title: Initiation of white cell activation during cardiopulmonary bypass: cytokines and receptors.
abstract: The pathogenesis of organ injury induced by extracorporeal circulation involves many inflammatory cascades and cellular components of the immune system. One therapeutic approach is to target the neutrophil and minimize the deleterious effects of neutrophil activation during bypass. Mechanical removal of circulating neutrophils from the perfusate by filtration produced profound leukopenia in a dog model that persisted for 8-12 h post-bypass. The leukocyte-depleted animals had less lung sequestration of white cells than control animals and less evidence of white-cell activation. These differences resulted in significantly improved pulmonary gas exchange in the post-bypass period. Another approach to reducing cardiopulmonary bypass (CPB) neutrophil-mediated injury is modulation of neutrophil-endothelial adherence. One strategy is to improve the biocompatibility of the bypass circuit. Our laboratory measured the upregulation of the neutrophil-adhesion molecules CD11b and CD18 during CPB but did not demonstrate significant differences between membrane and bubble oxygenators. However, studies in pigs undergoing CPB with a standard extracorporeal circuit or a heparin-coated CPB circuit found less pulmonary injury in the heparin-coated group of animals. Specific therapy to inhibit adhesion molecule expression using the anti-inflammatory compound NPC 15669 has shown promise. Marked inhibition of neutrophil CD18 expression during and post-bypass, better gas exchange, and lower pulmonary vascular resistance occurred in the treated animals. The role of cytokines in relation to the morbidity associated with bypass is not clearly defined. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, and IL-8 are usually (but not uniformly) elevated after cardiac operations.
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors.forename: D
authors.initials: D
authors.lastname: Cameron
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D018375:Neutrophil Activation / Q000502:physiology*
chemical_list: D016207:Cytokines; D016023:Integrins