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Title: Cardiopulmonary responses to acute hypoxia and exercise in relation to the angiotensin converting enzyme insertion/deletion gene polymorphism
Author: Patel, Sameer
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2006
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The physiological response to environmental hypoxia encountered at high altitude has a wide range of cardiovascular and pulmonary effects. The insertion allele of the angiotensin converting enzyme (ACE) gene polymorphism has been found to be more prevalent in endurance athletes and is associated with beneficial anabolic and functional responses in muscle. Furthermore, the insertion allele of this functional genetic polymorphism has been associated with enhanced physical performance at altitude, as defined by the successful ascent of peaks over 4800 metres. This thesis examines the cardiopulmonary responses during exercise and hypoxia in order to elucidate any genotype dependent differences in cardiopulmonary response that could explain this observation. The main body of this work was carried out between August 1999 and September 2001. The studies involved 60 healthy subjects performing a maximal cardiopulmonary exercise test to determine ventilatory threshold (VT). At the second visit the subjects underwent a second set of steady state exercise tests, performed at 50% of the work rate attained at VT, under normoxic and hypoxic conditions (FiO2 12.5%). Metabolic and ventilatory measurements were made during tests and the changes between normoxic and hypoxic response during rest and exercise were analysed. A second smaller study examined cardiac output response during hypoxia and exercise using bioimpedance cardiography. These studies were performed simultaneously with the cardiopulmonary exercise tests and included 31 subjects. Similar analyses were performed on cardiac output variables between normoxia and hypoxia. The repeatability of the steady state cardiopulmonary exercise experimental protocol was verified by repeat testing and analyses. Bioimpedance cardiography measurements were validated against simultaneous measurements during pulmonary catheter studies and thermodilution cardiac output measurement. The results of the tests and the comparison of response demonstrated a larger increase in ventilation during exercise from normoxia to hypoxia in the insertion homozygous group. This was accompanied by a genotype dependent decrease in end-tidal carbon dioxide, suggesting a higher alveolar ventilation. There was no increase in oxygen saturations in the insertion homozygous group, which may have been due to the technical limitations of the oximeters. The cardiac output studies did not reveal any significant difference between genotype. The ventilatory study has demonstrated a response that may contribute to enhanced performance during prolonged hypoxic exposure, as experienced at high altitude.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral