The Normobaric Oxygen Paradox—Hyperoxic Hypoxic Paradox: A Novel Expedient Strategy in Hematopoiesis Clinical Issues

Abstract

Hypoxia, even at non-lethal levels, is one of the most stressful events for all aerobic organisms as it significantly affects a wide spectrum of physiological functions and energy production. Aerobic organisms activate countless molecular responses directed to respond at cellular, tissue, organ, and whole-body levels to cope with oxygen shortage allowing survival, including enhanced neo-angiogenesis and systemic oxygen delivery. The benefits of hypoxia may be evoked without its detrimental consequences by exploiting the so-called normobaric oxygen paradox. The intermittent shift between hyperoxic-normoxic exposure, in addition to being safe and feasible, has been shown to enhance erythropoietin production and raise hemoglobin levels with numerous different potential applications in many fields of therapy as a new strategy for surgical preconditioning aimed at frail patients and prevention of postoperative anemia. This narrative review summarizes the physiological processes behind the proposed normobaric oxygen paradox, focusing on the latest scientific evidence and the potential applications for this strategy. Future possibilities for hyperoxic-normoxic exposure therapy include implementation as a synergistic strategy to improve a patient’s pre-surgical condition, a stimulating treatment in critically ill patients, preconditioning of athletes during physical preparation, and, in combination with surgery and conventional chemotherapy, to improve patients’ outcomes and quality of life.

Continuous Physiological Monitoring of the Combined Exposure to Hypoxia and High Cognitive Load in Military Personnel

“…However, former studies concluded that this response followed the vasoconstriction and increased blood pressure induced by hyperoxia. These counterintuitive findings support the "hyperoxia-hypoxia" paradox, where increased O 2 from a hyperoxic exposure may induce a hypoxic response that manifests through different mechanisms [50][51][52]. Interestingly though, while the physiological effects of hyperoxia appear negative, several studies previously reported enhanced cognitive outcomes following acute hyperoxic exposures of 30% to 100% O 2 .…”

Oxy-Inflammation in Humans during Underwater Activities

“…Inflammation may be influenced by fiO 2 level, as reported by some authors investigating subjects exposed to hypoxia that showed pulmonary edema caused by inflammatory markers release, including interleukin-6 (IL-6) and protein C-reactive (CRP) [ 24 , 25 , 26 ]. To adapt body tissues to hypoxia, hypoxia-inducible factors (HIFs), a family of heterodimers that constitute a transcription complex that is stabilized by hypoxia [ 26 ] or a return from hyperoxia [ 27 , 28 , 29 , 30 ], are activated to coordinate several transcriptional pathways to optimize metabolic and vascular functions toward low fiO 2 [ 31 ]. Furthermore, HIFs are controlled by prolyl hydroxylase domain (PHD) proteins, a class of “O 2 sensors” that are involved in HIF level regulation and O 2 homeostasis [ 32 ].…”

Hyperbaric oxygen therapy: future prospects in regenerative therapy and anti-aging

“…Hyperoxic-hypoxic paradox has been reported in previous therapeutic uses of oxygen and the effect has been extensively discussed in literature ( Balestra and Kot, 2021 ; Balestra et al, 2023 ). Hyperoxic-normoxic exposure has been shown to exhibit hematopoietic functions and results in the production of erythropoietin and increased levels of haemoglobin ( Salvagno et al, 2022 ). Intermittent conditions of oxidative stress can arise during situations like physical exercise which can generate the similar effect in the form of eliciting antioxidant protection and erythropoietin production ( Revelli et al, 2013 ; Fratantonio et al, 2021 ).…”