMSO. Pao2/Fio2, Arterial oxygen partial pressure/fraction of inspired oxygen; DMSO, dimethyl sulfoxide; ATL-E, A2AR agonist administration during EVLP; ATL-E/R, A2AR agonist administration during EVLP and reperfusion. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 538-546DOI: (10.1016/j.jtcvs.2015.07.075) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Trends in Po2 gradients throughout 4 hours of EVLP in DMSO, ATL-E, and ATL-E/R groups. The red line represents the 350 mm Hg threshold for clinical lung transplantation. Po2, Oxygen tension; EVLP, ex vivo lung perfusion; DMSO, dimethyl sulfoxide; ATL-E, A2AR agonist administration during EVLP; ATL-E/R, A2AR agonist administration during EVLP and reperfusion. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 538-546DOI: (10.1016/j.jtcvs.2015.07.075) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Changes in physiologic parameters throughout 4 hours of EVLP. Peak airway pressure, dynamic compliance, and PVR in the DMSO, ATL-E, and ATL-E/R groups. EVLP, Ex vivo lung perfusion; DMSO, dimethyl sulfoxide; ATL-E, A2AR agonist administration during EVLP; ATL-E/R, A2AR agonist administration during EVLP and reperfusion. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 538-546DOI: (10.1016/j.jtcvs.2015.07.075) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Percent change in peak airway pressure, dynamic compliance, and PVR between the first hour and the fourth hour of EVLP among groups. The red line represents the 15% threshold for clinical lung transplantation. EVLP, Ex vivo lung perfusion; DMSO, dimethyl sulfoxide; ATL-E, A2AR agonist administration during EVLP; ATL-E/R, A2AR agonist administration during EVLP and reperfusion. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 538-546DOI: (10.1016/j.jtcvs.2015.07.075) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Proinflammatory cytokine levels in lung tissue after 4 hours of reperfusion. IL, Interleukin; IFN-γ, interferon gamma; DMSO, dimethyl sulfoxide; ATL-E, A2AR agonist administration during EVLP; ATL-E/R, A2AR agonist administration during EVLP and reperfusion. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 538-546DOI: (10.1016/j.jtcvs.2015.07.075) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 Pulmonary edema after 4 hours of reperfusion as measured by total protein concentration in BAL fluid and lung wet-to-dry weight ratios. BAL, Bronchoalveolar lavage; DMSO, dimethyl sulfoxide; ATL-E, A2AR agonist administration during EVLP; ATL-E/R, A2AR agonist administration during EVLP and reperfusion. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 538-546DOI: (10.1016/j.jtcvs.2015.07.075) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 7 Top, Representative lung histology (hematoxylin and eosin stain at 20× magnification) after 4 hours of reperfusion in DMSO, ATL-E, and ATL-E/R groups. Bottom, Comparison of mean lung injury severity scores among groups as determined from histology. DMSO, Dimethyl sulfoxide; ATL-E, A2AR agonist administration during EVLP; ATL-E/R, A2AR agonist administration during EVLP and reperfusion. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 538-546DOI: (10.1016/j.jtcvs.2015.07.075) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

The treated groups (ATL-E and ATL-E/R) had higher final Pao2/Fio2 ratios than the DMSO group. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 538-546DOI: (10.1016/j.jtcvs.2015.07.075) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions