Wefers Bettink Mark A, Zwaag Jelle, Schockaert Bernard, Pickkers Peter, Kox Matthijs, Mik Egbert G
Department of Anesthesiology laboratory of experimental anesthesiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Anesthesiology, Fransiscus Gasthuis and Vlietland Hospital, Rotterdam, The Netherlands.
Sci Rep. 2025 Jul 16;15(1):25815. doi: 10.1038/s41598-025-10715-6.
Disturbances in mitochondrial function are implicated in several chronic and acute diseases. Systemic inflammation has been described to affect mitochondrial respiration. Yet, in vivo measurement of mitochondrial respiration is notoriously difficult. We measured mitochondrial oxygen tension (mitoPO) and mitochondrial oxygen consumption (mitoVO) using the bedside COMET (Cellular Oxygen METabolism) system during systemic inflammation elicited by intravenous administration of 2 ng/kg lipopolysaccharide (LPS) in 42 healthy male volunteers. Four male subjects who did not receive LPS served as uninflamed controls. MitoPO and mitoVO were measured immediately prior to LPS administration, and at 1.45 h, 4 h, and 7 h, as well as at the corresponding timepoints in the control group. Compared to the control group, MitoPO significantly decreased over time in the LPS group (p = 0.002), with the nadir observed at 1.45 h post-LPS administration (45.8 ± 1.8 vs. 75.2 ± 2.6 mmHg); while mitoVO did not change. Concluding, the COMET monitor detects changes in mitochondrial parameters in a relatively mild model of systemic inflammation. This study paves the way for bedside monitoring of alterations in mitochondrial oxygenation and respiration, which may represent a vital next step in early diagnosis of mitochondrial dysfunction and stratification of patients in the intensive care unit.Trial registration: ClinicalTrials.gov NCT03240497. (12/04/2016) toetsingonline.nl NL56686.091.16 (11/04/2016) and NL65767.078.18 (01/05/2018).
线粒体功能紊乱与多种慢性和急性疾病有关。已有研究表明全身炎症会影响线粒体呼吸。然而，在体内测量线粒体呼吸非常困难。我们在42名健康男性志愿者中，通过静脉注射2 ng/kg脂多糖（LPS）引发全身炎症，使用床边COMET（细胞氧代谢）系统测量线粒体氧张力（mitoPO）和线粒体氧消耗（mitoVO）。四名未接受LPS的男性受试者作为未发炎对照。在LPS给药前、给药后1.45小时、4小时和7小时以及对照组的相应时间点测量mitoPO和mitoVO。与对照组相比，LPS组的MitoPO随时间显著降低（p = 0.002），在LPS给药后1.45小时观察到最低点（45.8±1.8 vs. 75.2±2.6 mmHg）；而mitoVO没有变化。总之，COMET监测仪在相对轻度的全身炎症模型中检测到线粒体参数的变化。本研究为床边监测线粒体氧合和呼吸的改变铺平了道路，这可能是线粒体功能障碍早期诊断和重症监护病房患者分层的关键下一步。试验注册：ClinicalTrials.gov NCT03240497（2016年4月12日）；toetsingonline.nl NL56686.091.16（2016年4月11日）和NL65767.078.18（2018年5月1日）。
