Cell-Free Circulating Mitochondrial DNA Levels Following High-Frequency Jet Ventilation-A Post Hoc Analysis

Background: Mitochondrial DNA (mtDNA), normally enclosed within mitochondria, can be released into circulation in response to cellular stress, hypoxia, or inflammation. Its detection in plasma has been proposed as a marker of cellular injury, particularly in the context of mechanical ventilation. High-frequency jet ventilation is a specialized approach of open-airway ventilation, delivering small tidal volumes through jet gas streams, applied with high pressure and oxygen fraction. It remains unclear whether this mode of ventilation contributes to mitochondrial stress. We therefore hypothesized that circulating mtDNA levels would increase after jet ventilation due to the combined effects of high oxygen exposure and mechanical strain. Furthermore, we explored whether the magnitude of mtDNA change correlates with the duration of ventilation and arterial oxygenation levels. Methods: Plasma levels of cell-free circulating mitochondrial DNA were measured in 30 patients before and following jet ventilation in laryngotracheal surgery. Post hoc analysis of a primary monocentric, randomized cross-over study was conducted to investigate ventilation distribution in high-frequency jet ventilation techniques. Results: Mitochondrial DNA levels significantly decreased after jet ventilation (median T0: 13.57; T1: 6.78; p = 0.0087). No significant associations were found between mtDNA change and jet ventilation duration, type of surgery, or ASA classification. Despite variable air entrainment in the open-jet ventilation system, the arterial partial pressure of oxygen increased significantly during the procedure. Conclusions: Jet ventilation was associated with a significant decrease in circulating mtDNA levels. This contrasts with our initial hypothesis of mtDNA elevation under ventilation-induced stress. These findings suggest that jet ventilation may exert less mitochondrial damage than previously expected.