Neutrophil modulation results in improved pulmonary function after 12 and 24 hours of preservation

Neutrophils are important mediators of reperfusion injury, and suppression of neutrophil function or numbers can reduce reperfusion injury and improve long-term organ preservation in transplantation. NPC 15669, a leumedin, is a novel compound that prevents recruitment of neutrophils at inflammatory foci by inhibiting CD11b/ CD18 adhesion molecule expression. NPC 15669 was used to inhibit neutrophil adhesion during reperfusion of isolated rabbit lungs after 12 and 24 hours of cold storage. Lungs (New Zealand White male rabbits, 2 to 3 kg) were flushed with 4°C Euro-Collins (EC) solution, harvested en bloc, stored under various study conditions, and reperfused for 3 hours with fresh whole blood at 37°C in an isolated perfusion system at constant flow and an inspired oxygen fraction of 1. Four groups (n = 6 each) were studied. Group I underwent immediate whole blood reperfusion. Group II were stored for 12 hours in 4°C EC solution before reperfusion. Group III were stored for 12 hours in 4°C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg whole body weight). Group IV were stored for 24 hours in 4°C EC solution and reperfused with whole blood containing NPC 15669 (10 mg/kg). Pulmonary artery and peak airway pressures were significantly lower and compliance higher in groups III and IV lungs after 3 hours of reperfusion (p < 0.05) compared with group I. Group I and III lungs had significantly less edema than group II (p < 0.05). The arterial partial pressure of oxygen was similar in all stored groups (II to IV). Inhibition of neutrophil adhesion with NPC 15669 during reperfusion of the isolated lung after long-term cold storage significantly improves pulmonary function. This study suggests a clinical means by which pulmonary injury during reperfusion can be ameliorated.