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. 2020 Jul 31;20(1):206.
doi: 10.1186/s12890-020-01239-y.

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

Axel Nyberg  1   2 , Alexander Larsson  3 , Juulia Jylhävä  4 , Mikko Hurme  5 , Jesper Sperber  6   7 , Miklós Lipcsey  8 , Markus Castegren  7   9
Affiliations

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

Axel Nyberg et al. BMC Pulm Med. .

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.

Keywords: Cytokines; Endotoxin; Innate immunity; Intensive care; Low tidal volume ventilation.

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Conflict of interest statement

All co-authors state that they have no competing interests.

Figures

Fig. 1
Fig. 1
Design of the study
Fig. 2
Fig. 2
Plasma concentrations of cell free DNA (cf-DNA) in different sampling sites. Values are mean ± SE. The p-value is the results of group effect in the analysis of variance (ANOVA) for repeated measures
Fig. 3
Fig. 3
Plasma concentrations of cell free DNA (cf-DNA) by groups. a. arterial b. hepatic vein c. portal vein d. jugular bulb. Values are given as mean ± SE. P-values are based on the results of group effect in the analysis of variance (ANOVA) for repeated measures
Fig. 4
Fig. 4
Trans-organ differences in cell free DNA (cf-DNA). Values are given as mean ± SE. P-values are based on the results of the group effect in the analysis of variance (ANOVA) for repeated measures. Transpulmonary: the difference in plasma levels between the artery and the hepatic vein, transhepatic: the difference between the hepatic vein and the portal vein, transsplanchnic: the difference between the portal vein and the artery, transcerebral: the difference between the jugular bulb and the artery
Fig. 5
Fig. 5
Change from baseline at 0 h (%) in trans-organ differences in cell free DNA (cf-DNA) by groups. a. transhepatic b. transcerebral c. transsplanchnic d. transpulmonary. Values are given as mean ± SE. P-values are based on the results of the group effect in the analysis of variance (ANOVA) for repeated measures. Transpulmonary: the difference in plasma levels between the artery and the hepatic vein, transhepatic: the difference between the hepatic vein and the portal vein, transsplanchnic: the difference between the portal vein and the artery, transcerebral: the difference between the jugular bulb and the artery
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