Physiological Responses to Exercise in Hypoxia: The Effect of Cold-Air Exposure and Sex Differences

The effects of acute hypoxic exposure on physiological responses during exercise have been extensively studied in recent decades, given the growing number of individuals engaging in high-altitude (HA) activities for both training and recreational purposes. Understanding the impact of reduced oxygen availability on the physiological mechanisms involved in exercise responses is crucial for enhancing human tolerance to HA, thereby mitigating the health risks associated with this extreme environment. However, real-world HA scenarios often involve multiple stressors, with one of the most common being extremely low ambient temperatures. Despite the prevalence of such conditions, there is a scarcity of specific studies investigating the interaction between cold and hypoxic effects on exercising responses. This is largely due to the experimental, temporal, and practical challenges associated with such approaches. Additionally, many studies exploring the effects of acute hypoxic exposure on exercise physiology have predominantly focused on male subjects. This limitation complicates the understanding of whether tailored interventions based on biological sex are necessary to ensure the safest high-altitude exposure for both men and women. This doctoral thesis addresses these gaps by investigating the combined cold-hypoxic effects on whole-body exercise responses and examining the influence of biological sex on various aspects related to oxygen transportation within the organism at high altitudes. The research provides valuable insights into the intricate interaction between exercise and hypoxic stimuli while considering the real-world characteristics of HA exposure and its implications for all practitioners. In particular, Study 1 explores the independent and combined effects of cold and hypoxia on maximal, submaximal, and lactate threshold responses in trained male subjects. The findings indicate that both cold and hypoxia independently impact exercising responses, with the combination of the two stressors exhibiting additive effects on the majority of considered outcomes. Continuing from Study 1, Study 2 aims to investigate potential exacerbation effects of combined cold-hypoxic exposure on respiratory muscle fatigue (RMF) and exercise-induced bronchoconstriction (EIB). This study seeks to elucidate the relationship between exercising ventilatory responses and the pulmonary function and respiratory muscles work at simulated freezing altitudes. Results show that both respiratory muscle fatigue and exercise-induced bronchoconstriction are negatively affected by cold exposure, with no significant additional impairments related to the hypoxic stimulus, at least after high-intensity exercise of short duration. Finally, study 3 compares ventilatory responses, lung diffusion capacity, and cardiovascular adaptations in trained men and women during exercise in hypoxia. Similar responses to exercise during simulated high-altitude exposure have been observed in both sexes, suggesting no influence of biological sex on the variations in the functioning of the examined systems when circulating oxygen availability is reduced. This doctoral thesis and the data presented herein want to expand our understanding of hypoxic exercise and stimulate new research on this topic, minding the gap between experimental settings and real-world situations.