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Cited by 82Cardiac and Coronary Surgery TechniquesNeutrophil, Myeloperoxidase and Oxidative MechanismsInflammation biomarkers and pathways

Cardiopulmonary Bypass Renders Patients at Risk for Multiple Organ Failure via Early Neutrophil Priming and Late Neutrophil Disability

Partrick, David A., Moore, Ernest E., Fullerton, David A., Barnett, Carlton C., Meldrum, Daniel R., Silliman, Christopher C.·1999·Journal of Surgical Research
DOI 10.1006/jsre.1999.5702
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Abstract

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).Materials and 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.

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Crossref · 10.1006/jsre.1999.5702

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  • Although no patients developed organ failure, the data suggests that these patients' PMNs levels increased early following CPB, and therefore according to the two-hit model of MOF, were rendered vulnerable to end-organ dysfunction from such insults as post-operative bleeding or infection.

    “Although in the present study no patients developed organ failure, the data suggests that these patients’ PMNs levels increased early following CPB, and therefore according to the two-hit model of MOF [10,39], were rendered vulnerable to end-organ dysfunction from such insults as post-operative bleeding or infection.”

    From Oral neutrophils are an independent marker of the systemic inflammatory response after cardiac bypass (2014) · cites this paper as [10]

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Authors
Partrick, D. A., Moore, E. E., Fullerton, D. A., Barnett, C. C., Meldrum, D. R., & Silliman, C. C.
Affiliations
  • Denver Health Medical Center (US)
  • Northwestern University (US)
ORCID
Venue
Journal of Surgical Research
Publisher
Elsevier BV
Published
1999-09
Volume
86
Issue
1
Pages
42-49
ISSN
0022-4804 (ISSN-L)
DOI
10.1006/jsre.1999.5702
OpenAlex
W2052892308
Cited by
82
References
40
Citations by year
2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 3
FWCI
4.91
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Surgical Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of General Medical Sciences (P50-GM49222, T32GM08315, P50GM049222, T32GM008315)
  • National Center for Research Resources (M01 RR00069, M01RR000069)
Topics
  • Health Sciences › Medicine › Surgery › Cardiac and Coronary Surgery Techniques
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
cardiopulmonary bypass, neutrophil priming, neutrophil dysfunction, multiple organ failure, systemic inflammatory response syndrome, superoxide production, NADPH oxidase, neutrophil elastase release, prostaglandin A2, C5a, coronary artery bypass grafting, postoperative infection, neutrophil-mediated tissue injury
MeSH terms
Adolescent, Adult, Aged, Cardiopulmonary Bypass, Female, Humans, Male, Middle Aged, Multiple Organ Failure, Neutrophils, Pancreatic Elastase, Platelet Activating Factor, Risk Factors, Tetradecanoylphorbol Acetate, Time Factors, Reactive Oxygen Species, NADPH Oxidases

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