Donation After Circulatory Death Lungs Transplantable Up to Six Hours After Ex Vivo Lung Perfusion Eric J. Charles, MD, Mary E. Huerter, MD, MA, Cynthia E. Wagner, MD, Ashish K. Sharma, MBBS, PhD, Yunge Zhao, MD, PhD, Mark H. Stoler, MD, J. Hunter Mehaffey, MD, James M. Isbell, MD, MSCI, Christine L. Lau, MD, MBA, Curtis G. Tribble, MD, Victor E. Laubach, PhD, Irving L. Kron, MD The Annals of Thoracic Surgery Volume 102, Issue 6, Pages 1845-1853 (December 2016) DOI: 10.1016/j.athoracsur.2016.06.043 Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions
Fig 1 (A) Final oxygenation (partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2]) at the completion of 2 hours of reperfusion. (B) Dynamic compliance at the completion of 2 hours of reperfusion. Ex vivo lung perfusion (EVLP) group, transplantation at completion of EVLP; EVLP+Cold group, 6 hours cold preservation after EVLP and before transplantation; and Immediate group, immediate transplantation without EVLP. *p < 0.001 versus Immediate. #p < 0.025 versus. (cm H2o = centimeters of water; mm Hg = millimeters of mercury.) The Annals of Thoracic Surgery 2016 102, 1845-1853DOI: (10.1016/j.athoracsur.2016.06.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions
Fig 2 (A) Oxygenation (partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2]) and (B) dynamic compliance recorded hourly during ex vivo lung perfusion (EVLP). (C) Change in oxygenation and (D) dynamic compliance from start of EVLP to completion. EVLP group, transplantation at completion of EVLP; EVLP+Cold group, 6 hours cold preservation after EVLP and before transplantation; and Immediate group, immediate transplantation without EVLP. *p < 0.05. A and B, solid lines indicate EVLP; dashed lines indicate EVLP+Cold. C and D, dots indicate EVLP; squares indicate EVLP+Cold. (cm H2o = centimeters of water; mm Hg = millimeters of mercury; mL = milliliters.) The Annals of Thoracic Surgery 2016 102, 1845-1853DOI: (10.1016/j.athoracsur.2016.06.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions
Fig 3 Oxygenation (partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2]) recorded at four timepoints: donor animal before hypoxia (Pre-Hypoxia), 1 hour into ex vivo lung perfusion (EVLP [1-hour EVLP]), at the completion of EVLP (4-hour EVLP), and recipient after 2 hours of reperfusion (Post-Reperfusion). EVLP group (dashed line), transplantation at completion of EVLP; EVLP+Cold group (dotted line), 6 hours cold preservation after EVLP and before transplantation; and Immediate group (solid line), immediate transplantation without EVLP. *p < 0.001 for groups EVLP and EVLP+Cold versus immediate. (mm Hg = millimeters of mercury.) The Annals of Thoracic Surgery 2016 102, 1845-1853DOI: (10.1016/j.athoracsur.2016.06.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions
Fig 4 Tissue cytokine levels after reperfusion. Ex vivo lung perfusion [EVLP] group (striped bars) transplantation at completion of EVLP; EVLP+Cold group (open bars), 6 hours cold preservation after EVLP and before transplantation; and Immediate group (solid bars), immediate transplantation without EVLP. *p < 0.05 versus Immediate. (IFN = interferon; IL = interleukin; pg/mL = picograms per milliliter.) The Annals of Thoracic Surgery 2016 102, 1845-1853DOI: (10.1016/j.athoracsur.2016.06.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions
Fig 5 Pulmonary edema after reperfusion determined by tissue wet/dry weight ratios. Ex vivo lung perfusion (EVLP) group, transplantation at completion of EVLP; EVLP+Cold group, 6 hours cold preservation after EVLP and before transplantation; Immediate group, immediate transplantation without EVLP; and recipient pneumonectomy (PN). *p = 0.01 versus PN. The Annals of Thoracic Surgery 2016 102, 1845-1853DOI: (10.1016/j.athoracsur.2016.06.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions
Fig 6 (A) Representative histologic sections stained with hematoxylin and eosin (40× magnification). (B) Lung injury severity scores by histologic component and composite. Details of score determination can be found in Table 1. Ex vivo lung perfusion (EVLP) group (striped bars), transplantation at completion of EVLP; EVLP+Cold group (open bars), 6 hours cold preservation after EVLP and before transplantation; Immediate group (solid bars), immediate transplantation without EVLP; and recipient pneumonectomy (PN) group (checkered bars). *p < 0.02 versus PN. (PMN/HPF = polymorphonuclear neutrophils per high-powered field.) The Annals of Thoracic Surgery 2016 102, 1845-1853DOI: (10.1016/j.athoracsur.2016.06.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions
Fig 7 Neutrophil immunohistochemistry. (A) Representative sections (40× magnification). (B) Neutrophil counts per high-powered field (HPF). Ex vivo lung perfusion (EVLP) group, transplantation at completion of EVLP; EVLP+Cold group, 6 hours cold preservation after EVLP and before transplantation; Immediate group, immediate transplantation without EVLP; and recipient pneumonectomy (PN) group. #p < 0.01 versus Immediate. The Annals of Thoracic Surgery 2016 102, 1845-1853DOI: (10.1016/j.athoracsur.2016.06.043) Copyright © 2016 The Society of Thoracic Surgeons Terms and Conditions