Increased hemoglobin oxygen affinity protects during acute hypoxia

2 Acclimatization to hypoxia requires time to complete the adaptation mechanisms that influence 3 oxygen (O2) transport and O2 utilization. Although decreasing hemoglobin (Hb) O2 affinity 4 would favor the release of O2 to the tissues, increasing Hb-O2 affinity would augment arterial O2 5 saturation during hypoxia. This study was designed to test the hypothesis that 6 pharmacologically increasing the Hb O2 affinity will augment O2 transport during severe hypoxia 7 (10% and 5% inspired O2) compared to normal Hb O2 affinity. Erythrocyte Hb O2 affinity was 8 increased by infusion of 20 mg/kg of 5-hydroxymethyl-2-furfural (5HMF). Control animals 9 received only the vehicle. The effects of increasing Hb O2 affinity were studied in the hamster 10 window chamber model, in terms of systemic and microvascular hemodynamics and partial 11 pressures of O2 (PO2s). Pimonidazole binding to hypoxic areas of mice heart and brain was also 12 studied. 5HMF decreased the P50 (PO2 at which the Hb is 50% saturated with O2) by 12.6 13 mmHg. During 10% and 5% O2 hypoxia, 5HMF increased arterial SO2 by 35 and 48% from the 14 vehicle group, respectively. During 5% O2 hypoxia, blood pressure and heart rate were 58% and 15 30% higher for 5HMF compared to the vehicle. In addition, 5HMF preserved microvascular 16 blood flow, whereas blood flow decreased to 40% of baseline in the vehicle group. 17 Consequently, perivascular pO2 was three times higher in the 5HMF group compared to the 18 control group at 5% O2 hypoxia. 5HMF also reduced heart and brain hypoxic areas in mice. 19 Therefore, increased Hb O2 affinity resulted in hemodynamics and oxygenation benefits during 20 severe hypoxia. This acute acclimatization process may have implications in survival during 21 severe environmental hypoxia when logistic constraints prevent chronic acclimatization. 22 23