The effects of prolonged hypoxia on respiration in man

Thesis

This thesis is concerned with the effects of prolonged hypoxia on ventilatory control in humans.

Chapter 1 reviews some of the relevant studies in animals and humans relating to this thesis.

Chapter 2 describes the experimental apparatus and technique employed in dynamic endtidal forcing using a computer-controlled gas-mixing system. It also details some of the basic analytical procedures used.

Chapter 3 describes the construction of a chamber for the long-term control of end-tidal gases. Preliminary testing showed this technique to be successful.

Chapter 4 documents the ventilatory response to 8 hours of isocapnic and poikilocapnic hypoxia. Ventilation rose dramatically during isocapnic hypoxia, but not during poikilocapnic exposure. The next chapter investigated the mechanisms responsible for these changes.

Chapter 5 assessed the changes in the ventilatory response to acute changes in hypoxia during the isocapnic and poikilocapnic hypoxic exposures of Chapter 4. Hypoxic sensitivity and hypoxia-independent ventilation increased during both hypoxic exposures and the changes were not significantly different between protocols. It was, therefore, proposed that hypoxia per se was responsible for the changes in ventilation during isocapnic hypoxia. Hypoxic sensitivity was thought to rise as a result of increased carotid body function. However, the mechanism responsible for the rise in hypoxia-independent ventilation was not clear.

Chapter 6 repeated the experiments of Chapters 4 and 5, but over a 48-hour period of hypoxic exposure and over the 48 hours of deacclimatization subsequent to the exposure. In addition, measurements of the eupnoeic ventilation and hypercapnic response were made. Ventilation continued to rise in the isocapnic exposure after 8 hours and also showed a gradual, but smaller, increase during the poikilocapnic exposure. Eupnoeic ventilation rose during both exposures and fell during deacclimatization towards the pre-exposure levels. These changes were similar in both protocols. The changes in hypoxic sensitivity and hypoxia-independent ventilation suggested that hypoxia was the major factor in determining the changes in respiratory control during prolonged hypoxia, in both poikilocapnia and isocapnia. Hypoxia was proposed to be the principal factor in the early stages of altitude acclimatization, and not the associated acid-base changes.

Chapter 7 describes the attempt to find a protocol to measure the hypoxic response (ventilation vs. Po2). This initial attempt was not successful, but, with modifications, the basic form of this protocol may provide a suitable test of the hypoxic response.

Chapter 8 presents a brief summary of the findings of this thesis and suggestions for future work.

Authors: Howard, LSGE

• DOI: 10.5287/ora-5rkam8mep
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford