Key result
Voxelotor administration for 14 days significantly increased arterial oxygen saturation at peak exercise in hypoxia from 71% to 81% (p<0.001), but did not improve peak oxygen consumption or exercise capacity.
Why the study?
Conditions reducing oxygen loading onto hemoglobin can impair exercise capacity, prompting examination of the impact of pharmacologically left shifting the oxygen-hemoglobin dissociation curve on arterial oxygen saturation and exercise capacity.
Does voxelotor improve arterial oxygen saturation and exercise capacity during maximal exercise in hypoxia in healthy individuals?
Does voxelotor improve arterial oxygen saturation and exercise capacity during maximal exercise in hypoxia in healthy individuals?
Absolute Event Rate: 81% vs 71%
p-value: p=<0.001
Pharmacologically increasing hemoglobin-oxygen affinity with voxelotor improves oxygen saturation in hypoxia but impairs exercise capacity in normoxia.
Voxelotor raises SaO2 without boosting capacity in hypoxic exercise; leaves open utility for high-altitude performance.
Stewart, Glenn M., Troy J. Cross, Michael J. Joyner, Steven C. Chase, Timothy Curry, Josh Lehrer-Graiwer, Kobina Dufu, Nicholas E. Vlahakis, and Bruce D. Johnson. Impact of pharmacologically left shifting the oxygen–hemoglobin dissociation curve on arterial blood gases and pulmonary gas exchange during maximal exercise in hypoxia. High Alt Med Biol . 22:249–262, 2021. Introduction: Physiological and pathological conditions, which reduce the loading of oxygen onto hemoglobin (Hb), can impair exercise capacity and cause debilitating symptoms. Accordingly, this study examined the impact of pharmacologically left shifting the oxygen–hemoglobin dissociation curve (ODC) on arterial oxygen saturation (SaO 2 ) and exercise capacity. Methods: Eight healthy subjects completed a maximal incremental exercise test in hypoxia (F I O 2 : 0.125) and normoxia (F I O 2 : 0.21) before (Day 1) and after (Day 15) daily ingestion of 900 mg of voxelotor (an oxygen/Hb affinity modulator). Pulmonary gas exchange and arterial blood gases were assessed throughout exercise and at peak. Data for a 1,500 mg daily drug dose are reported in a limited cohort ( n = 3). Results: Fourteen days of drug administration left shifted the ODC (p50 measured under standard conditions, Day 1: 28.0 ± 2.1 mmHg vs. Day 15: 26.1 ± 1.8 mmHg, p < 0.05). Throughout incremental exercise in hypoxia, SaO 2 was systematically higher after drug (peak exercise SaO 2 on Day 1: 71 ± 2 vs. Day 15: 81% ± 2%, p < 0.001), whereas oxygen extraction (Ca-vO 2 diff) and consumption (VO 2 ) were similar (peak exercise Ca-vO 2 diff on Day 1: 11.5 ± 1.7 vs. Day 15: 11.0 ± 1.8 ml/100 ml blood, p = 0.417; peak VO 2 on Day 1: 2.59 ± 0.39 vs. Day 15: 2.47 ± 0.43 l/min, p = 0.127). Throughout incremental exercise in normoxia, SaO 2 was systematically higher after drug, whereas peak VO 2 was reduced (peak exercise SaO 2 on Day 1: 93.9 ± 1.8 vs. Day 15: 95.8% ± 1.0%, p = 0.008; peak VO 2 on Day 1: 3.62 ± 0.55 vs. Day 15: 3.26 ± 52 l/min, p = 0.001). Conclusion: Pharmacologically increasing the affinity of Hb for oxygen improved SaO 2 during hypoxia without impacting exercise capacity; however, left shifting the ODC in healthy individuals appears detrimental to exercise capacity in normoxia. Left shifting the ODC to different magnitudes and under more chronic forms of hypoxia warrants further study.
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Stewart et al. (2021) studied Healthy subjects (n=11). Voxelotor vs. Baseline (Day 1, before drug administration) was evaluated on Peak exercise arterial oxygen saturation (SaO2) in hypoxia (p=<0.001). Voxelotor administration for 14 days significantly increased arterial oxygen saturation at peak exercise in hypoxia from 71% to 81% (p<0.001), but did not improve peak oxygen consumption or exercise capacity.
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