Medical Clinic VII, Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Translational Pneumology, University Hospital Heidelberg, Heidelberg, Germany.
Acta Physiol (Oxf). 2021 Jul;232(3):e13647. doi: 10.1111/apha.13647. Epub 2021 Mar 17.
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).
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.
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.
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.
血红蛋白总量(tot-Hb)在高原适应过程中增加。人们认为,当海拔下降时,tot-Hb 的正常化是通过新生红细胞的选择性破坏即新生红细胞溶解来实现的。由于缺乏令人信服的新生红细胞溶解的实验证据,我们在因特拉肯峰研究站(JFJRS;3450 米)进行了一项新生成的红细胞在停留后的存活的前瞻性研究。
12 名男性受试者(平均年龄 23.3 岁)在常氧(110 米)和 19 天的高海拔逗留期间分别通过摄入 C2-和 N-标记的甘氨酸进行年龄队列标记。通过同位素比值质谱法测定血红蛋白、总血红蛋白、网织红细胞计数、红细胞膜蛋白 4.1a/4.1b 比值和数学建模来测量在常氧和高海拔环境中生成的红细胞的消除动力学。
在高海拔时 tot-Hb 增加了 4.7%±2.7%,在海拔下降后 11 天内恢复到高原前的值。C-(常氧)和 N-(高海拔)标记的红细胞的消除没有差异。在海拔下降后,促红细胞生成素水平和 CD71 阳性网织红细胞计数迅速下降。在高海拔时 4.1a/4.1b 比值降低,并在海拔下降后持续低 3-4 天,然后缓慢恢复正常。没有溶血的迹象。
我们证实了在海拔下降时 tot-Hb 的快速正常化。基于在高海拔时标记的红细胞年龄队列没有加速清除、网织红细胞计数和 4.1a/4.1b 比值的变化模式以及建模的结果,这种下降不是通过新生红细胞溶解,而是通过降低的红细胞生成率和正常清除衰老的红细胞来实现的。