Department of Anesthesiology, Centre of Head and Orthopedics, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
Biomolecules. 2023 Aug 7;13(8):1228. doi: 10.3390/biom13081228.
The perception of sepsis has shifted over time; however, it remains a leading cause of death worldwide. Sepsis is now recognized as an imbalance in host cellular functions triggered by the invading pathogens, both related to immune cells, endothelial function, glucose and oxygen metabolism, tissue repair and restoration. Many of these key mechanisms in sepsis are also targets of hyperbaric oxygen (HBO) treatment. HBO treatment has been shown to improve survival in clinical studies on patients with necrotizing soft tissue infections as well as experimental sepsis models. High tissue oxygen tension during HBO treatment may affect oxidative phosphorylation in mitochondria. Oxygen is converted to energy, and, as a natural byproduct, reactive oxygen species are produced. Reactive oxygen species can act as mediators, and both these and the HBO-mediated increase in oxygen supply have the potential to influence the cellular processes involved in sepsis. The pathophysiology of sepsis can be explained comprehensively through resistance and tolerance to infection. We argue that HBO treatment may protect the host from collateral tissue damage during resistance by reducing neutrophil extracellular traps, inhibiting neutrophil adhesion to vascular endothelium, reducing proinflammatory cytokines, and halting the Warburg effect, while also assisting the host in tolerance to infection by reducing iron-mediated injury and upregulating anti-inflammatory measures. Finally, we show how inflammation and oxygen-sensing pathways are connected on the cellular level in a self-reinforcing and detrimental manner in inflammatory conditions, and with support from a substantial body of studies from the literature, we conclude by demonstrating that HBO treatment can intervene to maintain homeostasis.
脓毒症的概念随着时间的推移而发生了变化；然而，它仍然是全球范围内导致死亡的主要原因之一。现在，脓毒症被认为是宿主细胞功能失衡的一种表现，这种失衡是由入侵病原体触发的，与免疫细胞、内皮功能、葡萄糖和氧代谢、组织修复和恢复等都有关系。在脓毒症中，许多这些关键机制也是高压氧（HBO）治疗的靶点。临床研究表明，HBO 治疗可提高坏死性软组织感染和实验性脓毒症模型患者的生存率。在 HBO 治疗期间，高组织氧张力可能会影响线粒体中的氧化磷酸化。氧被转化为能量，作为一种天然副产物，产生活性氧物质。活性氧物质可以作为介质，而这些物质以及 HBO 介导的氧供应增加都有可能影响脓毒症涉及的细胞过程。通过对感染的抵抗力和耐受性，可以全面解释脓毒症的病理生理学。我们认为，HBO 治疗可以通过减少中性粒细胞胞外陷阱、抑制中性粒细胞黏附于血管内皮、减少促炎细胞因子以及阻止瓦伯格效应，从而减少组织损伤，在抵抗阶段保护宿主免受继发组织损伤，同时通过减少铁介导的损伤和上调抗炎措施来帮助宿主耐受感染。最后，我们展示了在炎症条件下，炎症和氧感应途径在细胞水平上是如何以自我强化和有害的方式相互联系的，并且在大量文献研究的支持下，我们得出结论，HBO 治疗可以干预以维持体内平衡。
