A New Model for the Assessment of Lung Allograft Ischemia/Reperfusion Injury

Lung edema is the main clinical manifestation of reperfusion injury following lung transplantation. The evaluation of strategies to prevent this injury is of high clinical importance. Therefore we developed a large-animal model to study the mechanisms of ischemia/reperfusion injury including dynamics of posttransplant reperfusion edema and their prevention. Left lung allotransplantation was performed in 6 weight-matched pigs (25-31 kg). Donor lungs were flushed with 1.5 L low-potassium dextran (LPD) solution (4^oC) and preserved for 20 h at 1^oC. One hour after reperfusion the recipient contralateral right lung was excluded from perfusion and ventilation to assess graft function only. Extravascular lung water index (EVLWI), intrathoracic blood volume (ITBV), and cardiac output (CO) were assessed (q = 30 min) with a lung water computer (Cold Z-021, Partig, Munich, Germany) by the thermo-dye technique during a 5-h observation period. Gas exchange (FIO₂ = 1.0) was measured hourly, and hemodynamics were monitored continuously. The EVLWI of the recipient contralateral lung together with the donor left lung at the time of reperfusion was 6.5 +/- 1.1 ml/kg, increasing to 7.1 +/- 1.0 ml/kg at 60 min after reperfusion. After occlusion of the recipient right lung, EVLWI in the graft further increased within 80 min from 8.1 +/- 0.5 ml/kg to a peak of 11.4 +/- 1.3 ml/kg, followed by a decrease to 8.5 +/- 0.8 ml/kg at 5 h after reperfusion in 5 of 6 animals. In 1 animal a severe alveolar edema developed with subsequent deterioration of gas exchange and death 4.5 h after reperfusion. In this animal, peak EVLWI reached 16.8 ml/kg, PaO₂ deteriorated from 60.1 to 7.8 kPa, and CO decreased from 3.1 to 1.4 L/min. In all other animals, ITBV (515 +/- 51 ml), left atrial pressure (LAP), central venous pressure (CVP), and CO (2.9 +/- 0.3 L/min) were stable during the 5-h assessment period. We conclude that EVLWI measurement is a reliable and very sensitive method to quantify lung allograft reperfusion edema. It may prove useful in early assessment of lung allograft reperfusion injury in the clinical setting and in experimental models.