A new model for the assessment of lung allograft ischemia/reperfusion injury

Lung edema is the main clinical manifestation of reperfusion injury followi ng lung transplantation. The evaluation of strategies to prevent this injur y is of high clinical importance. Therefore we developed a large-animal mod el to study the mechanisms of ischemia/reperfusion injury including dynamic s of posttransplant reperfusion edema and their prevention. Left lung allot ransplantation was performed in 6 weight-matched pigs (25-31 kg). Donor lun gs were flushed with 1.5 L low-potassium dextran (LPD) solution (4 degrees C) and preserved for 20 h at 1 degrees C. One hour after reperfusion the re cipient contralateral right lung was excluded from perfusion and ventilatio n to assess graft function only. Extravascular lung water index (EVLWI), in trathoracic blood volume (ITBV), and cardiac output (CO) were assessed (q=3 0 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 (FIO 2 = 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 seve re alveolar edema developed with subsequent deterioration of gas exchange a nd death 4.5 h after reperfusion. In this animal, peak EVLWI reached 16.8 m l/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 stab le 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 reperfusi on injury in the clinical setting and in experimental models.