Hyperbaric Oxygen Therapy (HBOT) allows individuals to inhale 100% oxygen under pressures exceeding one atmosphere absolute (1 ATA). This elevates the amount of oxygen dissolved in body tissues. While historically, HBOT was predominantly used for treating chronic non-healing wounds, its application has seen a paradigm shift.

Emerging evidence underscores HBOT’s regenerative capabilities. The synergetic effects of hyperoxia and hyperbaric pressure significantly enhance tissue oxygenation. This process activates oxygen and pressure-sensitive genes, bolstering mitochondrial metabolism while offering anti-apoptotic and anti-inflammatory benefits. Impressively, these genes also stimulate stem cell proliferation and elevate the levels of endothelial progenitor cells (EPCs) and angiogenesis factors, fostering improved blood flow in ischemic areas. Recent studies further suggest HBOT’s potential in promoting brain regeneration and neuroplasticity.

A striking observation is the Hyperoxic-Hypoxic Paradox, where the intermittent oxygen surge mimics several cellular mechanisms typically associated with hypoxia, but without its detrimental effects. Such HHP exposures influence HIF-1 levels, matrix metalloproteinases (MMP) activity, and VEGF. Besides promoting angiogenesis, HBOT tempers the inflammatory response in endothelial cells, as evidenced by reduced TNF-alpha mediation, thus catalyzing vascular recovery. Comprehensive animal and human studies have illuminated HBOT’s positive impact on mitochondrial functionality and associated metabolism.

In this lecture, we aim to elucidate the physiological intricacies of the “Hyperoxic-Hypoxic Paradox” and shed light on the accumulating data concerning brain injuries, age-associated functional decline, and cardio-muscular performance.

Learning Objectives:

1. Examine the proven benefits of specific protocols of hyperbaric oxygen therapy in inducing the “Hyperoxic-Hypoxic Paradox” (HHP).
2. Investigate the cellular-level biological cascades triggered by the Hyperoxic-Hypoxic Paradox.
3. Investigate the physiological effects at both tissue and whole-body levels brought about by the Hyperoxic-Hypoxic Paradox.
4. Discuss various patient groups (those experiencing age-related cognitive decline, stroke, traumatic brain injury, Long-COVID) who can benefit from HHP.
5. Develop the proficiency to effectively evaluate and set patient expectations regarding HHP treatment.