Adjusting attitudes about altitude: novel approaches to promote human performance in high-altitude

Abstract

Military personnel frequently operate in environmental extremes, such as high-altitude, without adequate time for acclimatization. Altitude mediated decrements in human physiological function jeopardize mission success and personal safety. The following dissertation describes three experiments directed at the identification of non-traditional, military specific approaches to promote human functional performance in high-altitude. The specific aims of the following experiments were: 1) to compare the difference in time trial performance in normoxia and hypoxia following oral administration of a placebo, a non-specific phosphodiesterase inhibitor/adenosine receptor antagonist (Aminophylline), a carbonic anhydrase inhibitor (Neptazane), or the combination of Aminophylline and Neptazane; 2) to assess endurance exercise performance in hypoxia following an intravenous infusion of glucose with and without prior sympathetic nervous system inhibition (clonidine); and 3) to determine endurance exercise performance in hypoxia following a high-carbohydrate meal with and without prior/concurrent administration of an oral insulin sensitizer (metformin) and to compare hypoxic endurance exercise performance with endurance exercise performance in normoxia following the same meal. When compared with normoxia, hypoxia attenuated endurance exercise performance in these experiments. In experiment 1, we found that concomitant administration of Aminophylline and Neptazane attenuated the hypoxia-mediated deficit in endurance exercise performance compared with placebo. Neither Aminophylline nor Neptazane alone ameliorated this decrement. In experiment 2, prior clonidine administration attenuated the cardiovascular response to hypoxia assessed by heart rate and blood pressure responses at rest but did not deleteriously impact endurance exercise performance in hypoxia. Finally, the preliminary data from experiment 3 suggest metformin improved the metabolic response to a high-carbohydrate meal in hypoxia, and potentially augmented skeletal muscle glycogen synthesis. Endurance exercise performance was unaffected in hypoxia following metformin administration. Collectively, the data from these experiments suggest these pharmacological treatments, compatible with military specific demands, effectively promote human physiological function in high-altitude.