The thesis investigated the effect of exercise on endothelial function (measured as flow-mediated dilation (FMD)) and triacylglycerol concentrations following the ingestion of a high-fat breakfast and lunch in adolescent boys. The validity of measuring lipid and lipoprotein concentrations from a capillary blood sample, and the reproducibility of the postprandial FMD and triacylglycerol concentration responses to the high-fat meals, was established. The effects of prior continuous moderate-intensity exercise (60 min walking at 60% V̇O₂peak), repeated very short duration sprints (40 x 6 s maximal effort cycle sprints) and accumulated moderate-intensity exercise (6 x 10 min running at 70% V̇O₂peak) on endothelial function and triacylglycerol concentrations in adolescent boys were then established across three studies, each consisting of two, 2-day main trials (control and exercise). On day 1, participants were either inactive or completed the prescribed exercise. On day 2, FMD and triacylglycerol concentrations were measured prior to, and following, ingestion of a high-fat breakfast and lunch. In each control trial FMD was reduced (signifying endothelial dysfunction), compared to fasting, by 20-32% and 24-33% following the high-fat breakfast and lunch. Following continuous moderate-intensity exercise, repeated very-short duration sprints and accumulated moderate-intensity exercise these reductions were only 8% and 10% (main effect trial, P = 0.002; main effect time, P = 0.023; interaction effect trial x time, P = 0.088), 2% and 5% (main effect trial, P = 0.012; main effect time, P = 0.004; interaction effect trial x time, P = 0.003) and 1% and 3% (main effect trial, P = 0.020; main effect time, P < 0.001; interaction effect trial x time, P = 0.014) respectively. The continuous moderate-intensity exercise and repeated very short duration sprints also significantly reduced the total area under the triacylglycerol concentration versus time curve by 22% (Control vs. Exercise; 12.68 (sem 1.37) vs. 9.84 (sem 0.75) mmol L-1 6.5h, P = 0.018) and 13% (Exercise vs. Control: 8.65 (sem 0.97) vs. 9.92 (sem 1.16) mmol L-1 6.5h, P = 0.023). The accumulated moderate-intensity exercise also reduced the total area under the triacylglycerol concentration versus time curve by 11%, but this reduction was not significant (Control vs. Exercise: 10.71 (sem 0.94) vs. 9.56 (sem 0.67) mmol L-1 6.5h, respectively, P = 0.183). The experimental evidence from these studies emphasise that exercise might offer an acceptable, non-pharmacological means of influencing CHD risk when individuals are young. The results of these studies can help shape future physical activity guidelines.

Although blood viscosity is an important component in determining vascular function, it is often assumed constant. Emerging evidence linking individual differences in viscosity to cardiovascular disease casts doubt on this assumption. The purpose of this study was to determine the contribution of whole blood viscosity to key measures of vascular function. To address this aim as comprehensively as possible, first, whole blood viscosity was compared with traditional risk factors for cardiovascular disease. Then flow-mediated dilation (FMD), carotid-femoral pulse wave velocity (cfPWV), and carotid artery compliance were calculated either with or without blood viscosity taken into account. Lastly, we tested whether the removal of blood viscosity could influence well-established associations between age and vascular function. Blood viscosity and vascular function were measured in 97 adults ranging in age from 18-63 years. No significant differences were observed between whole blood viscosity and traditional risk factors for cardiovascular disease. Whole blood viscosity was not significantly correlated with FMD, cfPWV, and carotid compliance. As expected, age was positively correlated with cfPWV (r=0.65, p<0.001) and negatively correlated with FMD (r=-0.21, p<0.05) and carotid compliance (r=-0.45, p<0.01). Even after controlling for viscosity, these relationships remained statistically significant (cfPWV r=0.65, p<0.001; FMD r=-0.24, p<0.05; carotid compliance r=-0.44, p<0.05). These results indicate that whole blood viscosity does not appear to significantly impact measures of vascular function and that the rationale for including whole blood viscosity in the calculation of vascular function remains weak. / text

abstract: Background. Despite research aimed at understanding the mechanisms of essential hypertension, instances of this condition continue to rise. Recent findings indicate that the administration of dietary nitrates, in the form of beetroot juice and other nitrate-rich vegetables, may offer anti-hypertensive effects in various study populations. Objective. This randomized, placebo-controlled, crossover trial sought to compare the effects of high-nitrate vegetable salads to the effects of low-nitrate canned vegetables on plasma nitrate/nitrite concentration, peripheral and central-aortic systolic and diastolic blood pressures, pulse wave velocity, and flow-mediated dilation. Methods. Healthy, post-menopausal women (n=5; 80% Caucasian; 52.6 ± 5.7 years) with mildly elevated blood pressure (mean blood pressure ≥ 115/70 mm Hg and < 140/80 mm Hg) were randomly assigned to ingest a fresh, high-nitrate vegetable salad or a low-nitrate vegetable medley, twice per day, for a total of 10 consecutive days. Given the crossover design of the trial, participants observed a two to three week washout period followed by reassignment to the opposite condition. Findings were considered significant at a p-value < 0.05, and Wilcoxon Signed-Rank tests compared mean differences between conditions. Results. Plasma nitrate/nitrite concentration was significantly higher following consumption of the high-nitrate versus the low-nitrate condition (p = 0.043). Conversely, the differences in peripheral systolic and diastolic blood pressures were not statistically significant (p = 0.345 and p = 0.684 for systolic and diastolic pressures, respectively) nor were the differences in central-aortic systolic and diastolic blood pressures statistically significant (p = 0.225 and p = 0.465 for systolic and diastolic pressures, respectively). Similarly, when comparing the effects of the high-nitrate condition to the low-nitrate condition, the difference in pulse wave velocity was not statistically significant (p = 0.465). Finally, flow-mediated dilation tended to improve following consumption of the high nitrate condition (p = 0.080). Conclusion. Twice daily consumption of a fresh, high-nitrate vegetable salad significantly increased plasma nitrate/nitrite concentration. Although the trial was underpowered, there was a trend for improved flow-mediated dilation. Finally, twice daily consumption of a fresh, high-nitrate vegetable salad did not significantly lower peripheral or central-aortic systolic or diastolic blood pressures or pulse wave velocity. / Dissertation/Thesis / Masters Thesis Nutrition 2017

Purpose The vascular endothelium is an influential contributor to vasodilation at rest, yet its role during peak exercise is relatively unknown. The purpose of this study is to determine if exercise leg blood flow during dynamic submaximal and maximal exercise is related to resting vascular endothelial function. Methods Nineteen subjects (aged 23 ± 0.57 yr) completed multiple assessments of vascular endothelial function including passive leg movement (PLM), rapid onset vasodilation, (ROV) and flow-mediated dilation (FMD). Peak muscle blood flow was assessed during single leg knee extension (KE) exercise. Doppler ultrasound of the femoral artery was utilized to assess muscle blood flow. Results Peak exercise blood flow was linearly related with microvascular endothelial function determined by PLM (P < 0.001) and ROV (P < 0.001). Normalizing muscle blood flow for quadriceps mass did not change this significant association. Individuals with high vascular endothelial function had greater muscle blood flow during KE compared to those with low endothelial function (P = 0.05). Post hoc analysis indicated a significant difference in blood flow between high and low endothelial function groups at 20 W, 30 W, and peak flow (P = 0.042, 0.048, 0.001, respectively). Conclusion Peak muscle blood flow during dynamic exercise is correlated with vascular endothelial function, as measured by PLM and ROV, accounting for between 30 to 50% of the variance in this relationship. These data support the hypothesis that endothelial function significantly contributes to the peak blood flow response during dynamic exercise.

No description available.

<p>Functional limitations place youth with cerebral palsy (CP) at an increased risk of physical inactivity and cardiovascular disease. The structure and function of the cardiovascular system of these adolescents has not been previously investigated. In the current cross-sectional study, endothelial function was assessed using flow-mediated dilation (FMD) in eleven adolescents with CP (age 13.2 ± 2.1 y) and compared to eleven healthy, age-and gender-matched control participants (12.4 ± 2.3 y). All participants with CP were ambulatory or ambulatory with assistive devices (lower leg brace) and classified as levels I-II according to the Gross Motor Function Classification System (GMFCS). Baseline arterial stiffness was examined through assessment of central and peripheral pulse wave velocity (cPWV, pPWV,) as well as carotid distensibility, a direct measure of central artery stiffness. A combination of B-mode ultrasound imaging and applanation tonometry was used to calculate carotid distensibility. Carotid intima-media thickness (IMT), a measure of vascular structure, was also quantified using B-mode ultrasound images and a semi-automated edge detection software program. cPWV was calculated using the distance (carotid to femoral via the subtraction method) and time delay between ventricular depolarization and the foot of the femoral waveform. pPWV was calculated from the femoral to dorsalis pedis artery using the distance between each site and time delay between the arrival of the foot of each corresponding waveform. Physical activity (PA) levels were assessed using a 7-day recall questionnaire. Anthropometric measurements as well as measures of resting systolic, diastolic and mean arterial blood pressures were similar in both groups. There were no group differences (p>0.05) in ivabsolute, relative or normalized FMD responses. Both groups also had similar values of carotid IMT as well as all measures of arterial stiffness including carotid distensibility, cPWV and pPWV (p>0.05). No group differences were found in the amount of time spent in light and moderate intensity PA; however, the control group participated in a significantly greater amount of vigorous intensity PA (CON: 196 ± 174 min. vs. CP: 38 ± 80 min). Pearson correlation coefficients with all participants revealed a significant positive relationship between age and cPWV (r=0.485 p=0.026) and negative relationship with carotid compliance (r=-0.436, p=0.048). These findings indicate that the arterial structure and function of youth with CP (GMFCS level I-II), examined in this study are not different from a healthy control group. Future research should include youth with CP of GMFCS levels III-V to gain further insight into the potential consequences of severe mobility impairments and functional limitations on levels of habitual PA and arterial health in this young, clinical population.</p> / Master of Science (MSc)

<p>The merits of low-volume high-intensity interval exercise (HIT) have been established in healthy populations; however, no studies have examined this exercise prescription in patients with coronary artery disease (CAD). The present thesis examined the acute and chronic effects of HIT in patients with CAD.</p> <p>The first study demonstrated transient improvements in brachial artery endothelial-dependent function, assessed using flow-mediated dilation (FMD), 60-minutes following a single bout of either HIT or moderate-intensity endurance exercise (END) in habitually active patients. The second study demonstrated no effects of training status on the acute endothelial responses to exercise; following 12-weeks of either HIT or END training. However, there was a significant reduction in endothelial-independent function immediately post-exercise, at both pre- and post-training, which requires further examination. The third study demonstrated comparable increases in fitness and resting FMD following 12-weeks of END and HIT, lending support to the notion that favorable adaptations are obtainable with a smaller volume of exercise. Lastly, the fourth study demonstrated no change in heart rate recovery following 12-weeks of END and HIT. However, pre-training heart rate recovery values reported by our sample were in a low risk range, which suggests training induced improvements may only be achievable in populations with attenuated pre-training values.</p> <p>The results of this thesis provide preliminary evidence supporting the use of HIT in patients with CAD. The findings of favorable transient and chronic improvements following HIT are notable, especially given the HIT protocol involves less time and work than END, which was modeled after the current exercise prescription in cardiac rehabilitation. Further investigations are necessary, including the assessment of additional physiological indices, the feasibility and adherence to HIT, the inclusion of CAD populations with co-morbidities including heart failure and diabetes, as well as other forms of HIT training including HIT combined with resistance training.</p> / Doctor of Philosophy (PhD)

Purpose: Evidence has accumulated to show that blood pressure variability (BPV) has a striking relationship with cardiovascular (CV) risk. Despite the mounting evidence implicating BPV as a CV risk factor, scant attention has been paid to: (1) the mechanisms by which high BPV confers greater CV risk; and (2) the efficacy of non-pharmacologic treatment modalities in the attenuation of BPV. In order to address these two unresolved questions, the purpose of this dissertation was twofold. The purpose of study #1 was to investigate the association between measures of short-term BPV (24-hour BPV) and long-term BPV (visit-to-visit BPV) with markers of endothelial health in a cohort of African Americans in order to determine if increased BPV may confer greater CV risk by eliciting injury to the endothelium. The purpose of study #2 was to investigate the effects of a 6-month aerobic exercise training (AEXT) intervention on visit-to-visit BPV and 24-hour BPV in the same cohort of African Americans in order to provide the first available data on the efficacy of a non-pharmacologic treatment modality in the lowering of BPV. Methods: We recruited 72 African Americans who were sedentary, non-diabetic, non-smoking, and free of CV and renal disease. Before and after a 6-month AEXT intervention, office blood pressure (BP) was measured at 3 separate visits and 24-hour ambulatory BP monitoring (ABPM) was conducted to measure visit-to-visit BPV and 24-hour BPV, respectively. Right brachial artery diameter was assessed at rest, during flow-mediated dilation (FMD), and after nitroglycerin-mediated dilation (NMD). Peak and area under the curve (AUC) were calculated as measures of FMD and NMD, and the FMD/NMD ratio was calculated as a measure of endothelial function normalized by smooth muscle function. Fasted blood samples were obtained and were analyzed for circulating EMPs expressed as CD31+CD42- and CD62E+ EMPs. Results: In study #1, participants with higher 24-hour diastolic BPV (DBPV) had significantly lower CD31+CD42- EMPs compared to participants with lower 24-hour DBPV. When categorized according to visit-to-visit DBPV, participants with higher visit-to-visit DBPV had a significantly lower FMD/NMD ratio, and significantly higher %NMDpeak and NMDAUCs compared to participants with lower visit-to-visit DBPV. When analyzed as continuous variables, 24-hour mean arterial pressure variability (MAPV) was inversely associated with CD31+CD42- EMPs visit-to-visit DBPV was inversely associated with the FMD/NMD ratio and positively associated with %NMDpeak and NMDAUC; and 24-hour DBPV was positively associated with NMDAUC. All associations were independent of age, gender, BMI, mean BP, and pulse pressure. In study #2 investigating the effects of AEXT in 33 participants who completed the study, 24-hour DBPV and 24-hour MAPV were significantly increased after AEXT. The increase in 24-hour DBPV was independent of changes in BMI, mean BP, and self-reported sleep time. Heart rate variability (HRV) derived from ABPM was associated with the changes in 24-hour DBPV and 24-hour MAPV. There were no significant changes in visit-to-visit BPV after AEXT. Conclusions: The results from study #1 provide evidence that BPV is associated with vascular health as endothelial function was decreased in participants with high visit-to-visit DBPV, while smooth muscle function was increased in participants with higher visit-to-visit and 24-hour DBPV. The findings from study #2 show that 6-months of AEXT do not elicit beneficial changes in BPV. The finding of an association between changes in 24-hour BPV with HRV could indicate, however, that changes in activity levels during ABPM, in part, contributed to the observed changes in 24-hour BPV. / Kinesiology

Purpose: Evidence has accumulated to show that elevated subclinical inflammation and impaired endothelial function has been associated with higher risk of cardiovascular disease (CVD). Despite data on these emerging risk factors, scant attention has been paid to: (1) the interactions of inflammation with endothelial function in relatively healthy African Americans; and (2) the efficacy of non-pharmacologic treatment modalities, such as exercise training, on inflammation and endothelial function. The aim of study 1 was to assess the levels of inflammatory markers, to assess the endothelial function in asymptomatic African Americans. The aim of study 2 was to determine the effects of six-months of exercise training on inflammatory markers and endothelial function in the same cohort. Methods: We recruited 79 African Americans who were sedentary, non-diabetic, non-smoking, and free of CV and renal disease. Before and after 6-month AEXT intervention, inflammatory markers (CRP, TNF-a and IL-6) were measured. Right brachial artery diameter was assessed at rest, during flow-mediated dilation (FMD), and after nitroglycerin-mediated dilation (NMD). Peak dilation was calculated as a measure of FMD and NMD, and the FMD/NMD ratio was calculated as a measure of endothelial function normalized by smooth muscle function. Fasted blood samples were obtained and were analyzed for the metabolic profile. Results: In study 1, the mean CRP for the group was 3.3 ± 0.3 mg/L which falls in the high-risk CRP category as per AHA/CDC guidelines. When divided into tertiles for CRP, low-risk (CRP 3 mg/L); VO2max was significantly higher in the low-risk category compared to average-risk category (P =0.004), and significantly higher in the low-risk category compared to high-risk category (P <0.001). Further, Cardiorespiratory fitness was significantly correlated with CRP (Figure. 1; r = -0.456, P <0.001) and BMI (r = -0.362, P = 0.002). CRP was correlated with BMI (r = 0.424, P <0.001). In a multivariable regression model that included age, gender, BMI, CVD risk factors (total cholesterol, triglycerides, HDL lipoprotein, LDL lipoprotein, plasma glucose, BP, and CRP), the following variables were significantly associated with fitness: fitness [B-coeff = -0.434 ± 0.05 (SE), P <0.001] independently predicted CRP. Fitness explained 22% of variance in CRP levels. In study 2, 6-month AEXT intervention significantly increased VO2max, (P=0.001), indicating that the prescribed exercise program may have been sufficient to elicit improvements in cardiovascular fitness. Significant reductions were observed for CRP (P =0.014). On repeated measures ANCOVA, the mean CRP values were significantly different (F (1,32) =6.703, P=0.014) between before vs. after training (Mean ± SEM; 3.1 ± 0.4 mg/L vs. 2.4 ± 0.4 mg/L), after adjusting for changed variables (BMI, mean BP and VO2max) as covariates. For endothelial measures, significant increase in endothelial function were observed for %FMDpeak (P =0.043) [Figure. 22] and FMD/NMD Ratio (P =0.047) increased post-AEXT. On repeated measures ANCOVA, the mean %FMD was statistically significantly different (F (1,16) =5.582, P=0.031) between before vs. after training (Mean ± SEM; 6.4 ± 2.6% vs. 9.4 ± 2.1%), after adjusting for changed variables (BMI, total-cholesterol and C-reactive protein) as covariates. Conclusions: The results from study 1 provide evidence of the prevalence of high levels of inflammation in the putatively healthy cohort of African Americans. When the group was categorized into tertiles for CRP and the cardio-metabolic, clinical and vascular profiles assessed, statistically significant differences, and rising trends were observed for CRP, body weight, BMI, BBF%, VO2max, SBP and DBP among the three CRP categories indicating a subclinical high cardiovascular risk profile in this cohort of putatively healthy population. Study 2, showed statistically significant improvements in inflammatory marker (CRP) and vascular measures (%FMDpeak, FMD/NMD Ratio and IMT); metabolic profile (triglycerides and FBS); clinical parameters (weight, BMI); cardiorespiratory fitness (VO2max). As we hypothesized, a marked reduction in CRP (-13.5%) post-AEXT was noticed, independent of change in(BMI, MAP and VO2max). Further, baseline CRP and BMI predicted change in CRP on regression analysis. Next, a marked increase in vascular measures, %FMDpeak (23.9%), FMD/NMD Ratio (25.4%) and IMT (-7.4%) were noticed independent of Ä(BMI, total cholesterol, MAP and VO2max). This may suggest: 1) the dominant anti-inflammatory role of exercise training. 2) that long-term exercise training improves clinical vascular measures in our cohort. / Kinesiology

Cardiovascular diseases (CVD) are the leading cause of death, and the underlying atherosclerotic process has its origin in youth. Physical activity lowers future CVD risk, however few adolescents achieve the recommended minimum amount of daily activity and interventions fail to meaningfully increase activity levels in this group. It is therefore essential to identify how small volumes of exercise can be optimised for the primary prevention of CVD. The purpose of this thesis is to identify the influence of exercise intensity on vascular health outcomes in adolescents, and to assess the efficacy of 2 weeks of low volume, high-intensity interval training on CVD risk factors in this population. Chapter 4 demonstrates that a single bout of high-intensity interval exercise (HIIE) performed one hour before a high fat meal elicits comparable reductions in postprandial lipaemia as a work-matched bout of moderate-intensity exercise (MIE) in girls. However, neither exercise attenuated postprandial lipaemia in the boys. Additionally, HIIE elicited a superior increase in postprandial fat oxidation and decrease in blood pressure, and this was sex independent. These findings are furthered in Chapter 5, which identified that accumulating HIIE, but not MIE, favourably modulates glycaemic control, postprandial blood pressure and fat oxidation in adolescents irrespective of sex. A high fat meal was included in Chapter 6 in order to impair vascular function via oxidative stress. Postprandial vascular function was preserved following MIE, but improved after HIIE, and these changes were not related to changes in postprandial lipaemia or total antioxidant status. Chapter 7 addressed the time course of the changes in vascular function post exercise, and identified that HIIE promotes superior changes in vascular function than MIE. Finally, Chapter 8 identified that 2 weeks of high-intensity interval training improved novel (endothelial function and heart rate variability), but not traditional CVD factors in adolescent boys and girls. However, most of these favourable changes were lost 3 days after training cessation. Thus, this thesis demonstrates that vascular health outcomes are positively associated with exercise intensity. Given that HIIE was perceived to be more enjoyable than MIE in Chapters 4, 6 and 7, performing HIIE appears to be an effectual and feasible alternative to MIE for the primary prevention of CVD.