Increased Serum Erythropoietin despite Normalized Hb Concentration and Arterial O2 Saturation in Chronic Mountain Sickness after Isovolemic Hemodilution
Authors: Villafuerte Francisco C , Anza Cecilia , Heinrich Erica C , Tift Michael , Figueroa Romulo , Vizcardo Gustavo , Macarlupu Jose L , Wagner Peter D , Simonson Tatum S 
Published: June 2021

Excessive erythrocytosis (EE) is a hallmark of Chronic Mountain Sickness (CMS), an incapacitating condition among high‐altitude residents. EE is associated with accentuated hypoxemia and neurological symptoms. Periodic hemodilution is a common treatment used to normalize excessive red blood cell count and relieve symptomatology. However, it is unclear whether relief results from an improvement of arterial O2 saturation (SaO2) and/or whether the normalization of Hb affects the erythropoietic stimulus. Thus, we sought to investigate the effect of isovolemic hemodilution on resting arterial PO2 (PaO2), SaO2, arterial O2 content (CaO2), serum EPO, iron profile, and CMS score in CMS subjects. Six CMS and eight non‐CMS male residents of Cerro de Pasco, Peru (4350m), of similar age participated in the study. The CMS group exhibited significantly higher Hb concentration (22.2 ± 1.2 vs 17.8 ± 1.3 g/dl, p<0.001) and CMS score (10.0 ± 6.6 vs 1.1 ± 1.1, p<0.01) with a lower pulse O2 saturation (SpO2; 84.7 ± 1.0 vs 88.3 ± 1.6%, p<0.05). Radial artery catheters were placed to obtain arterial blood measurements. For isovolemic hemodilution, a venous catheter was placed in the arm of CMS subjects to remove ~2–4 units of blood (1675 ± 442 ml) for a reduction of ~19% pre‐hemodilution Hb value. Isovolemia was maintained with an equivalent volume of plasma substitute (Haemaccel®). Baseline PaO2, SaO2, serum EPO, iron, ferritin, and transferrin saturation were similar in both non‐CMS and CMS groups, while CaO2 was higher in CMS (24.4 ± 1.9 vs 20.7 ± 1.6 mlO2/dl, p<0.001). At 36 hours post‐hemodilution, Hb in the CMS group decreased by 20.1 ± 1.6 % (from 22.2 ± 1.2 to 17.7 ± 0.6 g/dl, p<0.001), matching non‐CMS subject values. PaO2 and SaO2 remained essentially unchanged, whereas CaO2 decreased (from 24.4 ± 1.9 to 20 ± 0.8 mlO2/dl, p<0.001). A substantial drop was observed in serum iron (from 112.3 ± 44 to 60.8 ± 30.3 μg/dl, p<0.002) and transferrin saturation (from 28.0 ± 10.8 to 17.7 ± 8.2%, p<0.013). Serum EPO increased significantly after hemodilution (from 25.6 ± 7.6 to 68.2 ± 25.8 mIU/ml, p<0.006), resulting in higher values compared to pre‐hemodilution and non‐CMS subjects (15.9 ± 8.4 mIU/ml). After Hb normalization, CMS symptomatology improved (from 10.0 ± 6.6 to 1.2 ± 1.1, p<0.01) without a significant increase in SaO2. Despite this, serum EPO increased dramatically reflecting erythropoietic stimulus. It is possible that chronic EE determines a higher set‐point for Hb and CaO2 in CMS subjects, and thus even reduction to non‐CMS values is sensed as relative tissue hypoxia due to reduced O2 delivery. In addition, iron depletion could also contribute to EPO expression through inhibition of prolyl hydroxylase enzymes and HIF stabilization.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.