Effect of cardiopulmonary bypass on leukocyte activation: changes in membrane-bound elastase on neutrophils

Background: Neutrophil elastase is known to be released from the activated leukocytes as a result of cardiopulmonary bypass (CPB). However, its biological effect on organ injury is questionable because it is quickly bound by natural proteinase inhibitors (PIs). Recently, membrane-bound elastase ( MBE) was found to be able to resist the PIs' process and, thus, is biologically more active. This paper studies the effect of CPB on the kinetic change of MBE and its possible link to postoperative inflammation and organ function. Method: Ten consecutive patients undergoing elective coronary artery bypass grafting (CABG) surgery with CPB were recruited into the study. Blood samples were taken before sternotomy, after aortic declamping, at the end of CPB, three and six hours after CPB and on the first postoperative day. MBE was determined by substrate assay from isolated neutrophils. Inflammation and organ function markers were determined according to routine laboratory methods. Results: MBE slightly increased after aortic declamping, while it significantly increased and reached its peak at the end of CPB; it returned to its preoperative level on the first postoperative day. In contrast to lung sequestration of neutrophils, there was no transpulmonary gradient of MBE between left and right atria after aortic declamping. Neither MBE nor total MBE activity was positively correlated with postoperative inflammation markers such as blood lactate and C-reactive protein and organ function markers such as creatine phosphokinase and alanine aminotransferase. Conclusions: CPB induces increased MBE expression on neutrophils with its peak at the end of CPB. Lack of association between neutrophil MBE and clinical markers suggests that multiple systems might be involved in the post-CPB inflammatory reaction and organ dysfunction.