Physiological and Clinical Impact of Repeated Inhaled Oxygen Variation on Erythropoietin Levels in Patients After Surgery

Abstract

The “Normobaric Oxygen Paradox” (NOP) is a physiologic mechanism that induces an increase of endogenous erythropoietin (EPO) production by creating a state of relative hypoxia in subjects previously exposed to hyperoxia, followed by a rapid return to normoxia. Oxygen exposure duration and inspired oxygen fraction required to observe a significant increase in EPO or hemoglobin are not clearly defined. Consequently, we here study the effect of one model of relative hypoxia on EPO, reticulocytes and hemoglobin stimulation in patients after surgery. Patients were prospectively randomized in two groups. The O2 group (n = 10) received 100% oxygen for 1 h per day for eight consecutive days, via a non-rebreathing mask. The control group (n = 12) received no oxygen variation. Serum EPO, hemoglobin and reticulocyte count were measured on admission and postoperatively on days seven and nine. Percentage EPO at day nine with respect to the baseline value was significantly elevated within the groups [O2 group: 323.7 (SD ± 139.0); control group: 365.6 (SD± 162.0)] but not between them. No significant difference was found between the groups in terms of reticulocytes count and hemoglobin. Our NOP model showed no difference on EPO increase between the two groups. However, both groups expressed separately significant EPO elevation.

Oxygen: A Stimulus, Not “Only” a Drug

“…Surprisingly, new data show that even a minimal increase in the partial pressure of oxygen efficiently triggers cellular reactions [9,10]. As we already expressed in previous works, "some decades ago, on the physiological side, the two parameters that characterize extreme environments were identified as eliciting the production of two particular elements: hypoxia-inducible factors and heat-shock proteins.…”

“…We may need to consider oxygen variations in the mitochondrion as the most potent homeorhetic trigger in nature. Considering this no wonder that even variations of 10% of the inspired oxygen fraction may be effective in humans and cultured cells [9,10,18]. It is now known that genes are not always activated.…”

“…Interestingly, several articles have been interested in increasing hemoglobin and oxygen exposure [9,14,[22][23][24]. To achieve such an increase in a fast way, small deltas were elicited; for a more extended response, higher oxygen variations and more distant (less frequent) variations were needed [21].…”

Oxidative Stress Response’s Kinetics after 60 Minutes at Different (30% or 100%) Normobaric Hyperoxia Exposures

“…Based on the current literature, several factors such as FiO 2 [11,15,24,25], duration and frequency [26][27][28], or pressure of exposure-either normobaric, hypobaric, or hyperbaric [15,26,29]-may influence the ability to reach a specific clinical or molecular effect.…”

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

“…It appears that fluctuations in oxygen concentration are translated by cells as a lack of oxygen and can trigger the hypoxic stress response even when there is no persistent hypoxia. This phenomenon happens especially with small and cyclical variations in partial oxygen pressure [16][17][18] and is linked with increased production of erythropoietin (EPO) in humans [15,19]. This review will discuss the main studies related to this "normobaric oxygen paradox" and its mechanism with a specific concern for clinical issues in hematopoietic physiology.…”