Cardiopulmonary bypass renders patients at risk for multiple organ failure via early neutrophil priming and late neutrophil disability.
BACKGROUND
Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response syndrome (SIRS) and these patients are recognized to be at increased risk for delayed infectious complications. We have documented that circulating neutrophils (PMNs) from patients manifesting SIRS have evidence of early postinjury priming for cytotoxicity. Consequently, we hypothesized that CPB would result in early postoperative PMN hyperresponsiveness (priming).


METHODS
Six patients (mean age 50 +/- 2.9 years) who underwent 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 to fMLP, C5a, or PMA; elastase release (% total PMN elastase content) was measured by cleavage of AAPV-pNA after exposure to fMLP or C5a.


RESULTS
PMNs were activated for increased elastase release 6 h after initiation 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 than that of the preoperative control. Neutrophil primability with PAF was detected 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 PMNs 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 bypass patient at risk for multiple organ failure via both early PMN-mediated tissue injury and delayed infectious complications.
Partrick
D A
DA
Department of Surgery, Denver Health Medical Center, Denver, Colorado 80204, USA.
Moore
E E
EE
Fullerton
D A
DA
Barnett
C C
CC
Meldrum
D R
DR
Silliman
C C
CC
D000293:Adolescent; D000328:Adult; D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology*; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D010196:Pancreatic Elastase; D013755:Tetradecanoylphorbol Acetate