Feasibility of Lung Hypothermic Perfusion Without Ventilation: An Experimental Study

Hypothermic machine perfusion (HMP) is widely used to preserve kidney, liver, and heart grafts, improving post-transplant outcomes. However, its application to lung preservation remains unproven. This study investigates whether HMP can be transferred to lungs as an alternative to static cold storage (SCS).

In a paired-lung model, lungs from seven swine (n = 14) were randomly assigned to 6 h of either SCS at 4°C or pressure-controlled HMP at 10°C using Perfadex Plus. The HMP system provided continuous perfusion without ventilation or oxygenation at a target pressure of 5 mmHg. Preservation outcomes were assessed using graft weight variation, wet/dry ratio, cone-beam computed tomography, histology, endothelial permeability, biochemical markers, and cytokine levels.

Controlled-pressure HMP was technically feasible and maintained lung temperature at 11.3 ± 1.8°C. However, compared to SCS, HMP induced significantly greater edema (+39.9% versus -2.1%, P < 0.0001), confirmed by computed tomography scores (6.7 ± 1.6 versus 2.2 ± 1.6, P = 0.002) and histology (interlobular septal thickness 246 ± 215 μm versus 150 ± 135 μm, P = 0.015). Lactate and partial pressure of carbondioxide levels were higher, and glucose lower in the HMP perfusate. Interleukin-12/interleukin-23p40 levels were significantly elevated in the HMP group (P = 0.020). Partial pressure of oxygen remained high (200-250 mmHg), indicating preserved alveolar oxygen content. No significant differences were found in endothelial injury markers or vasodilatory responses.

Although HMP for lung grafts is feasible and preserves oxygen content, it is associated with significant interstitial edema when performed without ventilation or oxygenation. These findings suggest that direct transfer of HMP protocols from abdominal organs to the lung may require adaptation, particularly to prevent graft edema.