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Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis

BACKGROUND: Plasma levels of cell-free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Mechanical ventilation affects systemic inflammation in which lung-protective ventilation attenuates the inflammatory response. The aim was to study the effect...

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Autores principales: Nyberg, Axel, Larsson, Alexander, Jylhävä, Juulia, Hurme, Mikko, Sperber, Jesper, Lipcsey, Miklós, Castegren, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393331/
https://www.ncbi.nlm.nih.gov/pubmed/32736620
http://dx.doi.org/10.1186/s12890-020-01239-y
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author Nyberg, Axel
Larsson, Alexander
Jylhävä, Juulia
Hurme, Mikko
Sperber, Jesper
Lipcsey, Miklós
Castegren, Markus
author_facet Nyberg, Axel
Larsson, Alexander
Jylhävä, Juulia
Hurme, Mikko
Sperber, Jesper
Lipcsey, Miklós
Castegren, Markus
author_sort Nyberg, Axel
collection PubMed
description BACKGROUND: Plasma levels of cell-free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Mechanical ventilation affects systemic inflammation in which lung-protective ventilation attenuates the inflammatory response. The aim was to study the effect of a lung protective ventilator regime on arterial and organ-specific venous blood as well as on trans-organ differences in cf-DNA levels in a porcine post-operative sepsis model. METHOD: One group of anaesthetised, domestic-breed, 9–12 weeks old, pigs were ventilated with protective ventilation (V(T) 6 mL x kg(− 1), PEEP 10 cmH(2)O) n = 20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (V(T) 10 mL x kg(− 1), PEEP 5 cm H(2)O) n = 10. Blood samples were taken from four sources: artery, hepatic vein, portal vein and, jugular bulb. A continuous endotoxin infusion at 0.25 μg x kg(− 1) x h(− 1) for 5 h was started following 2 h of laparotomy, which simulated a surgical procedure. Inflammatory cytokines and cf-DNA in plasma were analysed and trans-organ differences calculated. RESULTS: The protective ventilation group had lower levels of cf-DNA in arterial (p = 0.02) and hepatic venous blood (p = 0.03) compared with the controls. Transhepatic differences in cf-DNA were lower in the protective group, compared with the controls (p = 0.03). No differences between the groups were noted as regards the transcerebral, transsplanchnic or the transpulmonary cf-DNA differences. CONCLUSIONS: Protective ventilation suppresses arterial levels of cf-DNA. The liver seems to be a net contributor to the systemic cf-DNA levels, but this effect is attenuated by protective ventilation.
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spelling pubmed-73933312020-07-31 Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis Nyberg, Axel Larsson, Alexander Jylhävä, Juulia Hurme, Mikko Sperber, Jesper Lipcsey, Miklós Castegren, Markus BMC Pulm Med Research Article BACKGROUND: Plasma levels of cell-free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Mechanical ventilation affects systemic inflammation in which lung-protective ventilation attenuates the inflammatory response. The aim was to study the effect of a lung protective ventilator regime on arterial and organ-specific venous blood as well as on trans-organ differences in cf-DNA levels in a porcine post-operative sepsis model. METHOD: One group of anaesthetised, domestic-breed, 9–12 weeks old, pigs were ventilated with protective ventilation (V(T) 6 mL x kg(− 1), PEEP 10 cmH(2)O) n = 20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (V(T) 10 mL x kg(− 1), PEEP 5 cm H(2)O) n = 10. Blood samples were taken from four sources: artery, hepatic vein, portal vein and, jugular bulb. A continuous endotoxin infusion at 0.25 μg x kg(− 1) x h(− 1) for 5 h was started following 2 h of laparotomy, which simulated a surgical procedure. Inflammatory cytokines and cf-DNA in plasma were analysed and trans-organ differences calculated. RESULTS: The protective ventilation group had lower levels of cf-DNA in arterial (p = 0.02) and hepatic venous blood (p = 0.03) compared with the controls. Transhepatic differences in cf-DNA were lower in the protective group, compared with the controls (p = 0.03). No differences between the groups were noted as regards the transcerebral, transsplanchnic or the transpulmonary cf-DNA differences. CONCLUSIONS: Protective ventilation suppresses arterial levels of cf-DNA. The liver seems to be a net contributor to the systemic cf-DNA levels, but this effect is attenuated by protective ventilation. BioMed Central 2020-07-31 /pmc/articles/PMC7393331/ /pubmed/32736620 http://dx.doi.org/10.1186/s12890-020-01239-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Nyberg, Axel
Larsson, Alexander
Jylhävä, Juulia
Hurme, Mikko
Sperber, Jesper
Lipcsey, Miklós
Castegren, Markus
Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis
title Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis
title_full Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis
title_fullStr Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis
title_full_unstemmed Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis
title_short Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis
title_sort lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free dna in porcine experimental post-operative sepsis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393331/
https://www.ncbi.nlm.nih.gov/pubmed/32736620
http://dx.doi.org/10.1186/s12890-020-01239-y
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