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Theses and Dissertations

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Browsing Theses and Dissertations by Author "Bell, Christopher, committee member"

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    Acute ascorbic acid administration improves exercise hyperemia during rhythmic but not single contractions in aging humans
    (Colorado State University. Libraries, 2009) Simpson, Carrie Beth, author; Dinenno, Frank A., advisor; Earley, Scott, committee member; Bell, Christopher, committee member
    Age-related increases in oxidative stress are known to impair endothelium dependent vasodilation in older healthy humans. As a result, many researchers have speculated that endothelial dysfunction contributes to impaired muscle blood flow and vascular control during exercise. Further, elevations in oxidative stress and subsequent endothelial dysfunction could possibly explain our recent observations of impaired contraction-induced rapid vasodilation in older adults. Therefore, we directly tested the hypothesis that acute ascorbic acid administration would augment (1) rapid vasodilation in response to single muscle contractions as well as (2) the hyperemic response to sustained rhythmic contractions in older healthy humans, and that this would be due to improved endothelium-dependent vasodilation. In 14 young (22±1 yrs) and 14 healthy older men and women (65±2 yrs), we measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) responses to single, 1 second dynamic contractions at 10, 20, and 40% maximum voluntary contraction (MVC) before and after intra-arterial administration of ascorbic acid (AA). We also measured these variables during rhythmic handgrip exercise at 10% maximum voluntary contraction. After 5 minutes of steady-state exercise with saline, ascorbic acid (AA) was infused via brachial artery catheter for 10 minutes during continued exercise. For single contractions, prior to AA peak vasodilator responses to all contraction intensities were impaired ~35-50% in older adults (P<0.05), as were the immediate (1st cardiac cycle post contraction) vasodilator responses at 20 and 40% MVC (~50%; P<0.05). In contrast to our hypothesis, AA did not influence contraction-induced rapid vasodilation in either group (all NS). Regarding rhythmic handgrip exercise, FBF (~28%) and FVC (~31%) were lower in older vs young adults (P=0.06 and P<0.05) prior to AA. In young adults, AA administration did not significantly influence FBF and FVC, whereas FBF and FVC increased 30±4% in older adults at end exercise (P<0.05). AA did not influence vasodilator responses to sodium nitroprusside in either group, but significantly improved vasodilation to acetylcholine in older adults only (P<0.05). We conclude that endothelial dysfunction is not the primary mechanism underlying impaired contraction-induced rapid vasodilation with human aging; however acute AA administration increases muscle blood flow during dynamic exercise in older adults, which is likely due to an improvement in endothelium dependent vasodilation.
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    Role of the sympatho-adrenal system in the regulation of peripheral vascular tone in healthy aging humans
    (Colorado State University. Libraries, 2014) Richards, Jennifer Clarke, author; Dinenno, Frank A., advisor; Bell, Christopher, committee member; Tracy, Brian, committee member; Earley, Scott, committee member
    The following dissertation is comprised of a series of experiments with the overall aim of determining the role of the sympatho-adrenal system in the regulation of peripheral vascular tone in normal, healthy aging humans. Aging is associated with a reduction in aerobic capacity and elevated risk of cardiovascular disease. The decline in aerobic capacity could be a consequence of impaired O2 delivery, directly attributed to attenuated skeletal muscle blood flow. Attenuated skeletal muscle blood flow reflects a decline in the ability to adequately regulate peripheral vascular tone, either due to elevated vasoconstrictor signaling or decreased vasodilator signaling. Understanding the regulation of peripheral vascular tone and what leads to its decline with age could lend itself to the creation of treatments capable of improving oxygen (O2) delivery by increasing muscle blood flow. Net vascular tone is determined by the balance between vasodilator and vasoconstrictor tone within the vessel. With age, there is both a decrease in the production of local endothelium-dependent dilators as well as an increase in resting sympathetic nervous system (SNS) activity, which can lead to elevations in vasoconstrictor tone, potentially limiting blood flow to skeletal muscle. To better understand the role of the SNS in regulation of peripheral vascular tone with age, we can use established pharmacology and locally inhibit the sympatho-adrenal system and observe the net blood flow response during conditions that challenge the vascular system such as lowered O2 delivery (systemic hypoxia) and elevated peripheral O2 demand (exercise) in both young and older adults. We hypothesize that older adults will exhibit impaired regulation of peripheral vascular tone to both graded systemic hypoxia and graded handgrip exercise. Further, we hypothesize that the age-associated impairment is attributed to elevated vasoconstrictor tone mediated from the SNS. The primary findings of this dissertation are that older adults exhibit impaired regulation of peripheral vascular tone in response to physiological stressors (systemic hypoxia and handgrip exercise). Contrary to our hypothesis, the age-associated impairment was not directly attributed to elevated vasoconstrictor tone from the SNS and is likely due to attenuated vasodilatory signaling in older adults.
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    The influence of aerobic exercise on extracellular vesicles in obesity
    (Colorado State University. Libraries, 2021) Hayward, Brittany, author; Lark, Dan, advisor; Bell, Christopher, committee member; LaRocca, Tom, committee member; Kruh-Garcia, Nicole, committee member
    Purpose: Cardiometabolic disease is the leading cause of death in the United States. Metabolic syndrome describes several common metabolic parameters that increase risk of developing cardiometabolic disease(s). However, current risk factors of metabolic syndrome laid out by the American Heart Association have a poor correlation to cardiometabolic disease development. Prevention of metabolic syndrome and by extension cardiometabolic disease is perhaps the best method to combat morbidity and mortality. Exercise is one intervention that has proved not only to decrease the chance of developing chronic disease, but also reverse symptoms of those already experiencing metabolic dysfunction. Therefore, exercise could be the most potent treatment of metabolic syndrome and by extension cardiometabolic diseases. However, since exercise is a multisystemic and highly integrative stimulus, the mechanisms responsible for the beneficial adaptations of exercise are not yet fully understood. Extracellular vesicles are a heterogeneous subclass of excreted biologically active molecules that function to facilitate cell-to-cell communication. Extracellular vesicles are released during cardiometabolic disease and in response to exercise, but their relationship to metabolic health is poorly understood. Therefore, our objective was to examine if aerobic exercise alters the plasma concentration and/or size of circulating extracellular vesicles during both an acute bout of exercise and from exercise training. We then examined the relationship between extracellular vesicle plasma concentration and our subject's characteristics such as age, sex, body mass index, percent fat mass, peak oxygen consumption, among other physiological characteristics. Methods and Results: This study utilized plasma samples from subjects recruited from a recent clinical trial. Sedentary, overweight, but otherwise healthy men and women were invited to participate in a SGLT2 inhibitor exercise study. Thirty adults were recruited, fifteen adults were given an SGLT2 inhibitor and fifteen were on a placebo. Here, we examined only placebo treated subjects (N=14; 6/8 M/F; 23 ± 8 y; 30.6 ± 3.8 kg/m2; mean ± SD). Subjects underwent several baseline tests including maximal and submaximal exercise tests and body composition analysis. The subjects then participated in twelve weeks of a supervised aerobic exercise intervention. The baseline tests were repeated immediately after the intervention. Blood samples were taken during the submaximal standardized exercise test that was conducted before and after the exercise intervention. Extracellular vesicles were isolated and analyzed for their concentration and size distribution using nanoparticle tracking analysis. After excluding severely hemolyzed samples, six subjects were included in the extracellular vesicle analysis (3/3 M/F; 28 ± 11 y; 30.7 ± 3.4 kg/m2; mean ± SD). Our results indicate that the acute standardized exercise bout did not elicit changes in the concentration nor the size of extracellular vesicles. Additionally, when comparing samples pre- and post-exercise training, there was no change in extracellular vesicle concentration nor size. Collectively, these data insinuate an acute bout of submaximal exercise and/or exercise training do not increase circulating extracellular vesicle concentration in sedentary obese individuals. Linear regressions were performed, and Pearson correlation coefficients were reported in order to examine relationships between EV concentration and physiological factors. BMI, fat mass, percent body fat, lean mass, and oxygen consumption correlated with EV concentration in samples that were low to moderately hemolyzed (absorption <0.3 at 414 nm). However, the sample size was small and further investigations are needed. Conclusion: This study did not find any changes in extracellular vesicle concentration/size in untrained or trained subjects. However, several correlations between extracellular vesicle concentration and subject characteristics were found in sedentary and trained overweight but otherwise healthy adults. This study had several limitations that could have restricted our results, and therefore additional research is warranted to understand the connection between exercise and circulating extracellular vesicle characteristics.
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    The interaction between cycling cadence and substrate utilization in trained cyclists
    (Colorado State University. Libraries, 2021) Dippold, Victoria Mary Grace, author; Fahrner, Scott, advisor; Bell, Christopher, committee member; Hickey, Matthew, committee member; Orton, Christopher, committee member
    Currently, the optimal pedaling rate for road cycling endurance performance is not very well understood. It is known that muscle fiber recruitment patterns vary between low and high cadence rates. However, it is unclear whether different muscle fiber recruitment patterns stimulate different substrate utilization patterns between low and high cycling cadences. PURPOSE: We investigated if pedaling at a higher cadence at a submaximal work level results in a higher proportion of fat oxidation compared to cycling at the same intensity at a low cadence. In addition, we aimed at studying the optimal cadence for endurance road cycling and why well-trained and professional cyclists tend to pedal at higher rates. METHODS: Participants were trained, competitive cyclists and/or triathletes (VO2 max 60.4 ± 7.1 ml/kg/min, aged 24 ± 2.5 years, n = 11) living in Fort Collins, CO. All were training at least 8 hours per week and had participated in a competitive event in the past two years. Baseline testing consisted of a maximal consumption test (VO2 max test) that started at a low work level (50 – 100 watts) and increased by 25 watts every three minutes until exhaustion after which a verification bout was performed. From the VO2 max test, the first ventilatory threshold (VT1) was determined for each participant and served as the power output used during the cadence protocol that followed on a separate day. The cadence protocol entailed seven stages each lasting six minutes in length with a four-minute recovery period in between. Work rate remained constant during the cadence protocol while a different cadence was assigned randomly to each stage (60, 70, 80, 90, 100, 110 and freely chosen cadence (FCC)). RESULTS: Cadence had a significant effect on HR (estimated slope = 0.2634, SE = 0.032, p < 0.001), VO2 (estimated slope = 0.098, SE = 0.012, p < 0.001), RER (estimated slope = 0.0007, SE = 0.0001, p < 0.001), as well as absolute (estimated slope = 0.012, SE = 0.001, p < 0.001) and relative percentage of CHO utilization (estimated slope = 0.2696, SE = 0.053, p < 0.001. Cadence did not have a significant effect on absolute fat utilization, but it did have a significant effect on the relative percentage of fat utilization (estimated slope = -0.2283, SE = 0.053, p < 0.001. VO2, HR, and VE were minimized at 70 rpm while carbohydrate utilization was minimized at 60 rpm. FCC was found to be 89.8 rpm. Pairwise comparisons with FCC showed significant mean differences with respect to HR and VO2 between FCC and 70, 100, and 110 rpms as well as significant mean differences with respect to CHO utilization between FCC and 110 rpms. CONCLUSION: The increase in energy expenditure at higher cadences is not counterbalanced by a significant increase in fat oxidation, thereby resulting in a carbohydrate penalty at higher cadences. FCC is not solely chosen to limit metabolic cost or optimize substrate utilization. An optimal pedaling cadence may be one that allows the cyclists to maintain the highest wattage desired without a considerable amount of muscular fatigue while minimizing the consequent increased metabolic cost and CHO penalty.