Neocytolysis on Descent from Altitude: A Newly Recognized Mechanism for the Control of Red Cell Mass

Rice, Lawrence; Ruiz, Wilson; Driscoll, T. B.; Whitley, Carl E.; Tapia, R; Hachey, David L.; Gonzáles, Gustavo F.; Alfrey, Clarence P.

doi:10.7326/0003-4819-134-8-200104170-00010

Cited by 127 publications

(134 citation statements)

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“…Thus, when altitude natives, or even altitude sojourners, return to sea level, there is a suppression of erythropoietin (Faura et al, 1969;Jelkman, 1992;Richalet et al, 1993;Gunga et al, 1996;Levine and Stray-Gundersen, 1997;Chapman et al, 1998), a dramatic reduction in iron turnover and bone marrow production of erythroid cell lines (Huff et al, 1951;Reynafarje et al, 1959), and a marked decrease in red cell survival time (Reynafarje et al, 1959). This increase in red cell destruction with suppression of EPO levels has been termed neocytolysis and has been observed under other conditions of a relative increase in oxygen content (Alfrey et al, 1996a(Alfrey et al, , 1996b(Alfrey et al, , 1997Rice and Alfrey, 2000;Rice et al, 2001). Both the rapid ubiquitination and destruction of HIF-1a and neocytolysis (which may be its clinical manifestation) may compromise the ability of short-duration, intermittent hypoxic exposures to induce a sustained increase in the red cell mass.…”

Section: Erythropoietic Effect Of High Altitudementioning

confidence: 97%

Intermittent Hypoxic Training: Fact and Fancy

Levine

2002

High Altitude Medicine & Biology

160

142

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LTITUD E TRAINING has been used frequently by endurance athletes to enhance performance. However, not all athletes or teams have the resources to travel to high altitude environments on a regular basis. Moreover, issues such as availability of adequate training facilities have limited the use of mountain-based altitude training. In the last few years, there has been a remarkable increase in the number of techniques designed to "bring the mountain to the athlete." Nitrogen houses, hypoxia tents, and special breathing apparatuses to provide inspired hypoxia at rest and during exercise, all have been developed and promoted to simulate what are perceived as the critical elements of altitude training.Intermittent hypoxic training (IHT) refers to the discontinuous use of normobaric or hypobaric hypoxia, in an attempt to reproduce some of these key features of altitude acclimatization, with the ultimate goal to improve sea-level athletic performance. In general, IHT can be divided into two different strategies: (1) providing hypoxia at rest with High Alt Med Biol. 3:177-193, 2002.-Intermittent hypoxic training (IHT) refers to the discontinuous use of normobaric or hypobaric hypoxia, in an attempt to reproduce some of the key features of altitude acclimatization, with the ultimate goal to improve sea-level athletic performance. In general, IHT can be divided into two different strategies: (1) providing hypoxia at rest with the primary goal being to stimulate altitude acclimatization or (2) providing hypoxia during exercise, with the primary goal being to enhance the training stimulus. Each approach has many different possible application strategies, with the essential variable among them being the "dose" of hypoxia necessary to achieve the desired effect. One approach, called living high-training low, has been shown to improve sea-level endurance performance. This strategy combines altitude acclimatization (2500 m) with low altitude training to ensure high-quality training. The opposite strategy, living low-training high, has also been proposed by some investigators. The primacy of the altitude acclimatization effect in IHT is demonstrated by the following facts: (1) living high-training low clearly improves performance in athletes of all abilities, (2) the mechanism of this improvement is primarily an increase in erythropoietin, leading to increased red cell mass, V O 2max , and running performance, and (3) rather than intensifying the training stimulus, training at altitude or under hypoxia leads to the opposite effect-reduced speeds, reduced power output, reduced oxygen flux-and therefore is not likely to provide any advantage for a well-trained athlete.

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Section: Erythropoietic Effect Of High Altitudementioning

confidence: 97%

Intermittent Hypoxic Training: Fact and Fancy

Levine

2002

High Altitude Medicine & Biology

160

142

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“…The theory of neocytolysis has been confirmed in high-altitude residents with erythrocytosis descending from altitude to sea level [32]. In these individuals, production of red cells remains normal as reflected by a normal reticulocyte count, while the red cell mass decreases by 10%.…”

Section: Neocytolysismentioning

confidence: 99%

Implications of Neocytolysis for Optimal Management of Anaemia in Chronic Kidney Disease

Alfrey

Fishbane²

2007

Nephron Clin Pract

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Erythropoietin is the major hormone regulator of erythrocyte production promoting the survival, as well as the differentiation and maturation, of erythroid progenitor cells. In addition to these well-characterized effects, it appears that an erythropoietin-responsive non-erythroid mechanism also mediates the selective destruction of young circulating erythrocytes (neocytes) when red cell mass becomes excessive – a process termed ‘neocytolysis’. Endothelial cells appear to respond to a rapid decrease in circulating levels of erythropoietin by secreting cytokines (including TGF-α), which signal reticuloendothelial phagocytes to destroy neocytes. The result is a more rapid decrease in red cell mass than can be explained by natural erythrocyte senescence alone. The current pharmacologic approach to treatment of anaemia in chronic kidney disease may cause neocytolysis and could keep therapy from reaching its full potential. Understanding neocytolysis and its relationship to fluctuating serum erythropoietin levels might help to better understand optimal treatment with erythropoietic agents.

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“…Changes in lifespan have been observed either as the result of pathological condition, like in beta thalassemia or sickle cell disease [2,3] or as a physiological adaptive response to particular environments, requiring a fast decrease in circulating red cells mass [4,5,6]. While the pathological variation of RBC lifespan has received much interest because of obvious medical implications, less is known about the cellular and molecular mechanisms underlying erythrocyte demise over physiological adaptive responses, although investigations have been made on different human experimental models.…”

Section: Introductionmentioning

confidence: 99%

“…While the pathological variation of RBC lifespan has received much interest because of obvious medical implications, less is known about the cellular and molecular mechanisms underlying erythrocyte demise over physiological adaptive responses, although investigations have been made on different human experimental models. In high altitude polycythemic dwellers returning to a normoxic environment, a fast decrease in RBC mass is obtained by a decrease in EPO synthesis and by destruction of red cells [5,6]. A similar process occurs also in astronauts to alleviate the “pseudopolycythemia” that ensues over the first days in low gravity, due to a fast redistribution of blood from lower body to thorax and reduction of plasma volume [7,8].…”

Section: Introductionmentioning

confidence: 99%

Survival and Senescence of Human Young Red Cellsin Vitro

Risso

Ciana

Achilli

et al. 2014

Cell Physiol Biochem

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Background: A number of experimental investigations in vivo suggest that in humans a decrease of circulating erythrocyte number ensues whenever erythropoietin (EPO) plasma level decreases. Since the process seems to selectively eliminate young red cells (neocytes), it has been named neocytolysis. The experimental models in vivo have revealed and documented multiple forms of neocytolysis but have not fully elucidated the specificity of the target red cells and the relation with EPO level changes. In an attempt to better characterize the neocytolytic process, we have undertaken an in vitro investigation on age-ranked human red cells. Methods: By centrifugation on Percoll density gradient we separated the red cells population into three subsets, neocytes, middle-aged and old. Then we comparatively investigated the kinetics of survival of the subsets cultured under different conditions: with medium alone, with 10% autologous plasma, with EPO, alone or in combination with autologous monocytes. Results: Neocytes showed a viability and a survival rate lower than the other red cells when cultured in medium or with 10% plasma. EPO at physiological doses increased their survival rate, but not that of the other subsets. This effect was enhanced by co-culture with monocytes. Conclusion: Likely neocytes are more sensitive than the other RBCs subsets to presence or absence of survival signals, such as EPO or plasma or monocytes derived factors. These observations could provide an insight into the link between the decrease in EPO plasma level and the reduction of circulating red cells mass and account for the specificity of neocytes clearance.

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Neocytolysis on Descent from Altitude: A Newly Recognized Mechanism for the Control of Red Cell Mass

Abstract: Neocytolysis and the role of erythropoietin are confirmed in persons with polycythemia who descend from high altitude. This may have implications that extend beyond space and altitude medicine to renal disease and other situations of erythropoietin suppression, hemolysis, and polycythemia.

Cited by 127 publications

References 12 publications

Intermittent Hypoxic Training: Fact and Fancy

Intermittent Hypoxic Training: Fact and Fancy

Implications of Neocytolysis for Optimal Management of Anaemia in Chronic Kidney Disease

Survival and Senescence of Human Young Red Cellsin Vitro

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