Ionizing radiation exposure during pregnancy raises concerns of potentially harmful effects for both the mother and the unborn child. Fetal programming involves permanent changes in offspring phenotype due to stress experienced in-utero. This phenomenon has been well characterized in cardiometabolic disorders such as hypertension. The effects of prenatal ionizing radiation exposure on offspring cardiovascular endpoints following birth were studied in a mouse model. Pregnant wildtype C57Bl/6J mice were irradiated on day 15 of pregnancy with whole-body 137Cs gamma radiation at nominal doses of 5, 10, 50, 100, 300 or 1000 mGy. Post-natal measurements of offspring weight and blood pressure were completed. In female pups, blood pressure was significantly increased at 300 mGy and heart rate significantly decreased at 1000 mGy. Female pups were growth restricted over the study period at 50, 100 and 1000 mGy. Growth restriction in male pups was only observed at the highest dose of 1000 mGy. Unintended effects on the study measures caused by transportation of pregnant mothers to the irradiation facility were most evident in male offspring with increased blood pressure and heart rate and decreased body size. These unintended effects caused by transportation may have been attenuated with the 10 mGy in-utero exposure. Overall, these results suggest that prenatal radiation effects in mice are both dose- and gender-dependent, with even fairly low doses demonstrating (potentially adaptive) effects. There is a need for further study to better characterize the mechanism of this response. / Thesis / Master of Science (MSc)

<p> Hypertension and reduced arterial distensibility are independent risk factors for cardiovascular disease. Previous research has found that isometric training reduces resting blood pressure (RBP) (Wiley et al. 1992; Taylor et al. 2003) yet the mechanisms responsible remain elusive. Improved arterial distensibility may contribute to this reduction in RBP. The purpose of the present study was threefold: 1) to replicate the RBP lowering effect of isometric handgrip (IHG) exercise; 2) to compare IHG and isometric leg press (ILP) based in their RBP lowering effects; and 3) to determine if central or peripheral arterial distensibility improved with IHG or ILP. The population examined was people whom were medicated for hypertension.</p> <p> RBP, as assessed by brachial oscillometry, and arterial distensibility, as assessed by Doppler ultrasound and applanation tonometry in the carotid, brachial and femoral arteries, were measured pre training, after 4 weeks of training, and post training. Participants performed unilateral IHG exercise (n=10) or ILP exercise (n=9) 3 times/week for 8 weeks at 30% MVC or acted as a non-exercising control group (n=5).</p> <p> Results indicated that the present study was unable to reproduce the RBP reductions noted in previous studies using IHG exercise. Also, the ILP exercise group did not experience reductions in RBP. Finally, neither central nor peripheral arterial distensibility improved in the IHG or ILP group when compared to the control group.</p> <p> Although these findings are contrary to our hypotheses one must consider that the control group examined contained very few subjects. This may have limited our ability to detect statistically significant changes in RBP and arterial distensibility.</p> / Thesis / Master of Science (MSc)

Transcranial magnetic stimulation (TMS) is commonly used to measure corticospinal and intracortical excitability in basic and clinical neuroscience. However, the effect of glucose on TMS-based measures is not well defined, despite a potentially impactful influence on precision and reliability. Here, a double-blinded placebo-controlled study was used to test the effects of glucose on two commonly used TMS measures: short-interval intracortical inhibition (SICI), and the area under the motor evoked potential recruitment curves (AURC). SICI and AURC are thought to reflect inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmission respectively. Healthy males (N=18) each participated in four sessions. Session 1 involved TMS familiarization and acquisition of an individualized blood glucose response curve. During sessions 2, 3 and 4, dependent measures were taken before (T0) and twice after (T1 & T2) drinking 300 mL of solution containing glucose (75 g), sucralose-sweetened placebo (control for sweetness) or plain water (control for time). The T1 and T2 measurements were started 5 minutes prior to the blood glucose peak observed during Session 1. Blood glucose and mean arterial pressure (MAP) were also monitored. Sucralose, but not water or glucose increased AURC and none of the treatments altered SICI. There was no association between blood glucose level and TMS measures, but in all three conditions MAP rose after consumption of the drink. There was a positive correlation between the rise in blood pressure and the relative increase in AURC at the higher stimulus intensities. Eleven participants returned for a fifth session to quantify the smallest detectible change in the AURC measurements and it was confirmed that significant changes were real while non-significant differences in measurement means fell within the range of expected measurement error. This study also suggests a relationship between corticospinal excitability and autonomic tone. Additional investigation is required to understand the mediating factors of this association. / Thesis / Master of Science (MSc)

Introduction: The homeostatic role of the endocannabinoid system (ECS) is mediated through the actions of endocannabinoids. Intake of exogenous cannabinoids found in Cannabis sativa alter the function of the ECS which may then impact other organ systems. Use of cannabis has been inconsistently linked to adverse cardiometabolic outcomes. Rates of cannabis use are high among patients with psychiatric conditions who are already at higher risk of cardiometabolic diseases when compared to the general population. Cannabis use patterns and cardiometabolic risk variables in this population need further study to clarify the links between use and outcomes. Methods: Patients with psychiatric conditions from the St. Joseph’s Healthcare Hamilton Hospital were enrolled into the Cannabis and Physical Health study. Sociodemographic data, medical history, cigarette use, and cannabis use patterns were collected. In addition, cardiometabolic profile data were collected including body mass index, blood pressure, lipids, and HbA1c. Multivariable regression analyses were conducted, and a Bonferroni correction applied. Results: This cross-sectional study enrolled 200 patients (female: n=86, 43.0%), 18 years of age and older. Among 79 cannabis users (female: n=34, 43.0%), the majority (n=53, 67.1%) consumed cannabis daily and had a diagnosis of a moderate cannabis use disorder (CUD; n=57, 72.2%, CUD score = 4.3 ± 3.4). Use of cannabis was initiated on average at 15.2 ± 3.5 years of age and used for an average of 13.5 ± 11.0 years. There was no association between cannabis use and cardiometabolic risk factors when adjusted for age, sex, psychiatric diagnosis, antipsychotic medication use, and cigarette smoking (P>0.006 for all outcomes). Conclusions: Our findings indicate that in this sample of patients with psychiatric diagnoses, patients who use cannabis had a similar cardiometabolic profile to non-users. Patterns of cannabis use highlight the importance of reducing cannabis consumption and preventing or slowing the progression of CUD in this population, as well as limiting adolescent exposure to cannabis. / Thesis / Master of Science (MSc) / The endocannabinoid system regulates several processes in the body via endocannabinoid signaling, and cannabinoids found in cannabis can change endocannabinoid system function. Cardiovascular events and changes in appetite have been noted with cannabis use, and this is especially important in some vulnerable populations at risk of increased cannabis use; one of these groups include patients with psychiatric conditions who tend to use cannabis but also already have an increased cardiometabolic risk. In this thesis, the relationship between cannabis use and cardiometabolic risk was examined in 200 patients, and patterns and determinants of cannabis use explored. Our results demonstrated that of the 79 cannabis users, most consumed cannabis daily, and had a moderate cannabis use disorder. On average, users began cannabis consumption at 15 years of age and for an average duration of 14 years. Moderate cannabis use was not related to cardiometabolic risk in these patients. Our data demonstrate the need to prevent or slow the progression of cannabis use disorder in these patients and the importance of reducing early exposure of adolescents to cannabis.

High sugar-sweetened beverage (SSB) intake and poor vitamin D status have both been associated with increased risk of elevated systolic blood pressure (SBP) in previous research. However, these associations have never been investigated in the same study population, leaving the question of a possible interaction uninvestigated. One potential mechanism for an interaction is that SSB intake may increase serum uric acid (UA) and UA may interfere with utilization of vitamin D. This study examined these relationships in a sample of men and women (n=2,875) aged 20-74 using data collected in the 2003-2006 NHANES survey. No statistically significant association was found between SSB intake and risk of elevated SBP (defined as SBP>120mmHg) in whole group analysis. In subgroup analysis by gender, women (n=1,550) showed a 68% (OR: 1.68, 95% CI: 1.12-2.50, p-value 0.011) increased risk of elevated SBP in the highest SSB intake quartile (mean intake of 3.27 servings/day) compared to the lowest (mean intake of 0.03 servings/day) after adjustment for age, race, BMI, alcohol use, physical activity, and smoking, but no association was found in men (n=1,325). A statistically significant association was found between 25(OH)D and SBP, with a 30% decrease in risk of elevated SBP (OR: 0.70, 95% CI: 0.55-0.90, p-value 0.005) for those in the highest serum 25(OH)D group (>75nmol/L) compared to the lowest (<50nmol/L) in the fully adjusted model. However, no association was found between SSB intake and serum UA. Assessing potential effect modification between SSB and vitamin D in their impact on blood pressure using a multiplicative term and stratified analysis did not provided evidence of an interaction effect.

The purpose of the current study was to test the hypothesis that chronic hypoxia associated with sleep-disordered breathing relates to abnormal Nitric Oxide (NO) production and vascular endothelial growth factor (VEGF) expression patterns that contribute to aberrancy of specific determinates of cardiovascular and cardiopulmonary function before, during, and after graded exercise. These patterns may further reflect pathologic alteration of signaling within the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt-1) transduction network. To this end, 7 medically diagnosed OSA patients (3 male, 4 female), mean age 48 years and 7 apparently healthy control subjects (3 male, 4 female), mean age 42 years, underwent baseline venous blood draws and maximal bicycle ergometry. Mononuclear cells isolated from peripheral blood were utilized as reporter cells for measurement of VEGF, Akt-1, hypoxia inducible factor-1 alpha (HIF-1 alpha), and vascular endothelial growth factor receptor-2 (VEGFR2) gene expression by redundant oligonucleotide DNA microarray and real-time PCR technologies. Circulating angiogenic progenitor cells expressing VEGFR2 were profiled by flow cytometry. Plasma and serum concentrations of VEGF, nitrates/nitrites, catecholamines, and dopamine were measured by enzyme-linked immunosorbent assay (ELISA) and high performance liquid chromatography (HPLC). Arterial blood pressure, cardiac output, oxygen consumption and total peripheral resistance were determined at Baseline, 100W, and peak ergometric stress by standard techniques. There were no apparent differences (p < .05) observed in biochemical markers relating to vascular function and adaptation including, serum nitrates/nitrites, norepinephrine, dopamine, and plasma VEGF. No differences were found relative to cardiac output, stroke volume, cardiopulmonary or myocardial oxygen consumption, expired ventilation, heart rate, arteriovenous oxygen difference, total peripheral resistance, and mean arterial pressure. Due to methodological issues related to the redundant oligonucleotide DNA microarray and real-time PCR gene expression analyses, results of these experiments were uninterpretable. Thus, the research hypothesis was rejected. Conversely, significant (p < .05) differences were observed in waist: hip ratios, recovery: peak systolic blood pressure ratio at 1 minute post-exercise and %VEGFR2 expression. OSA was associated with elevations in both waist: hip ratios and recovery: peak systolic blood pressure ratio at 1 minute post-exercise as well as significant depression of %VEGFR2 profiles. Moreover, significant negative correlations were found regarding waist: hip ratios and %VEGFR2 expression (r = -.69;p =.005) and recovery: peak systolic blood pressure ratio at 1 minute post-exercise and %VEGFR2 expression (r = -.65;p =.01). These findings did not provide evidence that NO-dependent vasoactive mechanisms are suppressed nor did they support the supposition that angiogenic mechanisms are pathologically activated in sleep-disordered breathing. / Ph. D.

This experiment was primarily designed to identify higher cortical correlates of cardiovascular arousal. Low- and high-hostile, right-handed, undergraduate men were identified using the Cook Medley Hostility Scale (CMHS). All participants (N = 30) completed the cold pressor paradigm. Cardiovascular (heart rate, systolic blood pressure, and diastolic blood pressure) and electroencephalographic (beta magnitude) data were collected before and after the stressor. As predicted, high-hostiles showed greater increases of heart rate and systolic blood pressure to the stressor relative to low-hostiles. The primary findings of this research include significantly greater beta magnitude recorded by the T3, relative to F7, electrode among low-hostiles. This may suggest that low-hostiles experience left-frontal disinhibition of left-temporal regions, thereby strengthening cardiovascular regulation during the cold-pressor stress. In addition, irrespective of condition, high-hostiles evidenced significantly greater beta magnitude at regions corresponding to the F7 and F8 electrodes. This perhaps suggests that high-hostiles have a relative inability to increase their rostral modulation of posterior systems related to cardiovascular activity/regulation. Low- and high-hostiles did not, however, evidence reliable differences in their ability to monitor cardiovascular arousal to the cold-pressor stress. Findings are discussed in terms of a systems approach, and pertinent future research is recommended. This research did not support the prominent neuropsychological theories of cardiovascular regulation proposed by Heilman et al. (1993) and Tucker and Williamson (1984). Rather, the results may suggest that right- and left-cerebral mechanisms may be primarily responsible for sympathetic and parasympathetic cardiovascular arousal, respectively. / Ph. D.

Forty-six employees of an industrial bearing plant volunteered to participate in a workplace hypertension program. The purpose of this study was to lower hypertensive employees' blood pressure by having plant supervisors educate the employee in an eight-week hypertension program on his or her high blood pressure. This was done in an effort to aid employees in the management of their blood pressure, as well as to provide a source of emotional support within the plant. Subjects were randomly assigned to an experimental or control group. Supervisors of each hypertensive subject were given educational instruction on high blood pressure and variables related to hypertension. Supervisors also were given specific weekly assignments to convey to their subjects. Pretest and posttest measurements were made on blood pressure and knowledge concerning blood pressure. At the end of the eight-week intervention, a significant decrease in systolic blood pressure was seen in the experimental group with a 16 mm.Hg. drop (p < .05). There was no significant difference (p > .05) between the two groups on diastolic pressures, with both groups dropping to within the guidelines recommended by the American Heart Association (1987). Subjects in the experimental group scored higher on their knowledge of blood pressure than did subjects in the control group (p < .01). The results of this study indicate that a hypertensive educational intervention program may produce positive changes in employee blood pressure responses. / Master of Science

Abrupt decreases and increases in systolic arterial blood pressure produce baroreflex mediated shortening and lengthening, respectively, of the R-R interval. This phenomenon, otherwise known as the cardivagal baroreflex, is best described by the sigmoid relationship between R-R interval length and systolic blood pressure. The linear portion of this relationship is used to derive the slope or gain of the cardiovagal baroreflex. Importantly, lower levels of cardiovagal baroreflex have been associated with poor orthostatic tolerance and an increased cardiovascular disease-related mortality. The most commonly used and accepted technique to assess cardiovagal barorelex gain is the modified Oxford techinique. Bolus injections of sodium nitroprusside followed by phenylephrine HCL are used to decrease and raise blood pressure ~15 mmHg, respectively. The baroreflex control of the cardiac vagal outflow can then be assessed by the relation of the R-R interval to systolic blood pressure. However, the modified Oxford technique does not always reveal the nonlinear nature of baroreflex relations. The reasons for this has been unclear. Thus, analysis of baroreflex gain when nonlinearities are not revealed is problematic. Five classifications of baroreflex trials have been identified: acceptable, threshold-heavy, saturation-heavy, linear-heavy, and random trials. A new method of gain estimation was developed that combines the strengths of the current methods of gain estimation with the knowledge of the classifications of baroreflex trials. Using this method, cardiovagal baroreflex gain assessment can be maximized if threshold-heavy, saturation-heavy, and random trials are filtered out of the analysis and the manual method is used to estimate gain on the remaining trials. In addition, a link seems to exist between the variability of delta and the variability in baroreflex gain between different subjects. / Master of Science

Objective: This study explored the relationship of risk perception with change in health behaviors and social cognitive theory (SCT) constructs. Additionally, this study evaluated the feasibility, utility, and practice of self blood pressure monitoring (SBPM). Design: Adults with prehypertension, ages 45-62 (N = 23) completed the Risk Perception Survey for Developing Hypertension (RPS-DH) and Health Belief Survey (HBS) during the screening portion of Dash-2-Wellness (D2W), a lifestyle modification intervention. Participants were randomized into one of two treatment groups, Dash-2-Wellness Plus (D2W Plus) or Dash-2-Wellness Only (D2W Only). Both groups were given dietary counseling regarding the DASH diet and encouraged to monitor their physical activity using a pedometer. The D2W Plus group also engaged in SBPM. Results: Moderate correlations were found between composite risk perception and change in step count (r = -.47, p = .03), and change in systolic blood pressure (r = .42, p = .04). Baseline risk perception was not related to SCT variables, with few exceptions. High levels of compliance (M = 90.36%, SD = 12.62) were reported for SBPM. Conclusions: Findings indicate that risk perception may play a limited role in motivating change in continuous health behaviors, particularly in asymptomatic conditions. Additionally, the nature of the risk reduction offered by the behavior may also influence its association with risk perception as a motivator for change. Findings suggest that SBPM is a feasible and useful behavior. Reports regarding positive affect and ease of machine use in regards to this behavior may increase the likelihood of regular compliance. / Master of Science