Cardiopulmonary bypass renders patients at risk for multiple organ failurevia early neutrophil priming and late neutrophil disability

Background. Cardiopulmonary bypass (CPB) is associated with a systemic infl ammatory response syndrome (SIRS) and these patients are recognized to be a t increased risk for delayed infectious complications. We have documented t hat circulating neutrophils (PMNs) from patients manifesting SIRS have evid ence of early postinjury priming for cytotoxicity. Consequently, we hypothe sized that CPB would result in early postoperative PMN hyperresponsiveness (priming). Materials and methods. Six patients (mean age 50 +/- 2.9 years) who underwe nt CPB for CABG had sequential blood samples obtained perioperatively. PMNs were isolated and superoxide anion (O-2(-)) generation (nmol O-2(-)/3.75 x 10(5) PMNs/min) was measured by reduction of cytochrome c after exposure t o fMLP, C5a, or PMA; elastase release (% total PMN elastase content) was me asured by cleavage of AAPV-pNA after exposure to fMLP or C5a. Results. PMNs were activated for increased elastase release 6 h after initi ation of CPB. Significant PMN priming for O-2(-) production was discovered at 3, 6, and 12 h following CPB and for elastase release at 3 and 6 h after CPB. At 2 to 3 days after CPB. O-2(-) generation was significantly less th an that of the preoperative control. Neutrophil primability with PAF was de tected at 6 h after CPB. A similar defect in PAF-primable O-2(-) production was seen 2 and 3 days post CPB. Direct PMN interrogation with the receptor -independent activator PMA revealed loss of integrity of the NADPH oxidase at 2 and 3 days following CPB. Conclusions. A vulnerable window exists between 3 and 12 h after CPB when P MNs are primed for enhanced cytotoxicity via O-2(-) production and elastase release. Paradoxically, PMN oxidase integrity becomes deficient 48 h post- CPB, while protease degranulation remains intact. These events render the b ypass patient at risk for multiple organ failure via both early PMN-mediate d tissue injury and delayed infectious complications. (C) 1999 Academic Pre ss.