Ex Vivo Assessment of Porcine Donation After Circulatory Death Lungs That Undergo Increasing Warm Ischemia Times

Abstract

Background: Increased utilization of donation after circulatory death (DCD) lungs may help alleviate the supply/demand mismatch between available donor organs and lung transplant candidates. Using an established porcine DCD model, we sought to determine the effect of increasing warm ischemia time (WIT) after circulatory arrest on lung function during ex vivo lung perfusion (EVLP).

Methods: Porcine donors (n = 15) underwent hypoxic cardiac arrest, followed by 60, 90, or 120 minutes of WIT before procurement and 4 hours of normothermic EVLP. Oxygenation, pulmonary artery pressure, airway pressure, and compliance were measured hourly. Lung injury scores were assessed histologically after 4 hours of EVLP.

Results: After EVLP, all 3 groups met all the criteria for transplantation, except for 90-minute WIT lungs, which had a mean pulmonary artery pressure increase greater than 15%. There were no significant differences between groups as assessed by final oxygenation capacity, as well as changes in pulmonary artery pressure, airway pressure, or lung compliance. Histologic lung injury scores as well as lung wet-to-dry weight ratios did not significantly differ between groups.

Conclusions: These results suggest that longer WIT alone (up to 120 minutes) does not predict worse lung function at the conclusion of EVLP. Expanding acceptable WIT after circulatory death may eventually allow for increased utilization of DCD lungs in procurement protocols.

FIGURE 1

Physiologic changes during hypoxia from ET tube clamp to circulatory arrest. pH, PaCO₂, PaO₂, HCO₃, base excess, and lactic acid are shown. The horizontal shading indicates normal ranges for each parameter. The vertical dashed line indicates the mean time of death (22.2 minutes). Curves are shown with 95% confidence interval.

FIGURE 2

MAP and heart rate during hypoxia from ET tube clamp to circulatory arrest. The horizontal shading indicates normal ranges. The vertical dashed line indicates the mean time of death (22.2 minutes). Curves shown with 95% confidence interval.

FIGURE 3

Changes in oxygenation and PA pressure during EVLP. A, Hourly PO₂/FiO₂ during EVLP. B, Mean percent change of PO₂/FiO₂. C, Change in PO₂/FiO₂ for each animal per group. D, Hourly PA pressure. E, Mean percent change of PA pressure. F, Change in PA pressure for each group. Groups 60 WIT, 90 WIT, and 120 minutes WIT, lungs procured after hypoxic cardiac arrest and 60, 90, or 120 minutes of warm ischemia.

FIGURE 4

Changes in airway pressures during EVLP. A, Hourly plateau airway pressures. B, Mean percent change in plateau airway pressure. C, Change in plateau airway pressures for each animal per group. D, Hourly peak airway pressures. E, Mean percent change in peak airway pressure. F, Change in peak airway pressures for each animal per group. Groups 60 WIT, 90 WIT, and 120 minutes WIT, lungs procured after hypoxic cardiac arrest and 60, 90, or 120 minutes of warm ischemia.

FIGURE 5

Changes in compliance during EVLP. A, Hourly static compliance. B, Mean percent change in static compliance. C, Change in static compliance for each animal per group. D, Hourly dynamic compliance. E, Mean percent change in dynamic compliance. F, Change in dynamic compliance for each animal per group. Groups 60 WIT, 90 WIT, and 120 minutes WIT, lungs procured after hypoxic cardiac arrest and 60, 90, or 120 minutes of warm ischemia.

FIGURE 6

Lung histology at the end of EVLP. A, Representative H&E sections (20× magnification). B, Lung injury severity scores. Groups 60 WIT, 90 WIT, and 120 minutes WIT, lungs procured after hypoxic cardiac arrest and 60, 90, or 120 minutes of warm ischemia.