INTERACTIONS BETWEEN HB, MG, DPG, ATP, AND CL DETERMINE THE CHANGE IN HB-O2 AFFINITY AT HIGH-ALTITUDE

Ascent to high altitude (HA) causes an increase in erythrocyte 2,3-diphosphoglycerate (DPG) and standard P(O2) at 50% 02 saturation, P(CO2) 40 Torr, and blood pH 7.4 (P(50,st)). We studied the early phase of acclimatization to HA of mountaineers without and with a history of HA pulmonary edema. Tests were performed before ascent and after arrival at HA (4,559 m), approximately 22 h after the departure from low altitude (HA1) and on the following 3 days at HA (HA2-HA4). We investigated the relation between changes in DPG and P(50,st,) since at moderate altitude P(50,st) increases more rapidly than DPG, indicating that other factors may contribute to the change in P(50,st). Combined effects of interaction between allosteric effectors of hemoglobin (Hb) (DPG, ATP, Cl) and Mg, which competes with Hb for DPG and ATP binding, might explain that phenomenon. Therefore concentrations of liganded Hb species were calculated from the total erythrocyte concentrations of the ligands by use of published binding constants and were related to changes in Hb-02 affinity. P(50,st) increased at HA by approximately 4.5 Torr; the concentration of total DPG and ATP increased by 28 and 19%, respectively. Whereas P(50,st) reached a plateau already at HA1, the concentration of DPG reached its highest value at HA4. The erythrocyte Cl concentration decreased, whereas cellular Hb and Mg concentrations increased slightly. The sum of concentrations of all liganded Hb species increased, reaching 79% of its total change within 22 h after ascent; this can mainly be attributed to the change in the concentration of Hb[DPG] (+77% of total increase). The concentrations of Hb[DPG] and Hb[ligand] but not that of total DPG parallel the change in P(50,st) at HA, which can now be attributed to the combined effects of all studied ligands.