We hypothesize that plasma volume decrease (DeltaPV) induced by high-altitude (HA) exposure and intense exercise is involved in the limitation of maximal O(2) uptake (VO(2)(max)) at HA. Eight male subjects were decompressed for 31 days in a hypobaric chamber to the barometric equivalent of Mt. Everest (8,848 m). Maximal exercise was performed with and without plasma volume expansion (PVX, 219-292 ml) during exercise, at sea level (SL), at HA (370 mmHg, equivalent to 6, 000 m after 10-12 days) and after return to SL (RSL, 1-3 days). Plasma volume (PV) was determined at rest at SL, HA, and RSL by Evans blue dilution. PV was decreased by 26% (P < 0.01) at HA and was 10% higher at RSL than at SL. Exercise-induced DeltaPV was reduced both by PVX and HA (P < 0.05). Compared with SL, VO(2)(max) was decreased by 58 and 11% at HA and RSL, respectively. VO(2)(max) was enhanced by PVX at HA (+9%, P < 0.05) but not at SL or RSL. The more PV was decreased at HA, the more VO(2)(max) was improved by PVX (P < 0.05). At exhaustion, plasma renin and aldosterone were not modified at HA compared with SL but were higher at RSL, whereas plasma atrial natriuretic factor was lower at HA. The present results suggest that PV contributes to the limitation of VO(2)(max) during acclimatization to HA. RSL-induced PVX, which may be due to increased activity of the renin-aldosterone system, could also influence the recovery of VO(2)(max).

Senescent human erythrocytes (RBC) are able to adhere to and be phagocytized by autologous monocytes in vitro to a greater extent than are young RBC. This adhesion and erythrophagocytosis of senescent RBC is inhibited by D-galactose, N-acetyl-D-galactosamine, their corresponding derivatives of bovine serum albumin, and lactose. On the other hand, D-glucose, D-mannose, L-fucose, N-acetyl-D-glucosamine, and their corresponding derivatives of bovine serum albumin are noninhibiting. The glycopeptides released by tryptic digestion of senescent RBC and purified on immobilized peanut agglutinin are the most effective inhibitors of both RBC adhesion and phagocytosis by autologous monocytes obtained from peripheral blood.There is a difference in sialic acid content between young and senescent erythrocytes (RBC). § This has suggested the possibility that in vivo senescence involves desialation of RBC with their subsequent sequestration from circulation (1, 33). The hypothesis has been supported by the observations that asialo-RBC (i) were rapidly sequestered from circulation (2-8) and (ii) readily gave rosettes with Kupffer cells and spleen monocytes in the absence of any additional serum factors (9,10). This postulated a lectin-like interaction between asialo-RBC and, indirectly, between senescent RBC and macrophages. Many investigators demonstrated that this interaction could be inhibited by simple sugars and oligosaccharides containing galactosyl residues (11)(12)(13). Further credence was given to this hypothesis with the isolation of a sialic acid-free glycopeptide from senescent RBC that was able to bind to spleen monocytes (14). Treatment of this glycopeptide with f3-galactosidase destroyed this property (14).An independent line of investigation demonstrated that senescent RBC have more bound IgG molecules compared to young RBC (15)(16)(17). The specificity of this IgG was characterized as anti-galactosyl (18). That raised the possibility that galactosyl residues are involved in the detection and sequestration of senescent RBC by autologous macrophages and that this might be mediated by both IgG and lectin-like receptors on the macrophages (19).In this study we demonstrate the ability to specifically inhibit the adhesion to and erythrophagocytosis of human senescent RBC by autologous blood monocytes. The most active inhibitor detected to date is a glycopeptide obtained from a tryptic digest of human senescent RBC (14). A preliminary report of these studies already has appeared. ¶ Senescent human RBC were separated from young RBC on the basis of differences in their density (20). Briefly, whole blood was centrifuged at 2000 x g for 120 min at 15°C; plasma and buffy coat were removed and discarded. The top 5% and the bottom 5% layers of RBC were collected by aspiration, and the effectiveness of this age-dependent fractionation was checked by measurement of the pyruvate kinase activity in the two fractions. The specific activity was 2.1 ± 0.5 times greater in the RBC from the top (young RBC) than in the bottom...

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