Marie Klein1,2, Lars Kaestner3,4, Anna Y Bogdanova5, Giampaolo Minetti6, Silvia Rudloff7, Carsten Lundby8,9, Asya Makhro5, Elena Seiler5, Ankie van Cromvoirt5, Simone Fenk5, Greta Simionato3,4,10, Laura Hertz3, Steffen Recktenwald3, Larissa Schäfer11, Thomas Haider12, Sebastian Fried13, Christian Borsch7, Hugo H Marti14, Anja Sander15, Heimo Mairbäurl1,2,16. 1. Medical Clinic VII, Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany. 2. Translational Pneumology, University Hospital Heidelberg, Heidelberg, Germany. 3. Experimental Physics, Dynamics of Fluids Group, Saarland University, Saarbrücken, Germany. 4. Theoretical Medicine and Biosciences, Campus University Hospital, Saarland University, Homburg, Germany. 5. Red Blood Cell Research Group, Institute of Veterinary Physiology, University of Zürich, Zürich, Switzerland. 6. Department of Biology and Biotechnology "L Spallanzani", Laboratories of Biochemistry, University of Pavia, Pavia, Italy. 7. Analytical Platform, Stable Isotopes, and Cell Biology, Institute of Nutritional Sciences, Justus Liebig University Giessen, Giessen, Germany. 8. The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Hillerød, Denmark. 9. Inland Norway University of Applied Sciences, Lillehammer, Norway. 10. Institute for Clinical and Experimental Surgery, Saarland University, Campus University Hospital, Homburg, Germany. 11. Department of Anaesthesiology and Intensive Care Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria. 12. Department of Cardiology, University Hospital Zürich, Zürich, Switzerland. 13. Department of Anaesthesiology, University Hospital Heidelberg, Heidelberg, Germany. 14. Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany. 15. Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Heidelberg, Germany. 16. Translational Lung Research Centre Heidelberg (TLRC), Part of the German Centre for Lung Research (DZL), Heidelberg, Germany.
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.
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.
Authors: Felix Maurer; Thomas John; Asya Makhro; Anna Bogdanova; Giampaolo Minetti; Christian Wagner; Lars Kaestner Journal: Cells Date: 2022-04-11 Impact factor: 7.666
Authors: Greta Simionato; Antonia Rabe; Joan Sebastián Gallego-Murillo; Carmen van der Zwaan; Arie Johan Hoogendijk; Maartje van den Biggelaar; Giampaolo Minetti; Anna Bogdanova; Heimo Mairbäurl; Christian Wagner; Lars Kaestner; Emile van den Akker Journal: Cells Date: 2022-03-23 Impact factor: 6.600
Authors: Antonia Rabe; Alexander Kihm; Alexis Darras; Kevin Peikert; Greta Simionato; Anil Kumar Dasanna; Hannes Glaß; Jürgen Geisel; Stephan Quint; Adrian Danek; Christian Wagner; Dmitry A Fedosov; Andreas Hermann; Lars Kaestner Journal: Biomolecules Date: 2021-05-12