Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis
Abstract 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 th...
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | BMC Pulmonary Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12890-020-01239-y |
| _version_ | 1818942358530555904 |
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| author | Axel Nyberg Alexander Larsson Juulia Jylhävä Mikko Hurme Jesper Sperber Miklós Lipcsey Markus Castegren |
| author_facet | Axel Nyberg Alexander Larsson Juulia Jylhävä Mikko Hurme Jesper Sperber Miklós Lipcsey Markus Castegren |
| author_sort | Axel Nyberg |
| collection | DOAJ |
| description | Abstract 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 (VT 6 mL x kg− 1, PEEP 10 cmH2O) n = 20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (VT 10 mL x kg− 1, PEEP 5 cm H2O) 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. |
| first_indexed | 2024-12-20T07:10:10Z |
| format | Article |
| id | doaj.art-875b7116e79646e986deb1e81c73764f |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-12-20T07:10:10Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-875b7116e79646e986deb1e81c73764f2022-12-21T19:48:54ZengBMCBMC Pulmonary Medicine1471-24662020-07-0120111210.1186/s12890-020-01239-yLung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsisAxel Nyberg0Alexander Larsson1Juulia Jylhävä2Mikko Hurme3Jesper Sperber4Miklós Lipcsey5Markus Castegren6Department of Anaesthesiology & Intensive Care, Centre for Clinical Research, Sörmland, Uppsala UniversityCentre for Clinical Research, Region of Västmanland, Uppsala UniversityDepartment of Medical Epidemiology and Biostatistics, Karolinska InstituteFaculty of Medicine and Health Technology, Tampere UniversityDepartment of Anaesthesiology & Intensive Care, Centre for Clinical Research, Sörmland, Uppsala UniversityHedenstierna laboratory, CIRRUS, Anesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala UniversityDepartment of Medical Sciences, Uppsala UniversityAbstract 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 (VT 6 mL x kg− 1, PEEP 10 cmH2O) n = 20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (VT 10 mL x kg− 1, PEEP 5 cm H2O) 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.http://link.springer.com/article/10.1186/s12890-020-01239-yInnate immunityCytokinesEndotoxinLow tidal volume ventilationIntensive care |
| spellingShingle | Axel Nyberg Alexander Larsson Juulia Jylhävä Mikko Hurme Jesper Sperber Miklós Lipcsey Markus Castegren Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis BMC Pulmonary Medicine Innate immunity Cytokines Endotoxin Low tidal volume ventilation Intensive care |
| 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 | Innate immunity Cytokines Endotoxin Low tidal volume ventilation Intensive care |
| url | http://link.springer.com/article/10.1186/s12890-020-01239-y |
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