NPC-15669 BLOCKS NEUTROPHIL CD18 INCREASE AND LUNG INJURY DURING CARDIOPULMONARY BYPASS IN PIGS

DURING cardiopulmonary bypass (CPB), neutrophils become activated due to contact with extracorporeal surfaces and binding of complement frag ments C3a and C5a, leading to extravasation and subsequent tissue dama ge. In this study, the effects of the leumedin NPC 15669 (N - [9H - (2 ,7 - dimethylfluorenyl - 9 - methoxy) carbonyl]-L-leucine), a leukocyt e recruitment inhibitor, were evaluated in a pig model of CPB. NPC 156 69 caused significant inhibition of CPB associated increase in CD18 up regulation, lung tissue myeloperoxidase content, and percentage wet we ight compared to controls. Lung histology revealed clear airways and m inimal neutrophil infiltration in treated animals vs. significant oede ma and cellular infiltration in controls. It is concluded that CPB cau ses a dramatic increase in neutrophil CD18, and that leumedins are eff ective in inhibiting neutrophil activation and subsequent tissue injur y when administered during CPB.