Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model

Hypothermia is critical for proper lung preservation. Ideally, the lungs should be maintained at the optimal preservation temperature during the entire ischemic interval. Lung rewarming during implantation is commonly observed. This study was undertaken to investigate the severity of rewarming ischemia on preservation injury and the possibility of minimizing this by use of leukocyte depletion during initial reperfusion.

Four experimental groups were tested as follows: neonatal piglet heart-lung blocks were either (1) placed on an isolated, blood-perfused, working heart-lung circuit without intervening ischemia (control, n = 6), (2) reperfused on the circuit with whole blood (WB, n = 6) after 13 hours of preservation, (3) reperfused with WB after 12 hours of preservation and 1 hour of rewarming (RWB, n = 5), or (4) reperfused with leukocyte-depleted blood for an initial 10 minutes followed by WB, after 12 hours of preservation and 1 hour of rewarming (n = 6). All groups were studied for 4 hours.

The partial pressure of arterial oxygen and lung compliance were significantly lower in the RWB group than in controls (113.8+/-33.1 vs 417.3+/-6.2 mm Hg, p < 0.01; and 0.8+/-0.2 vs 2.9+/-0.4 ml/cm H2O, p < 0.05, respectively). Pulmonary vascular resistance and lung wet/dry weight ratios were significantly higher in the RWB group than in controls (15884.1+/-11354.8 vs 6108.3+/-1309.9 dyne x sec x cm[-5], p < 0.05; and 7.13+/-0.24 vs 5.82+/-0.35, p < 0.05, respectively). The WB and leukocyte-depleted groups did not differ significantly from controls for any measured parameter.

This model confirms that rewarming ischemia during lung implantation exacerbates reperfusion injury. Leukocyte-depleted reperfusion as tested for a short period of time (10 minutes) ameliorates this injury and therefore should be considered for clinical lung transplantation.