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Increased Serum Erythropoietin despite Normalized Hb Concentration and Arterial O 2 Saturation in Chronic Mountain Sickness after Isovolemic Hemodilution
Author(s) -
Villafuerte Francisco C,
Anza Cecilia,
Heinrich Erica C,
Tift Michael,
Figueroa Romulo,
Vizcardo Gustavo,
Macarlupu Jose L,
Wagner Peter D,
Simonson Tatum S
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb592
Subject(s) - medicine , erythropoietin , anesthesia , hypoxemia , transferrin saturation , blood volume , hematocrit , cardiology , ferritin , serum ferritin
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 O 2 saturation (SaO 2 ) and/or whether the normalization of Hb affects the erythropoietic stimulus. Thus, we sought to investigate the effect of isovolemic hemodilution on resting arterial PO 2 (PaO 2 ), SaO 2 , arterial O 2 content (CaO 2 ), 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 O 2 saturation (SpO 2 ; 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 PaO 2 , SaO 2 , serum EPO, iron, ferritin, and transferrin saturation were similar in both non‐CMS and CMS groups, while CaO 2 was higher in CMS (24.4 ± 1.9 vs 20.7 ± 1.6 mlO 2 /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. PaO 2 and SaO 2 remained essentially unchanged, whereas CaO 2 decreased (from 24.4 ± 1.9 to 20 ± 0.8 mlO 2 /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 SaO 2 . Despite this, serum EPO increased dramatically reflecting erythropoietic stimulus. It is possible that chronic EE determines a higher set‐point for Hb and CaO 2 in CMS subjects, and thus even reduction to non‐CMS values is sensed as relative tissue hypoxia due to reduced O 2 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 .