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Dynamics of leucocytes correlate with increased pulmonary vascular permeability and decreased PaO2:FiO2 ratio early after major burns
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
Lund University, Department Clin Science, Div Infect Med, Lund, Sweden .
Karolinska Institute, Department Physiol and Pharmacol, Stockholm, Sweden .
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2009 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: The lung is affected soon after a major burn as indicated by a decreased PaO2:FiO2 ratio. The exact mechanism underlying this is not known. Polymorphonuclear leucocytes (PMN) are activated systemically and their numbers are largely increased soon after a burn followed by a rapid decline to low normal or subnormal numbers within 24 hours, possibly by increased extravasation. Experimental data have supported the hypothesis that an important target for this extravasation is the lungs. Other studies also show that when PMN adhere to endothelial cells they increase vascular permeability, and this effect is mediated, at least in part, by release of heparin binding protein (HBP, also known as CAP-37 and azurocidin). We hypothesised that there is a relation between early increased pulmonary vascular permeability or a decreased PaO2:FiO2 ratio and the dynamic change in blood leucocytes after a burn, possibly mediated by the local release of HBP.

Material and methods: This is a prospective, descriptive, exploratory, singlecentre study at a national burn centre. We investigated the dynamic changes of leucocytes in blood, plasma concentrations of HBP, pulmonary vascular permeability index (PVPI) by thermodilution, and PaO2:FiO2 ratios in 20 patients during the first 21 days after a major burn (20% >total burn surface area %).

Results: Median total burn surface area was 40% (IQR 25-52) and full thickness burn 28% (IQR 2-39). There was a correlation between the early (<24 hours) alteration in circulating white blood cell count and both early increased vascular permeability in the lung (r=0.63, p=0.004) and the decreased oxygenation index defined as PaO2:FiO2 < 27 kPa (p=0.004). There were no associations between plasma concentrations of HBP and measured pulmonary vascular permeability or PaO2:FiO2 ratios.

Conclusions: The results indicate that trapping of leucocytes in the lung may be an important factor in early increased pulmonary vascular permeability and decrease of the PaO2:FiO2 ratio. Our data do not support the idea that HBP, assessed by systemic plasma concentrations, mediate this effect.

Place, publisher, year, edition, pages
2009.
Keyword [en]
ARDS, azurocidin, burn, CAP-37, HBP, leukocyte, mediator, permeability, PMN, trauma
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-94511OAI: oai:DiVA.org:liu-94511DiVA: diva2:632563
Available from: 2013-06-25 Created: 2013-06-25 Last updated: 2013-06-25Bibliographically approved
In thesis
1. Function of granulocytes after burns and trauma, associations with pulmonary vascular permeability, acute respiratory distress syndrome, and immunomodulation
Open this publication in new window or tab >>Function of granulocytes after burns and trauma, associations with pulmonary vascular permeability, acute respiratory distress syndrome, and immunomodulation
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Our innate immunesystem protects us from infections but, since its methods is not all specific for microorganisms, may also induce collateral damage.

Severe physical injury often proved deadly throughout evolution. Such injuries may induce massive collateral damage. Nowadays we can initiate advanced critical care for affected patients and save them from imminent trauma-related death. We are therefore faced with the fact that the collateral damage from the immune system may pose a major threat to the patient, the pathophysiology of which is not amenable to direct medical treatment and which leaves us with only passive supportive measures.

In this thesis we investigated the role of leucocytes under such circumstances.

Our main aim was to understand better the role of leucocytes in the development of increased vascular permeability after burns and trauma.

More specifically we investigated the impact of an injury on the function of leucocytes such as the dynamic change of certain cell-surface receptors on the leucocytes and in their numbers and immature forms. We wanted to find out if the increased pulmonary vascular permeability after a burn could be mediated through heparin binding protein (HBP) released from granuloctes, and whether HBP could be used as a biomarker for respiratory failure after trauma. We also wanted to confirm the possible role of histamine as a mediator of the systemic increase in vascular permeability after burns.

Methods: The dynamic change of cell-surface receptors was measured by flow-acquired cytometer scanning (FACS) on blood samples taken after burns. The concentrations of HBP after a burn and mechanical trauma were analysed in plasma. Pulmonary vascular permeability after a burn was assessed using transpulmonary thermodilution. The histamine turnover after a burn was assessed with high performance liquid chromatography (HPLC) for concentrations of histamine and methylhistamine in urine.

Results: We confirmed earlier investigations showing altered expression of receptors on leucocytes after a burn, receptors intimately associated with leucocyte functions (study I). In a pilot study of 10 patients we measured plasma concentrations of HBP and found them to be increased soon after a burn (study II). This finding was not confirmed in a larger, more extensive and specific study of 20 patients. We did, however, find an association between alterations in the number of leucocytes soon after a burn and pulmonary vascular permeability, indicating that they had a role in this process (study III).

In another study of trauma (non burn) we found an association between the concentration of HBP in early plasma-samples after injury and the development of ARDS, indicating that granulocytes and HBP have a role in its aetiology (study IV).

We found a small increase in urinary histamine and normal urinary methylhistamine concentrations but had anticipated a distinct increase followed by a decrease after reading the current papers on the subject. This indicates that the role of histamine as a mediator of increased vascular permeability after burns may have been exaggerated (study V).

Conclusions: We conclude that leucocytes are affected by burns and trauma, and it is likely that they contribute to the development of respiratory failure and acute respiratory distress syndrome (ARDS). HBP is a candidate biomarker for the early detection of ARDS after trauma, and the white blood count (WBC) is a useful biomarker for the detection of decreased oxygenation soon after a burn.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1362
Keyword
ARDS, azurocidin, burn, CAP-37, critical care, granulocyte, HBP, histamine, intensive care, leucocyte, leukocyte, mediator, methylhistamine, MOF, oedema, neutrophil, permeability, PMN, trauma, vascular permeability
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-94513 (URN)978-91-7519-632-9 (ISBN)
Public defence
2013-09-05, Elsa Brändström salen, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
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Supervisors
Available from: 2013-06-25 Created: 2013-06-25 Last updated: 2014-03-24Bibliographically approved

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Johansson, JoakimSteinvall, IngridSjoberg, Folke

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Department of Medical and Health SciencesFaculty of Health SciencesDepartment of Clinical and Experimental MedicineDepartment of Plastic Surgery, Hand surgery UHLBurn CenterDepartment of Plastic Surgery, Hand surgery UHL
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