Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women

Abstract

New Findings r What is the central question of this study?Does a clinically relevant intravenous dose of erythropoeitin affect the hypoxic ventilatory response and/or hypoxic pulmonary vasoconstriction in healthy humans? r What is the main finding and its importance?Erythropoeitin does not influence the ventilatory and pulmonary vascular responses to acute hypoxia in men or women.Sustained and chronic hypoxia lead to an increase in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical i.v. dose of recombinant human erythropoietin (50 IU kg −1 ) on the isocapnic HVR and HPV in seven male and seven female subjects by exposing them to hypoxia for 20 min (end-tidal P O 2 ß50 mmHg) while measuring their ventilation and estimating pulmonary arterial pressure from the maximal velocity of the regurgitant jet over the tricuspid valve during systole ( P max ) with echocardiography. In the placebo session, after 5 and 20 min men responded with an increase in ventilation by 0.0056 and 0.0023 l min −1 kg −1 %S pO 2 −1 , respectively, indicating the presence of hypoxic ventilatory depression. In women, the increase in ventilation was 0.0067 and 0.0047 l min −1 kg −1 %S pO 2 −1 , respectively. In both sexes, erythropoietin did not alter these responses significantly. In the placebo session, mean P max increased by 6.1 ± 0.7 mmHg in men (P = 0.035) and by 8.4 ± 1.4 mmHg in women (P = 0.020) during the hypoxic exposure, whereby women had a ß5 mmHg lower end-tidal P CO 2 . Erythropoietin did not alter these responses; in men, P max increased by 7.5 ± 1.1 mmHg (n.s. versus placebo) and in women by 9.7 ± 2.2 mmHg (n.s. versus placebo). We conclude that women tended to have a greater HPV in placebo conditions and that a clinical dose of erythropoietin has no effect on the HVR and HPV in either sex.

Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5300 m)

“…The association of EPO with HPV changes might not imply causality, because EPO also increases with increasing altitude exposure as the kidneys themselves experience a reduction in their local P O 2 . Furthermore, there are no data to indicate that EPO causes pulmonary vasoconstriction (Kuriyama et al 2014;Berendsen et al 2016). Our failure to find any associations of the other chosen biomarkers with PA pressure changes might relate to the fact that other possibly relevant vasoactive mediators also known to alter HPV, such as several products of prostaglandin metabolism and microRNAs, might be more relevant.…”

“…Furthermore, there are no data to indicate that EPO causes pulmonary vasoconstriction (Kuriyama et al 2014;Berendsen et al 2016). Furthermore, there are no data to indicate that EPO causes pulmonary vasoconstriction (Kuriyama et al 2014;Berendsen et al 2016).…”