Hyperbaric Oxygen-Induced acute lung injury: A Mouse Model Study on Pathogenesis and Recovery Dynamics

Abstract

Hyperbaric oxygen (HBO) therapy is extensively used to treat a number of ailments. Although oxygen is crucial for survival, too much oxygen can be harmful. Excessive oxygen inhalation in a short period of time can lead to injury, and the lung is one of the main target organs. Lung injury induced by hyperbaric oxygen is notably more severe than that caused by normobaric oxygen, yet systematic research on such injury and its regression is scarce. In this study, mice were exposed to 2 atmospheres absolute (ATA), [>=] 95% oxygen for 2, 4, 6, 8 hours. Changes in lung histopathology, inflammation and expression of chemokines, vascular endothelial permeability, 8-OHdG and apoptotic cells were detected before and after the exposure. These parameters were also measured immediately, 12 hours, and 24 hours following 6 hours of exposure to 2 ATA of [>=]95% oxygen. The study indicates that lung damage from HBO is histologically characterized by bronchiolar and alveolar dilation, atelectasis, inflammatory cell infiltration, and hemorrhage. At 2 ATA with over 95% oxygen for 4 hours, there is a significant increase in pulmonary vascular permeability, as evidenced by elevated Evans blue scores (p = 0.02). After 6 hours of HBO exposure, there is a significant rise in pulmonary tissue pathology scores, 8-OHdG levels, and inflammatory and chemotactic factors (such as IL-6, CCL2, CCL3, CXCL5, and CXCL10), along with intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1(VCAM1). Moreover, it was observed that these markers continued to progress even after leaving the hyperoxic environment, peaking at 12 hours and starting to recover after 24 hours, suggesting that the peak of inflammatory lung damage occurs within 12 hours post-exposure, with recovery beginning at 24 hours. However, the content of Evans Blue, reflecting vascular endothelial damage, and ICAM1, VCAM1 remain significantly elevated 24 hours after leaving the hyperoxic environment, indicating that the pulmonary vasculature endothelium is the most sensitive to damage and the slowest to recover in HBO-induced lung injury. These findings provide evidence for the prevention and treatment of acute lung injury complications caused by HBO. NEW & NOTEWORTHYThis study systematically observed the development and outcome changes of ALI induced by HBO. In lung injuries caused by high partial pressure of oxygen, the pulmonary vascular endothelial cells are the first to be damaged and the slowest to recover. A 6-hour exposure to 2 ATA, [>=]95% oxygen of hyperbaric oxygen primarily causes oxidative DNA damage and inflammatory responses without significant apoptosis. The lung injury progresses even after leaving the high-oxygen setting, with inflammation peaking at 12 hours post-exposure and beginning to subside after 24 hours.