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. 2021 Jul;232(3):e13647.
doi: 10.1111/apha.13647. Epub 2021 Mar 17.

Absence of neocytolysis in humans returning from a 3-week high-altitude sojourn

Marie Klein  1   2 , Lars Kaestner  3   4 , Anna Y Bogdanova  5 , Giampaolo Minetti  6 , Silvia Rudloff  7 , Carsten Lundby  8   9 , Asya Makhro  5 , Elena Seiler  5 , Ankie van Cromvoirt  5 , Simone Fenk  5 , Greta Simionato  3   4   10 , Laura Hertz  3 , Steffen Recktenwald  3 , Larissa Schäfer  11 , Thomas Haider  12 , Sebastian Fried  13 , Christian Borsch  7 , Hugo H Marti  14 , Anja Sander  15 , Heimo Mairbäurl  1   2   16
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Absence of neocytolysis in humans returning from a 3-week high-altitude sojourn

Marie Klein et al. Acta Physiol (Oxf). 2021 Jul.

Abstract

Aims: Total haemoglobin mass (tot-Hb) increases during high-altitude acclimatization. Normalization of tot-Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m).

Methods: Newly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19-day high-altitude sojourn by ingestion of 13 C2- and 15 N-labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot-Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling.

Results: Tot-Hb increased by 4.7% ± 2.7% at high altitude and returned to pre-altitude values within 11 days after descent. Elimination of 13 C- (normoxia) and 15 N- (high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71-positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3-4 days after descent and normalized slowly. There was no indication of haemolysis.

Conclusion: We confirm a rapid normalization of tot-Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes.

Keywords: erythropoiesis; high altitude; membrane protein 4.1R; neocytolysis; post-altitude; total haemoglobin mass.

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References

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