An experimental study of the recovery of injured porcine lungs with prolonged normothermic cellularex vivolung perfusion following donation after circulatory death

Abstract

Donation after circulatory death (DCD) is an underused source of donor lungs. Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving standard donor lungs but may also be useful in the preservation and assessment of DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm ischemia and postmortem ventilation on graft recovery were evaluated. Adult male swine underwent general anesthesia and heparinization. In the control group (n = 4), cardioplegic arrest was induced and the lungs were procured immediately. In the four treatment groups, a period of agonal hypoxia was followed by either 1 h of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on EVLP were worse in all DCD lungs compared with controls. Hemodynamics and compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated impaired oxygenation. Normothermic cellular EVLP is effective in preserving and monitoring of DCD lungs. Early donor postmortem ventilation and timely procurement lead to improved graft function.

Lung transplant after prolonged ex vivo lung perfusion: predictors of allograft function in swine

“…Before EVLP, the only testing platform for extended‐criteria donor lungs was the recipient. EVLP now allows evaluation, preservation, and reconditioning of these organs prior to transplant . We have previously demonstrated that the hemodynamics and compliance of swine DCD lungs normalize relative to standard donors during 24H normothermic EVLP, although more injured lungs had worse oxygenation .…”

“…Notably absent from our study are donors subjected to unventilated warm ischemia. This decision was made based on our previous data demonstrating superior EVLP performance of donor lungs preserved following ventilated warm ischemia . We do not believe that the procurement, preservation, and transplant of lungs from a donor that experiences prolonged warm unventilated ischemia comports to any realistic clinical scenario.…”

“…Our group has reported a methodology for preserving swine lungs for ≤24 hours (H) using blood‐based normothermic EVLP and have studied and reconditioned lungs subjected to severe DCD insults (≤2H of unventilated warm donor ischemia) . We have found that, despite a persistent oxygenation deficit, DCD lung physiology improves to levels equivalent to beating‐heart (analogous to DBD) donor lungs during prolonged preservation . The current study sought to characterize the correlation between data available during EVLP and acute post‐transplant allograft function.…”

Prolonged extracorporeal preservation and evaluation of human lungs with portable normothermic ex vivo perfusion

“…[14][15][16][17][18] Our group has reported experience with prolonged (~24 hours) preservation of porcine donor lungs from beating-heart and DCD donors in an acceptable functional state with the use of a portable normothermic EVLP system (Organ Care System [OCS] Lung [TransMedics]), combined with a perfusate based on autologous donor whole blood (ADWB) and a low-potassium dextran crystalloid solution (OCS Lung solution [TransMedics]). [19][20][21][22] While the most commonly considered measurement of allograft function when considering lung donors and during EVLP is the PaO 2 :FiO 2 (P:F) ratio, we have demonstrated the value of other measurements when evaluating the function of allografts from beating-heart and DCD donors during prolonged preservation, including pulmonary vascular resistance (PVR) and allograft edema formation. 19,21 In the current study, we replicated our model of prolonged preservation in a cohort of human donor lungs.…”

“…[19][20][21][22] While the most commonly considered measurement of allograft function when considering lung donors and during EVLP is the PaO 2 :FiO 2 (P:F) ratio, we have demonstrated the value of other measurements when evaluating the function of allografts from beating-heart and DCD donors during prolonged preservation, including pulmonary vascular resistance (PVR) and allograft edema formation. 19,21 In the current study, we replicated our model of prolonged preservation in a cohort of human donor lungs. We sought to identify and procure bilateral lung blocks from human donors that had been…”