Attenuation of endothelium-dependent dilation of pig pulmonary arterioles after cardiopulmonary bypass is prevented by monoclonal antibody to complement C5a

We examined whether pulmonary endothelial dysfunction associated with cardi opulmonary bypass (CPB) may be mediated by complement Cia in pigs, Pigs Mer e placed on normothermic CPB for 1 h with or without a previous administrat ion of 1.6 mg/kg anti-C5a monoclonal antibody (MAb), then reperfused for 2 h. Pulmonary tissue myeloperoxidase activity was measured. Expression of ni tric oxide synthase (NOS) was measured by reverse transcriptase polymerase chain reaction and Western blotting. Pulmonary arterioles approximately 100 mu m in diameter were preconstricted with the thromboxane analog U46619 1 mu M, and relaxation responses to adenosine diphosphate 10(-9)-10(-4) RI, s ubstance P 10(-12)-10(-6) M, and sodium nitroprusside 10(-9)-10(-4) hi were examined in vitro by videomicroscopy. Relaxation to the endothelium-depend ent dilators adenosine diphosphate and substance P was attenuated after CPB ; this attenuation was prevented by the previous administration of MAb. Rel axation to sodium nitroprusside was not;affected by CPB, Neutrophil sequest ration, as measured by MPO activity, increased after CPB, either with or wi thout MAb. Transcription of NOS was unchanged by CPB, but translation of co nstitutive NOS was decreased after CPB, and this decrease was prevented by a Previous administration of MAb, We conclude that pig pulmonary endothelia l dysfunction associated with CPB may be mediated by C5a. The mechanism may involve changes in NOS translation. Implications: In Figs, pulmonary endot helial dysfunction may occur after cardiopulmonary bypass due to product(s) of complement activation.