Effects of Ventilation During Warm Ischemia in a Rat Lung Perfusion Model

Suitable donor shortage for lung transplantation and limiting criteria of circulatory death donors calls for the expansion of donor criteria. A critical parameter for lung quality is oxygenation. We investigated the influence of ventilation on lung injury resulting from circulatory death utilizing a lung perfusion protocol.

Circulatory dead male Wistar rats were ventilated or not for 30 min during warm ischemia. Lungs were either placed in cold storage for 2 h; or perfused in situ for 2 h with Perfadex in an open circuit (37°C). Perfusate was collected at 15 and 120 min of perfusion. Lung tissue was evaluated for inflammation and apoptosis. Lung fragments were placed in culture (24 h), and medium was used to measure cytokine concentration.

Cytokines were found elevated in the perfusate at the end of perfusion: tumor necrosis factor-α (P = 0.0312) and (interleukin (IL)-6 P = 0.0049). These cytokines in lung homogenates were higher in the perfused groups compared to their respective controls: tumor necrosis factor-α (P = 0.0036), IL 1-β (P = 0.0011), and IL-6 (P = 0.0595). Ventilation increased lung BAX (Bcl-2 associated X protein) expression in the control groups (P = 0.0248) and indicated a higher number of caspase-3-stained cells (P = 0.0185) when compared to the nonventilated groups. A decrease in hemorrhage was observed after perfusion in both groups (P < 0.0001).

Ventilation during warm ischemia seems to point to an increased apoptotic profile of donor lungs. Thus, early ventilatory strategies might not be necessary for graft maintenance, and the data presented supports the potential inclusion of uncontrolled circulatory dead donor lungs to expand the donor pool for transplantation.