Award Date
12-1-2024
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Interdisciplinary Programs
First Committee Member
Thessa Hilgenkamp
Second Committee Member
James Navalta
Third Committee Member
Graham McGinnis
Fourth Committee Member
Bo Fernhall
Fifth Committee Member
Samantha John
Number of Pages
115
Abstract
BACKGROUND. Individuals with Down syndrome (Ds) are known to have low cardiorespiratory fitness, and it has been established that their low levels of cardiorespiratory fitness have a physiological cause. The influence of autonomic dysfunction has been demonstrated repeatedly, as chronotropic incompetence means individuals with Ds have lower (maximal) heart rate. Cardiorespiratory fitness is typically measured as peak oxygen uptake (V̇O2peak), and since oxygen uptake (V̇O2) is determined by cardiac output and the arteriovenous oxygen difference (according to the Fick principle), the attenuated cardiac response to exercise in individuals with Ds severely limits their cardiorespiratory capacity and exercise tolerance. However, recent research suggests other physiological factors also influence cardiorespiratory fitness in individuals with Ds. Individuals with Ds have reduced ventilation, lower oxygen uptake efficiency slope (OUES), impaired blood flow regulation, potentially limited peripheral oxygen extraction and suspected mitochondrial dysfunction. As such, the influence of the oxygen transport as a whole (i.e. the integration of the lungs/pulmonary system, cardiovascular system, and the muscles to transport oxygen from the air into the mitochondria for energy production) on cardiorespiratory fitness deserves further investigation in individuals with Ds. In addition, the rate at which oxygen uptake adapts to transitions in oxygen demand (e.g. at the onset of exercise) can contribute to exercise intolerance, as this adaptation occurs in a slowed, exponential fashion. This phenomenon is termed V̇O2 kinetics, and slower V̇O2 kinetics are associated with worse exercise tolerance. In the general population, the slowness of pulmonary V̇O2 kinetics is typically attributed to a delay in oxygen delivery (by the cardiovascular system; cardiac output (Q̇)) or mitochondrial oxygen utilization (in the muscles; muscle deoxygenation (Δ[HHb])). Investigating the kinetics of these three systems – i.e. pulmonary V̇O2, Q̇, and Δ[HHb] – simultaneously can provide novel insights regarding the role of the oxygen transport system in low cardiorespiratory fitness in individuals with Ds. In addition, the rate of V̇O2 kinetics might provide an alternative measurement of cardiorespiratory fitness in individuals with Ds, as these transitions in exercise intensity occur much more frequently than the intensity associated with V̇O2peak.AIMS. The overall aim of this dissertation was to determine how the oxygen transport system of individuals with Ds affects their exercise tolerance to further discover the physiological mechanisms causing low cardiorespiratory fitness in this population. The first specific aim towards this overarching goal was to determine the differences in V̇O2, Q̇ and [HHb] kinetics during submaximal exercise between individuals with and without Ds. The second aim was to determine the relationship between the speed of V̇O2 kinetics and V̇O2peak in individuals with Ds in order to investigate the potential of V̇O2 kinetics to predict cardiorespiratory fitness. The third aim was to investigate the relationship between the OUES and V̇E/V̇CO2 slope (which represents the efficiency of carbon dioxide clearance) by inspecting the influence of additional parameters of ventilation – pulmonary dead space, tidal volume, the ratio between pulmonary dead space and tidal volume (VD/VT ratio), and the partial pressure of carbon dioxide (PaCO2; the physiological driver of ventilation) – on the OUES and V̇E/V̇CO2 slope. METHODS. One cross-sectional study was designed to answer the individual specific aims. Healthy adults (18-35 years) with and without Ds completed a cardiopulmonary exercise test to determine V̇O2peak, VT, OUES, V̇E/V̇CO2 slope, and additional parameters of ventilation. Subsequently, participants completed a submaximal treadmill protocol at 80% of VT to determine the rate of V̇O2, Q̇, and [HHb] kinetics. The rates of VO2, Q̇ and [HHb] kinetics were compared between individuals with and without Ds, the correlation between the rate of V̇O2 kinetics and V̇O2peak was assessed for the total sample as for participants with and without Ds separately. The influence of parameters of ventilation on the OUES and V̇E/V̇CO2 was investigated by assessing differences between groups as well as comparing correlations. RESULTS. The rate of V̇O2 kinetics during submaximal exercise was not different between participants with and without Ds, but Q̇ kinetics were slightly slower in participants with Ds, and the [HHb] response was so markedly different that no kinetic parameters could be obtained in participants with Ds. No correlation was found between the rate of V̇O2 kinetics and V̇O2peak in participants with Ds, whereas this correlation was weak (but also not significant) in individuals without Ds. Participants with Ds had lower OUES than participants without Ds, but similar V̇E/V̇CO2. Participants with Ds also had smaller pulmonary dead space and tidal volume, while there was no difference found in PaCO2 and VD/VT ratio. OUES was not related to any of the parameters of ventilation in participants with Ds, while pulmonary dead space and tidal volume were significantly correlated to OUES in participants without Ds. Conversely, pulmonary dead space and tidal volume showed moderate correlations with VE/V̇CO2 in participants with Ds, but not in participants without Ds. CONCLUSIONS. The marked difference between the [HHb] responses of participants with and without Ds at the onset of exercise provide further indications that mitochondrial function is impaired in individuals with Ds, but could potentially also be caused by differences in blood flow regulation. The finding that V̇O2 kinetics were not different between participants with and without Ds, combined with the finding that within participants with Ds the rate of V̇O2 kinetics was not correlated to VO2peak, limits the utility of VO2 kinetics as an alternative measure of cardiorespiratory fitness in individuals with Ds, but the effect of training status on the rate of V̇O2 kinetics could use further investigation. Lastly, the finding that, despite the lower OUES found in participants with Ds, there was no difference in V̇E/V̇CO2 slope is most likely related to differences in ventilatory efficiency, but could also be another hint towards limited peripheral oxygen extraction and mitochondrial dysfunction in individuals with Ds.
Keywords
cardiorespiratory fitness; Down syndrome; submaximal exercise
Disciplines
Kinesiology | Medical Physiology | Physiology
File Format
File Size
1820 KB
Degree Grantor
University of Nevada, Las Vegas
Language
English
Repository Citation
Beck, Victor Duan Yi, "Oxygen Transport During Exercise in Individuals With Down Syndrome: The Role of Oxygen Uptake, Delivery and Utilization" (2024). UNLV Theses, Dissertations, Professional Papers, and Capstones. 5162.
http://dx.doi.org/10.34917/38330371
Rights
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