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Enhanced growth of Staphylococcus aureus after nitric oxide supplementation during simulated extracorporeal circulation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.ORCID iD: 0000-0002-3631-2589
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2010 (English)In: The thoracic and cardiovascular surgeon, ISSN 0171-6425, E-ISSN 1439-1902, Vol. 58, no 2, 81-85 p.Article in journal (Refereed) Published
Abstract [en]

Background: Several factors contribute to postoperative bacterial infections in cardiac surgery. Long operation times and the use of extracorporeal circulation increase the risk of infection. Nitric oxide has been shown to possess a broad spectrum antimicrobial effect. Methods: In this study, we investigated the effect of nitric oxide on S. aureus growth in whole blood during simulated extracorporeal circulation. Results: S. aureus growth increased 6.2-fold after 180 min SECC in the presence of nitric oxide. Leukocyte counts remained unchanged without any differences between the groups. We observed a steady increase in markers of oxidative stress and activity of the innate immune system. Myeloperoxidase levels increased 8-fold, and C3a and terminal complement complex by 2-fold after 180 min. Conclusion: S. aureus growth is not due to the effect of nitric oxide on the innate immune system but from its effect on the bacteria itself. It has been shown that nitric oxide stimulates the expression of inducible lactate dehydrogenase, specific to S. aureus, which improves its resistance to oxidative stress, and may give S. aureus a survival advantage resulting in increased growth.

Place, publisher, year, edition, pages
2010. Vol. 58, no 2, 81-85 p.
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-298778DOI: 10.1055/s-0029-1186135OAI: oai:DiVA.org:uu-298778DiVA: diva2:947300
Available from: 2016-07-07 Created: 2016-07-07 Last updated: 2017-05-18Bibliographically approved
In thesis
1. Nitric oxide: An ally in extracorporeal circulation?
Open this publication in new window or tab >>Nitric oxide: An ally in extracorporeal circulation?
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Many complications associated with heart surgery are due to the negative effects of extracorporeal circulation (ECC). Some of these complications may be attributed to ECC-induced activation of inflammation and coagulation pathways. The inflammatory reaction may be caused by the interaction of blood components with air and the artificial surfaces of the ECC, from substances produced due to ischaemia-reperfusion injury of the heart and lungs, and from increased release of endotoxin from ischemic intestines. Staphylococcus aureus (S. aureus) infections are the leading cause of respiratory, skin and soft tissue, and bloodstream infections. Nitric oxide (NO) is a gaseous signaling molecule involved in many physiological and pathological processes. The role of NO in infection and inflammation is complex. NO may contribute to morbidity by acting as a vasodilator, myocardial depressant, and cytotoxic mediator. On the other hand, NO may have a salutary role through microvascular, cytoprotective, immunoregulatory, and antimicrobial properties. A simulated extracorporeal circulation (SECC) model is a closed circuit, including a roller pump, an oxygenator, a venous reservoir and polyvinyl chloride (PVC) tubing, where human blood is circulated. The SECC model allows studies of the blood and its components, without any influence from other organ systems. The aim of this work was to investigate NO effects during SECC and in S. aureus infection.

Study I. Human blood was circulated through SECC during 3 hours, and leukocyte granule release was studied. Results indicated that NO addition during SECC is pro-inflammatory by stimulating leukocyte activation and granule release, and has no effect on oxygen free radical production and interleukin release.

Study II. Investigating the effect of NO on S. aureus growth in whole blood during 180 min SECC, results showed a 6.2 fold growth in the presence of NO. Results indicated that by stimulating the expression of inducible lactate dehydrogenase, specific to S. aureus, NO may improve S. aureus resistance to oxidative stress, giving the pathogen a survival advantage.

Study III. In an in vitro system of SECC, we measured glyceryl trinitrate (GTN) induced changes in leukocyte activation in whole blood caused by S. aureus infestation, as well as the effect of GTN on S. aureus growth. Results indicated that GTN does not affect S. aureus growth during SECC and has no effect on SECC-induced leukocyte activation.

Study IV. Whole blood concentrations of selected leukocyte adhesion molecules, complement system components and myeloperoxidase  were measured in an in vitro system of SECC. Results indicated that SECC induces the increased expression of some leukocyte markers and that GTN addition significantly reduces the expression of some leukocyte activation markers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 81 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1238
Keyword
Simulated extracorporeal circulation, Inflammation, Nitric oxide, Leukocyte activation, Staphylococcus aureus, Glyceryl trinitrate, Postoperative infection
National Category
Surgery
Research subject
Thorax Surgery
Identifiers
urn:nbn:se:uu:diva-298782 (URN)978-91-554-9626-5 (ISBN)
Public defence
2016-09-15, Gunnesalen, Ingång 10, Uppsala Akademiska Sjukhus, 751 85, Uppsala, 12:00 (English)
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Supervisors
Available from: 2016-08-25 Created: 2016-07-07 Last updated: 2016-10-14

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Melki, VilyamTano, EvaKnutson, FolkeBorowiec, Jan W.
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