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

Greta Simionato, Heimo Mairbäurl, Anja Sander, Hugo H Marti, Christian Borsch, Sebastian Fried, Thomas Haider, Larissa Schäfer, Steffen Recktenwald, Laura Hertz, Marie Klein, Simone Fenk, Ankie van Cromvoirt, Elena Seiler, Asya Makhro, Carsten Lundby, Silvia Rudloff, Giampaolo Minetti, Anna Y Bogdanova, Lars Kaestner

Journal: Acta physiologica (Oxford, England) 2021;232(3):e13647

PMID: 33729672

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 C2- and 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 C- (normoxia) and 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.

© 2021 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.

Address: Medical Clinic VII, Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Translational Pneumology, University Hospital Heidelberg, Heidelberg, Germany.; Experimental Physics, Dynamics of Fluids Group, Saarland University, Saarbrücken, Germany.; Theoretical Medicine and Biosciences, Campus University Hospital, Saarland University, Homburg, Germany.; Red Blood Cell Research Group, Institute of Veterinary Physiology, University of Zürich, Zürich, Switzerland.; Department of Biology and Biotechnology "L Spallanzani", Laboratories of Biochemistry, University of Pavia, Pavia, Italy.; Analytical Platform, Stable Isotopes, and Cell Biology, Institute of Nutritional Sciences, Justus Liebig University Giessen, Giessen, Germany.; The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Hillerød, Denmark.; Inland Norway University of Applied Sciences, Lillehammer, Norway.; Institute for Clinical and Experimental Surgery, Saarland University, Campus University Hospital, Homburg, Germany.; Department of Anaesthesiology and Intensive Care Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.; Department of Cardiology, University Hospital Zürich, Zürich, Switzerland.; Department of Anaesthesiology, University Hospital Heidelberg, Heidelberg, Germany.; Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.; Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Heidelberg, Germany.; Translational Lung Research Centre Heidelberg (TLRC), Part of the German Centre for Lung Research (DZL), Heidelberg, Germany.

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