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

Axel Nyberg,Miklós Lipcsey,Mikko Hurme,Jesper Sperber,Juulia Jylhävä,Markus Castegren,Alexander Larsson

doi:10.1186/s12890-020-01239-y

Abstract

BackgroundPlasma 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.MethodOne 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.ResultsThe 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.ConclusionsProtective 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.

Highlights

Plasma levels of cell-free DNA are known to be elevated in sepsis and high levels are associated with a poor prognosis
The liver seems to be a net contributor to the systemic cell-free DNA (cf-DNA) levels, but this effect is attenuated by protective ventilation
In the animals allocated to group Prot-V after baseline, the levels of cf-DNA in the artery, hepatic vein, portal vein and jugular bulb did not differ between the animals that were ventilated with a Tidal volume (VT) of 10 mL x kg− 1 and those with 6 mL x kg− 1 during the preparatory phase of the experiment, Table 1

Summary

Introduction

Plasma levels of cell-free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Over the past decades, increased levels of cfDNA have been detected in the plasma of patients with diseases e.g., cancer [1], trauma [3], stroke [4], myocardial infarction [5, 6], post-cardiac arrest [7], and pancreatitis [8], with higher levels associated with worse outcome. Several other studies have demonstrated higher levels of cf-DNA in non-survivors compared with survivors in sepsis, and septic shock [2, 10,11,12,13]. This view has recently been challenged [14]

Results

Discussion

Conclusion