Hyperbaric oxygen therapy: A comprehensive guide to therapeutic applications and mechanisms

Fundamentals and history of hyperbaric oxygen therapy

The first documented use of hyperbaric medical therapy dates back to 1662, when British physician Henshaw pioneered treatment by placing patients in a pressurized air container. This predated both the formulation of Boyle-Mariotte Law, describing pressure-volume gas relationships, and oxygen's discovery by Priestley over a century later.

A significant advancement came from Paul Bert, considered the "father of hyperbaric physiology", who in 1872 described physiological effects of pressurized air on the human body. He also defined oxygen's neurotoxic effects, now known as the Paul Bert effect. Lorrain Smith later documented pulmonary oxygen toxicity.

Modern HBOT operates through two key physical principles:

• Henry's Law: The amount of dissolved gas in a liquid is directly proportional to its partial pressure
• Boyle-Mariotte Law: Pressure and gas volume have an inverse relationship

Treatment is delivered in either monoplace chambers (single patient, compressed with pure oxygen) or multiplace chambers (multiple patients breathing oxygen through masks). Standard protocols typically involve 90-120 minute sessions at 2-3 atmospheres absolute (ATA) pressure, with frequency varying by condition.

HBOT gained widespread medical recognition during World War II for treating decompression sickness in divers. By the early 21st century, hundreds of hyperbaric facilities were established worldwide, marking HBOT's evolution into a sophisticated medical therapy.

Physiological mechanisms and cellular effects

At the cellular level, hyperbaric oxygen therapy (HBOT) creates significant physiological changes through increased oxygen partial pressure. When breathing 100% oxygen at pressures above 1 atmosphere absolute (ATA), the amount of dissolved oxygen in the blood dramatically increases according to Henry's Law. This hyperoxic state leads to oxygen partial pressures up to 10 times normal levels in tissues.

A fascinating aspect of HBOT is the hyperoxic-hypoxic paradox. Despite creating a hyperoxic environment, HBOT triggers cellular responses similar to those seen in hypoxia. This paradox operates through hormesis - where controlled oxidative stress induces beneficial adaptive responses. The increased pressure and oxygen drive the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which act as crucial signaling molecules.

These reactive species activate multiple cellular pathways through redox signaling. Studies have shown HBOT upregulates hypoxia-inducible factor (HIF), extracellular regulated kinases (ERK1/ERK2), and other key mediators. This triggers the synthesis of growth factors and promotes several therapeutic effects:

• Enhanced angiogenesis through increased vascular endothelial growth factor (VEGF) production
• Improved wound healing via fibroblast proliferation and collagen synthesis
• Reduced inflammation by modulating cytokine production
• Activation of antioxidant defenses

HBOT exerts profound effects on immune system function. Research demonstrates it alters the CD4+:CD8+ T cell ratio, reduces lymphocyte proliferation, and enhances neutrophil activity. These immunomodulatory properties help explain its efficacy in conditions like autoimmune diseases and chronic wounds.

At the tissue level, HBOT's ability to increase oxygen diffusion gradients between circulation and surrounding tissues is crucial for wound healing. Studies show it enhances neutrophil function and promotes migration of fibroblasts and macrophages into damaged hypoxic tissue. This facilitates collagen formation, angiogenesis, and bacterial killing.

The cellular response to HBOT involves complex interactions between oxidative stress signaling, inflammatory mediators, and tissue repair mechanisms. Understanding these physiological pathways has been essential for developing therapeutic protocols and identifying new potential applications for hyperbaric medicine.