A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities

Abstract

Hyperbaric oxygen therapy (HBOT) consists of using of pure oxygen at increased pressure (in general, 2-3 atmospheres) leading to augmented oxygen levels in the blood (Hyperoxemia) and tissue (Hyperoxia). The increased pressure and oxygen bioavailability might be related to a plethora of applications, particularly in hypoxic regions, also exerting antimicrobial, immunomodulatory and angiogenic properties, among others. In this review, we will discuss in detail the physiological relevance of oxygen and the therapeutical basis of HBOT, collecting current indications and underlying mechanisms. Furthermore, potential areas of research will also be examined, including inflammatory and systemic maladies, COVID-19 and cancer. Finally, the adverse effects and contraindications associated with this therapy and future directions of research will be considered. Overall, we encourage further research in this field to extend the possible uses of this procedure. The inclusion of HBOT in future clinical research could be an additional support in the clinical management of multiple pathologies.

Keywords: Coronavirus Disease-19 (COVID-19); Hyperoxia; antimicrobial properties; hyperbaric oxygen therapy (HBOT); wound healing.

Figure 1

Illustration of a monoplace hyperbaric chamber and the effect of hyperbaric O₂. Pressurized O₂ (2–3 atm) at 100% concentration is administered normally during 1.5–2 h per session and repeated three times a day. Depending on the clinical condition sessions vary in number, from 20 to 60. The inhalated air comes from an external elevated PO₂, hence positive gradient allows higher O₂ entry, which per diffusion will be higher also in alveoli, bloodstream and therefore there will be greater arrival to tissues. This effect of “hyperoxemia” and “hyperoxia” is independent from haemoglobin (Hb), then will lessen hypoxia in tissues. This will result in a major supply of reactive oxygen species (ROS) and reactive nitrite species (RNS), with a consequent higher expression of growth factors and promotion of neovascularization and enhanced immunomodulatory properties.

Figure 2

Summary of top properties of HBOT and its clinical applications. Firstly, it can provide an angiogenesis enhancement, observed by the prime production of NO which subsequently brings an upregulation of Nrf2 and growth factors like epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and endothelin-1. TNF-α, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) will be boosted too. Secondly, the antimicrobial activity is visible due to bacterial killing by O₂, removing biofilm and lessening white blood cells (WBCs) rolling and neutrophils recruitment, hence promoting a downregulation of proinflammatory cytokines (TNF-α, IL-6 and IL-10). The immunomodulation properties are observed by a downregulation of transcriptional factor NFkB, involving a proinflammatory response switch off (IL-6) and a polarization from Th17 lymphocytes to Treg. Summarized applications include: indications for which HBOT is approved (mostly wound healing and infections), primary emergencies (like CO/CN poisoning or air embolism), and translational research (comprising COVID-19, cancer, inflammatory conditions or aging among others).