Lungs donated after circulatory death and prolonged warm ischemia are transplanted successfully after enhanced ex vivo lung perfusion using adenosine A2B receptor antagonism

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 154; no. 5; pp. 1811 - 1820
• Main Authors: Charles, Eric J., MD, Mehaffey, J. Hunter, MD, Sharma, Ashish K., MBBS, PhD, Zhao, Yunge, MD, PhD, Stoler, Mark H., MD, Isbell, James M., MD, MSCI, Lau, Christine L., MD, MBA, Tribble, Curtis G., MD, Laubach, Victor E., PhD, Kron, Irving L., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2017
• Subjects: adenosine A2B receptor antagonism; Cardiothoracic Surgery; donation after circulatory death; ex vivo lung perfusion; lung transplantation; porcine lung transplant model; A 2BR; pulmonary artery; ex vivo lung perfusion; EVLP; FiO 2; adenosine A2B receptor antagonism; porcine lung transplant model; high-powered field; adenosine A 2B receptor; interleukin; left atrial/atrium; partial pressure of oxygen; primary graft dysfunction; IL; DCD; PaO 2; IR; PGD; BAL; PA; LA; fraction of inspired oxygen; lung transplantation; donation after circulatory death; ex vivo lung perfusion; bronchoalveolar lavage; ischemia−reperfusion; HPF; FiO2; PaO2; A2BR
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/j.jtcvs.2017.02.072

Abstract Objective The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. Methods Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP. ATL802, an adenosine A2B receptor antagonist, was administered to select groups. Four groups (n = 4/group) were randomized: cold preservation (Cold), cold preservation with ATL802 during reperfusion (Cold + ATL802), EVLP (EVLP), and EVLP with ATL802 during ex vivo perfusion (EVLP + ATL802). Lungs subsequently were transplanted, reperfused, and assessed by measuring dynamic lung compliance and oxygenation capacity. Results EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP (25.0 ± 1.8 vs 17.0 ± 2.4 mL/cmH2 O, P  = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P  = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmH2 O, P  = .002). Oxygenation capacity was highest in EVLP (440.4 ± 37.0 vs Cold: 174.0 ± 61.3 mm Hg, P  = .037). No differences in oxygenation or pulmonary edema were observed between EVLP and EVLP + ATL802. A significant decrease in interleukin-12 expression in tissue and bronchoalveolar lavage was identified between groups EVLP and EVLP + ATL802, along with less neutrophil infiltration. Conclusions Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donor cardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality.