Depressant Effects of High Concentrations of Inspired Oxygen on Erythrocytogenesis. Observations on Patients With Sickle Cell Anemia With a Description of the Observed Toxic Manifestations of Oxygen 12

Reinhard, Edward H.; Moore, Carl V.; Dubach, Reubenia; Wade, Leo

doi:10.1172/jci101539

Cited by 61 publications

(16 citation statements)

References 18 publications

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“…Despite reticulocytosis comparable to that observed in our patients with sickle cell anemia, the red cells of these patients did not show accelerated K fluxes when incubated in N~ rather than O2 (Table V). We also studied the effect of N2 on K transport in S-S blood in which reticulocytosis was inhibited by keeping patients in a tent breathing 50 per cent O~ for 1 to 2 weeks prior to the experiment (17). The results, also sum-marized in Table V, show that exposure of S-S ceils to N2 with production of sickling caused net K loss with accelerated K fluxes in the presence of many or a few reticulocytes.…”

Section: (B) the Gffed Of Prevention Of Sickling On K Transport In Anmentioning

confidence: 97%

The Effects of Sickling on Ion Transport

Tosteson

Carlsen

Dunham

1955

The Journal of General Physiology

137

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The conversion of red cells of patients with sickle cell anemia (S-S) from biconcave disk to sickle shape by removal of oxygen was found to increase the fraction of medium trapped in cells packed by centrifugation from 0.036 (S.E. 0.003) to 0.106 (S.E. 0.004). The fraction of water in the cells (corrected for trapped medium) was not affected by this shape transformation. Cation transport, however, was changed profoundly. S-S cells incubated in N2 rather than O2 showed net K loss with acceleration of both influx and outflux. That this change in K transport was due to the process of sickling was indicated by (1) the persistence of the effect in the absence of plasma, (2) the absence of the effect in hypoxic S-S cells in which sickling was inhibited by alkali or carbon monoxide, (3) the reversal of the effect when sickling was reversed by exposure to O2, and (4) the independence of the effect from such potentially important factors as age of the cell population. The acceleration of K transport by sickling is probably mediated by modification of the cell surface rather than the cell interior since concentrated sickle hemoglobin solutions in O2 or N2 did not show selective affinity for K. In molecular terms, the effect of sickling on K transport can be explained by presuming that the shape change (1) opens pathways for the free diffusion of K, and (2) accelerates K transport by a non-diffusion carrier process. The evidence for the former mechanism included (a) dependence of K influx into sickled cells on the concentration of K in the medium, and (b) increase in the total cation content of sickled cells with increasing pH. Observations suggestive of a carrier process included (a) the failure of sickled cell K concentration to become equal to external K concentration even after 48 hours, (b) the deviation of the flux ratio from that characteristic of diffusion, and (c) the dependence of K influx on glycolysis.

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Section: (B) the Gffed Of Prevention Of Sickling On K Transport In Anmentioning

confidence: 97%

The Effects of Sickling on Ion Transport

Tosteson

Carlsen

Dunham

1955

The Journal of General Physiology

137

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“…mm. The differential count of 100 leucocytes showed 1 eosinophile, 1 myelocyte, 6 band forms, 63 segmented neutrophiles, 19 lymphocytes, and 10 monocytes. Marked sickling of the red cells was present in the supravital preparation.…”

Section: Subjects With Normal Blood Formationmentioning

confidence: 98%

“…Reinhard et al (6) emphasized that patients with chronic hemolytic anemias offer the following advantages as subjects for a study of the effects of an agent which depresses the rate of erythrocytogenesis: 1) the life span of the average red cell in the circulation is much shorter than normal; therefore, any decrease in the rate of delivery of new cells is followed more quickly by a fall in the red cell count, hemoglobin and hematocrit; 2) reticulocytes are greatly increased in number so that a wider range is available through which a decrease may be demonstrated; 3) if the rate of red cell destruction is assessed continuously by determination of the daily total urobilinogen excretion and is found to be reasonably stable, consistent and progressive changes in daily red cell counts reflect changes in the rate of formation and delivery of the red cells to the circulation. The only pa- 4 These masks are designed to prevent rebreathing from the reservoir bag.…”

Section: Hemolytic Anemiasmentioning

confidence: 99%

“…tients with chronic hemolytic anemias who both satisfied these conditions and were available as subjects for these studies were those with sickle cell anemia and congenital hemolytic anemia. Sickle cell anemia was included because it was considered desirable to confirm the previous observations (6) as a part of this more comprehensive study.…”

Section: Hemolytic Anemiasmentioning

confidence: 99%

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The Role of Oxygen in the Regulation of Erythropoiesis. Depression of the Rate of Delivery of New Red Cells to the Blood by High Concentrations of Inspired Oxygen 12

Tinsley¹,

Moore²,

Dubach³

et al. 1949

J. Clin. Invest.

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Oxygen tension of the environment is regarded as one of the principal regulators of the rate of erythropoiesis. This concept is based largely on the fact that stimulation of red blood cell formation regularly occurs at high altitudes, or under conditions of decreased oxygen tension. Evidence that the converse is true, that high tensions of oxygen can decrease erythrocyte formation, is more fragmentary. A few experiments have demonstrated that animals become anemic within a few weeks when placed in atmospheres containing 60 per cent or more of oxygen at normal barometric pressure (1-3). Early attempts to demonstrate a similar depressant effect in human subjects were unsuccessful, usually because the concentrations of oxygen were not sufficiently high, or because the observations were continued for only short periods of time (4, 5). Since the human red cell normally survives in the circulation for approximately 120 days, it is evident that special technics must be used, or the exposure to high concentrations of oxygen must be continued for weeks if an unequivocal drop in the red blood cell level of a normal subject is to be produced.Reinhard and his associates (6) circumvented these difficulties by using patients with sickle cell anemia as subjects for their studies. Because the survival time of the erythrocyte in sickle cell anemia is short (7,8), and the reticulocyte level is high, it was possible to show that the continuous administration of 80 per cent oxygen by face

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“…* This prediction was confirmed by Bert himself and others working at high altitudes. 2 : 3 On the other hand Reinhart et al 4 and later Smith 5 have observed that high concentration of oxygen had a depressant effect on erythropoiesis. These observations and others eventually paved the way for the hypothesis that red cell production is influenced by the tissue oxygen tension.…”

mentioning

confidence: 97%