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

J Thorac Cardiovasc Surg. 2017 Nov;154(5):1811-1820. doi: 10.1016/j.jtcvs.2017.02.072. Epub 2017 Apr 12.

Charles EJ¹, Mehaffey JH¹, Sharma AK¹, Zhao Y¹, Stoler MH², Isbell JM¹, Lau CL¹, Tribble CG¹, Laubach VE¹,Kron IL³. (Department of Surgery, University of Virginia Health System, Charlottesville, Va. Electronic address:ilk@virginia.edu.

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 A_2Breceptor 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/cmH₂O, P = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmH₂O, 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.

KEYWORDS: adenosine A2B receptor antagonism; donation after circulatory death; ex vivo lung perfusion; lung transplantation; porcine lung transplant model. PMID: 28483262 DOI:10.1016/j.jtcvs.2017.02.072