Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the “normobaric oxygen paradox”

Abstract

Renal (peritubular) tissue hypoxia is a well-known physiological trigger for erythropoietin (EPO) production. We investigated the effect of rebound relative hypoxia after hyperoxia obtained under normo- and hyperbaric oxygen breathing conditions. A group of 16 healthy volunteers were investigated before and after a period of breathing 100% normobaric oxygen for 2 h and a period of breathing 100% oxygen at 2.5 ATA for 90 min (hyperbaric oxygen). Serum EPO concentration was measured using a radioimmunoassay at various time points during 24-36 h. A 60% increase (P < 0.001) in serum EPO was observed 36 h after normobaric oxygen. In contrast, a 53% decrease in serum EPO was observed at 24 h after hyperbaric oxygen. Those changes were not related to the circadian rhythm of serum EPO of the subjects. These results indicate that a sudden and sustained decrease in tissue oxygen tension, even above hypoxia thresholds (e.g., after a period of normobaric oxygen breathing), may act as a trigger for EPO serum level. This EPO trigger, the "normobaric oxygen paradox," does not appear to be present after hyperbaric oxygen breathing.

Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation

“…11 In addition, HBO treatment has been shown to reduce systemic EPO levels in healthy volunteers. 10 Because our current in vitro studies indicated that EPO-EPOR signaling inhibits SDF-1-induced migration of UCB CD34…”

“…Therefore, we investigated whether EPO signaling negatively affects the efficiency of UCB CD34 1 HSPC transplantation, and if inhibition of EPO signaling would improve BM homing of transplanted HSPCs. Because hyperbaric oxygen (HBO) therapy has been shown to lower EPO levels in healthy volunteers, 10 and as in our previous experience, HBO treatment of the host before UCB CD34 1 cell infusion was associated with improved engraftment of UCB CD34 1 cells in a murine model, 11 we examined HBO effects on HSPC differentiation and homing in vivo. In the first in-human clinical trial, HBO treatment of UCB transplantation recipients was well tolerated, significantly reduced serum EPO levels, and resulted in encouraging rates and kinetics of UCB blood count recovery.…”

Increasing EPO using the normobaric oxygen paradox: a ‘not so simple’ task

“…

Since the first report presenting the possibility to increase erythropoietin (EPO) with a single nonhypoxic stimulus (Balestra et al 2006), its clinical utility has been postulated in neuroprotection and cardioprotection as a pre-operative treatment, as well as in the treatment of sepsis patients (Calzia et al 2010).The repetition of this simple stimulus has been used to increase haemoglobin and reticulocytes in anaemic patients (Burk 2007. The possible 'doping-like' effect of such a method has also been recently discussed (Balestra & Germonpre 2010).

Although the normobaric oxygen paradox (NOP) mechanism seems to be proved, our experience demonstrates that to effectively show a significant increase in EPO after one single exposure to normobaric oxygen is not so easy.

…”

“…To show an increase at a specific moment of the day we found that a simple correction for baseline levels matching was not sufficient and an individual matching of the circadian rhythm was needed (Balestra et al 2006). The modest acute increase in EPO was shown to be effective to increase haemoglobin when repeated for several days (Burk 2007).…”

350 años de la medicina hiperbárica: aspectos históricos, fisiopatogénicos y terapéuticos

“…El oxígeno captado con la respiración también varía durante el tratamiento en la cámara hiperbárica, debido a que, durante el descenso a la profundidad, la presión intraalveolar de oxígeno aumenta; esto sucede como una respuesta fisiológica que responde a la ley de Boyle y a la ley de Dalton. La ley de Boyle enuncia que, a una temperatura constante, la presión de un gas es inversamente proporcional a su volumen, mientras la ley de Dalton enuncia que en una mezcla de gases cada elemento ejerce una presión proporcional a su fracción del volumen total; dichas leyes explican el efecto de la presión parcial de oxí-geno y su disposición intraalveolar [11][12][13][14] . En las infecciones, los radicales libres funcionan oxidando a las proteínas y los lípidos de membrana, dañando el ADN y las funciones metabólicas bacterianas.…”