Biomedical Physiology and Kinesiology - Theses, Dissertations, and other Required Graduate Degree Essays

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Elevated blood pressure and hypertension in South Asian children: A mixed-methods analysis exploring associated factors and behavioural influences

Author: 
Date created: 
2019-10-16
Abstract: 

The overarching objective of this PhD thesis was to develop a better understanding of how broad-based (physiological, lifestyle, social and cultural) factors, influence blood pressure (BP) in South Asian children in Canada. This was done using a mixed-methods approach that included: a systematic review which informed the direction of the study; multivariate regression analyses to estimate the correlates of BP and hypertension in South Asian children; receiver operating characteristics curve analysis to estimate the validity of adiposity metrics in estimating adverse risk of hypertension in South Asian children, including the appropriate risk thresholds; and semi-structured qualitative interviews to explore attitudes towards healthy behaviours in South Asian children and their parents. From the systematic review, I identified a range of physiological, social and lifestyle factors that were associated with elevated BP and hypertension in children. These variables were subsequently investigated in a sample of 762 South Asian children in Canada. The results suggested that for these children, physiological variables provided better explanatory capacity regarding the risk of elevated BP and hypertension than social or lifestyle factors. Age, sex, BMI z-score, heart rate and weight accounted for 30% of the variance of sBP z-score, while age, BMI z-score, heart rate and daily fast food intake accounted for 23% of the dBP z-score variance. The prevalence of hypertension was found to be high at 12%. The area under the curve (AUC) values for the adiposity measures for boys and girls ranged from 0.74–0.80, suggesting that the adiposity measures were fair in their ability to estimate hypertension risk. Yet, sex-stratified cut-offs associated with adverse risk of hypertension for South Asian boys and girls suggested that these children might be at high risk of hypertension at levels of adiposity considered normal. Last, my interview findings documented the range of influences on healthy behaviour in South Asian children and their parents including school, peer, social media and cultural dynamics. Taken as a whole, my thesis provides vital information for healthcare practitioners in identifying and treating at-risk South Asian children, and for public health practitioners and policymakers in informing the development of effective intervention strategies aimed at preventing hypertension and CVD risk in this population.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Scott Lear
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) Ph.D.

Pediatric syncope diagnosis and management: Validation of continuous blood pressure monitoring and alternatives to 24-hour urine sodium sampling

Author: 
Date created: 
2019-10-10
Abstract: 

Syncope, or fainting, is common and has a devastating impact on quality of life. Diagnosis and management of syncope is challenging. In pediatric populations the current diagnostic gold standard, a tilt test, cannot be safely or properly performed, because the necessary non-invasive beat-to-beat blood pressure monitoring is not validated for children. In addition, low sodium intake is common in syncope patients, and salt supplementation is recommended. However, standard assessments of sodium from urine collections are difficult and unpleasant. This thesis demonstrated that: (i) continuous non-invasive finger blood pressure monitoring provides a novel, comfortable, and accurate approach for use in children compared to an intra-arterial catheter, (ii) Quantab test strips provide a valid alternative to flame photometry for the determination of 24-hour urine sodium levels, and corrected spot sample averages offer an acceptable and convenient alternative to 24-hour urine sampling. These advancements in diagnostic tools for syncope will enhance quality of life for affected individuals.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Victoria Claydon
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Evaluation of an exercise program delivered prior to hemodialysis

Author: 
Date created: 
2019-06-25
Abstract: 

Although it is broadly accepted that exercise offsets poor health outcomes experienced by hemodialysis patients, incorporating exercise into patients’ lives remains a challenge. This study aimed to (1) determine the effects of a pragmatically-designed exercise program on physical performance, mental health, and quality of life of hemodialysis patients, and (2) explore patient and staff experiences with the exercise program at five dialysis units. Intervention participants were offered a thrice-weekly, 12-week exercise program at the unit prior to hemodialysis. Health-related quality of life (EQ-5D-5L Index Value) improved significantly for the exercise participants compared to control. Physical performance (Short Physical Performance Battery) and mental health (Center for Epidemiological Studies Depression Scale-Revised) did not change significantly. The majority of participants and staff reported positive feedback and benefits from the exercise program. In conclusion, a pragmatically-designed exercise program delivered before hemodialysis improved patients' quality of life and was well-received by patients and staff.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Dawn C. Mackey
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

The effect of sudden drop in partial pressure of oxygen during ascent on heart function

Author: 
Date created: 
2019-08-12
Abstract: 

Background: Cardiovascular disease is the second leading cause of diving deaths. Scarcity of 12 lead ECG recordings during dives leaves many questions unanswered about cardiac function during ascent. I hypothesized that decreased oxygen partial pressure (PpO2) initiates cardiac arrhythmia on ascent. I examined heart rate variability (HRV), rhythm and circulating markers of cardiac damage in the blood in response to submersion, increased pressure and reduction in the partial pressure of oxygen during the ascent. Methods: Experiments were performed in the wet pot of the hyperbaric chamber. Participants (N=19) were occupational and scientific divers, age 39.3 years, BMI 26.5 kg/m2, 3 females. Each completed two dives in a drysuit while swimming in 8oC water outfitted with a 12 lead ECG holter recorder. A 30-minute swim was performed at ambient pressure followed by a dive to 5 atmospheres absolute (ATA) with a direct ascent to surface pressure. The experimental exposure held the PpO2 at 1.0 ATA for the ascent. Blood samples were drawn at baseline, immediately after the dive and one-hour post dive. ECG analysis was performed for 5 epochs of 5 minutes each. Results: Diving increased heart rate and decreased HRV (p<0.05). The change in heart rate variability time domain was increased on ascent with oxygen clamping over the control (P=<0.004). Diving increased markers of cardiac vagal tone (P=<0.02) and decreased markers of sympathetic tone (P=<0.003). Diving caused QTc prolongation, particularly in the control (P=0.021) on ascent. No ST depression was observed, and ST elevation was present in the anterior leads with no differences between epochs or conditions. Diving increased the number of atrial ectopics (PAC) particularly with oxygen clamped on ascent (P=0.002). There was no troponin (cTnI) or significant change in pH or Lactate however there was a significant increase in B-Type natriuretic peptide (BNP) production with the oxygen clamped on ascent (P=<0.0001). Discussion: This is the first study to examine the effect of submersion and diving on HRV using 12 lead ECG while exercising in a controlled study, and unlike previous studies without exercise I saw an increase in HR and a significant decrease in heart rate variability. This agrees with the effect of exercise alone. The effect of clamping oxygen on the ascent eliminated the reduction of HRV from control. Submersion and diving both increase markers of cardiac vagal tone unlike the effect of exercise. Markers of sympathetic tone were decreased during submersion but not during the 5 ATA dive. This suggests an autonomic conflict not observed when no exercise is present during a dive. The ST segment elevation showed the typical “early repolarization syndrome” of young, athletic, healthy, males with physically demanding jobs. Under conditions of high oxygen pressure an increase in the QT interval from baseline was observed along with a significant increase in PACs and BNP levels. Its relation to the observed PAC’s and QTc is unclear.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Peter Ruben
Michael Koehle
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Detection of motor-learning related neuroplasticity in white matter using functional MRI techniques

Author: 
Date created: 
2019-06-25
Abstract: 

Neuroplastic change has been investigated extensively in the brain's grey matter, focusing largely on activity dependent modulation of synapses. However, new work has supported the presence of neuroplastic change in white matter through modulation of myelination, or other mechanisms. Though structural neuroimaging studies have detected neuroplastic change in white matter, we currently lack MRI based methods of tracking functional changes in the white matter in vivo. To address this gap in the literature, we investigated the patterns of BOLD fMRI activation in white matter. Participants completed two weeks of motor training, using both their dominant and non-dominant hand, in order to stimulate neuroplastic change, and fMRI activity was compared between timepoints, revealing white matter activation in the group level at each timepoint. No difference in amplitude of activation was detected at the group level, but a change in the temporal characteristics of the hemodynamic response was noted in the pre/post training contrast for the non-dominant hand.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Ryan D'Arcy
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

A human iPSC-CM model for type 1 catecholaminergic polymorphic ventricular tachycardia (CPVT1)

Author: 
Date created: 
2019-07-05
Abstract: 

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating, heritable cardiac arrhythmia and often a cause of sudden cardiac death. Greater than 50% of cases of CPVT are due to genetic variants in the cardiac ryanodine receptor (RyR2). CPVT-associated RyR2 variants often result in gain-of-function phenotypes, producing a dominantly inherited and difficult to treat disease. Human induced pluripotent stem cells (hiPSCs) have been used to generate patient-specific hiPSC-derived cardiomyocytes (hiPSC-CM) to study CPVT phenotypes and pharmacological approaches, however generating hiPSCs from patients is low through-put and lacks true isogenic controls. Therefore, this thesis aimed to use CRIPSR/Cas9 genome-editing technology to generate hiPSC cells lines harbouring a CPVT-associated variant. Genome-edited hiPSCs were differentiated into 2D tissue-like monolayers of hiPSC-CMs, and voltage and calcium dynamics were measured. This thesis indicates that CRISPR/Cas9 is a useful technology for studying CPVT in an in vitro human model, and that the R417L mutant disrupts hiPSC-CM calcium handling.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Glen Tibbits
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Molecular determinants of voltage sensor movement and its transduction to pore opening by the S4-S5 linker in the hERG potassium channel

Author: 
Date created: 
2019-04-15
Abstract: 

The hERG potassium channel, found in cardiac tissues, is an important contributor to cardiac repolarization. Loss of function of hERG channels is associated with long QT syndrome, a condition linked to sudden cardiac death. Unlike other Shaker-like voltage-gated potassium (Kv) channels, hERG channel activation (opening) and deactivation (closing) kinetics are unusually slow and this is critical to their unique role in repolarization. Despite this, the mechanistic basis for slow gating kinetics in hERG remains unclear. In Shaker-like Kv channels movement of the voltage sensor upon depolarization is mechanically transduced by the alpha-helical S4-S5 linker to S6 pore opening. Given the unique gating properties of hERG channels, the details of voltage sensor movement and its coupling with the S6 activation gate are of significant interest. My thesis examines the mechanistic basis to S4 voltage sensor movement and its transduction to pore opening. In my first study, I use a flexibility removed hERG mutant (G546L) to examine the role of S4-S5 linker flexibility in the activation gating of hERG channels. The flexibility removed channels are stabilized in the open conformation and when flexibility is reintroduced elsewhere in the S4-S5 linker there is a restoration of WT-like activation gating. This suggest flexibility of the S4-S5 linker regulates hERG channel closed-state stabilization. I then examine the role of the S4 voltage sensor and the S4-S5 linker in slow deactivation. To do this I examined charge conserving mutations within the S4 voltage sensor, single glycine substitutions in the S4-S5 linker and an N-terminally deleted channel. These data suggest that the intrinsic relaxation transition of the voltage sensor causes the slow deactivation kinetics characteristic of hERG. They also suggest that both the S4 voltage sensor and S4-S5 linker are attractive targets for hERG modifying compounds. In my final study, I investigate the utility of the adult zebrafish whole heart translational model in the screening of hERG modifying compounds. Using the oocyte expression system, I conducted a pharmacological characterization of the zebrafish paralog of hERG, zkcnh6a, and using optical mapping of the zebrafish whole heart, I show that this model may serve as a valuable tool in the screening of hERG modifying compounds.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Thomas Claydon
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) Ph.D.

Cardio-postural control and cerebral autoregulation in older adults after ischemic stroke

Author: 
Date created: 
2019-04-09
Abstract: 

Acute ischemic strokes are a common cause of death within the world’s population. Older adults affected by cerebral infarctions, often experience orthostatic hypotension which can be associated with autonomic dysfunctions. By using a method to identify the bi-directional relationship between cardiovascular control and postural control, as well as cerebral autoregulation, new insight into orthostatic hypotension associated with ischemic stroke can be provided. This thesis compared acute stroke patients with healthy controls as well as females and males to examine the relationships within the cardio-postural model and included the new aspect of involving the cerebral autoregulatory system and their correlation. It was hypothesized that stroke patients show impairment within the autonomic system and the cerebral autoregulation. A decrease in cardiovascular baroreflex, muscle-pump baroreflex, and cerebral autoregulatory impairment was shown in stroke patients compared to the healthy controls. Furthermore, the impairment was greater in female stroke patients.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Andrew Blaber
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Implantable Transducers for Neurokinesiological Research and Neural Prostheses

Author: 
Peer reviewed: 
No, item is not peer reviewed.
Date created: 
1998-02
Abstract: 

The objective of this thesis was to develop a family of advanced electrical and mechanical interfaces to record activity of nerves and muscles during natural movements. These interfaces have applications in basic research and may eventually be refined for used in restoring voluntary control of movement in paralyzed persons.

I) A muscle length gauge was designed that is based on piezoelectric crystals attached at the ends of a fluid filled extensible tubing. The in-vivo performance of these gauges was equal to previous length gauge designs. In addition, the ultrasound based design provided for the first time a direct muscle length calibration method.

2) An innovative nerve cuff closing technique was devised that does not reqmre suture closures. The new design uses interdigitated tubes to lock the opening and fix the lumen of a nerve cuff. The cuffs were tested in long-term mammalian implants and their performance matched or surpassed previous closure designs. The nerve cuff was further redesigned to include a more compliant cuff wall and wire electrodes.

3) Floating microelectrodes previously used for central nervous system recordings were adapted for chronic use in the peripheral nervous system. These electrodes proved disappointing in terms of signal quality and longevity. The reasons for failure are thought to be of both electrical and mechanical origin.

4) An innovative silicon micromachined peripheral single unit electrode was designed and tested. In the in-vivo tests, a limited number of recording sites successfully established short-term neural interfaces. However, the quality of the electrode performance, in terms of signal amplitude and ability to discriminate single unit potentials, was insufficient.

5) Using a finite difference model, a numerical simulation of static and dynamic electrical interactions between peripheral axons and microelectrode interfaces was derived. The model consisted of resistive and capacitive elements arranged in a 3-dimensional conductive universe (two spatial dimensions and time). Models of intrafascicular fine wire or silicon based electrodes were used to record simulated propagating action potentials. It was confirmed that electrode movement affected the recorded signal amplitude and that a dielectric layer on a silicon electrode accentuated the recorded potential field. A conducting back plane facing away from axon sources did not have a significant effect on the electrode recording properties.

In conclusion, several novel implantable transducers were developed for use in neurokinesiological research. A numerical simulation of the axonal potentials recorded by intrafascicular electrodes helped interpret various shortcomings found in the in-vivo electrode performance. Although not attempted in the present thesis some of the developed technologies may have potential of transferring to clinical neural prostheses applications.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Joaquin Andres Hoffer
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) Ph.D.

A model of health: Using business analytics to identify older Canadian adults with heart disease

Author: 
Date created: 
2018-12-14
Abstract: 

Nearly 90% of older Canadians have at least one chronic disease; 65% have two or more. The aims of my thesis were to apply business analytics techniques to predict the presence of an exemplar chronic disease, heart disease, among older Canadians, and to calculate the corresponding expected healthcare costs. I used neural networks to develop logistic regression models of heart disease using demographic, lifestyle, and health information for 15,599 older adults from the Canadian Longitudinal Study on Aging. The Economic Burden of Illness in Canada provided healthcare cost data. The best model identified 65.8% of heart disease cases from 40% of participants with the highest predicted probabilities of heart disease, accounting for $2.7 million more expected annual healthcare costs than a randomly sampled 40%. Among all older Canadians, this difference would be $1.1 billion. These methods could assist healthcare decision makers to optimize the delivery of chronic disease prevention interventions.

Document type: 
Thesis
File(s): 
Supervisor(s): 
Dawn Mackey
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.