Biomedical Physiology and Kinesiology, Department of

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Comparison of Autonomic Control of Blood Pressure During Standing and Artificial Gravity Induced via Short-Arm Human Centrifuge

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2018-06-25
Abstract: 

Autonomic control of blood pressure is essential toward maintenance of cerebral perfusion during standing, failure of which could lead to fainting. Long-term exposure to microgravity deteriorates autonomic control of blood pressure. Consequently, astronauts experience orthostatic intolerance on their return to gravitational environment. Ground-based studies suggest sporadic training in artificial hypergravity can mitigate spaceflight deconditioning. In this regard, short-arm human centrifuge (SAHC), capable of creating artificial hypergravity of different g-loads, provides an auspicious training tool. Here, we compare autonomic control of blood pressure during centrifugation creating 1-g and 2-g at feet with standing in natural gravity. Continuous blood pressure was acquired simultaneously from 13 healthy participants during supine baseline, standing, supine recovery, centrifugation of 1-g, and 2-g, from which heart rate (RR) and systolic blood pressure (SBP) were derived. The autonomic blood pressure regulation was assessed via spectral analysis of RR and SBP, spontaneous baroreflex sensitivity, and non-linear heart rate and blood pressure causality (RR↔SBP). While majority of these blood pressure regulatory indices were significantly different (p < 0.05) during standing and 2-g centrifugation compared to baseline, no change (p > 0.05) was observed in the same indices during 2-g centrifugation compared to standing. The findings of the study highlight the capability of artificial gravity (2-g at feet) created via SAHC toward evoking blood pressure regulatory controls analogous to standing, therefore, a potential utility toward mitigating deleterious effects of microgravity on cardiovascular performance and minimizing post-flight orthostatic intolerance in astronauts.

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The Critical Power Model as a Potential Tool for Anti-doping

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2018-06-06
Abstract: 

Existing doping detection strategies rely on direct and indirect biochemical measurement methods focused on detecting banned substances, their metabolites, or biomarkers related to their use. However, the goal of doping is to improve performance, and yet evidence from performance data is not considered by these strategies. The emergence of portable sensors for measuring exercise intensities and of player tracking technologies may enable the widespread collection of performance data. How these data should be used for doping detection is an open question. Herein, we review the basis by which performance models could be used for doping detection, followed by critically reviewing the potential of the critical power (CP) model as a prototypical performance model that could be used in this regard. Performance models are mathematical representations of performance data specific to the athlete. Some models feature parameters with physiological interpretations, changes to which may provide clues regarding the specific doping method. The CP model is a simple model of the power-duration curve and features two physiologically interpretable parameters, CP and W′. We argue that the CP model could be useful for doping detection mainly based on the predictable sensitivities of its parameters to ergogenic aids and other performance-enhancing interventions. However, our argument is counterbalanced by the existence of important limitations and unresolved questions that need to be addressed before the model is used for doping detection. We conclude by providing a simple worked example showing how it could be used and propose recommendations for its implementation.

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Evaluation of Forearm Vascular Resistance during Orthostatic Stress: Velocity Is Proportional to Flow and Size Doesn’t Matter

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-11-15
Abstract: 

Background

The upright posture imposes a significant challenge to blood pressure regulation that is compensated through baroreflex-mediated increases in heart rate and vascular resistance. Orthostatic cardiac responses are easily inferred from heart rate, but vascular resistance responses are harder to elucidate. One approach is to determine vascular resistance as arterial pressure/blood flow, where blood flow is inferred from ultrasound-based measurements of brachial blood velocity. This relies on the as yet unvalidated assumption that brachial artery diameter does not change during orthostatic stress, and so velocity is proportional to flow. It is also unknown whether the orthostatic vascular resistance response is related to initial blood vessel diameter.

Methods

We determined beat-to-beat heart rate (ECG), blood pressure (Portapres) and vascular resistance (Doppler ultrasound) during a combined orthostatic stress test (head-upright tilting and lower body negative pressure) continued until presyncope. Participants were 16 men (aged 38.4±2.3 years) who lived permanently at high altitude (4450m).

Results

The supine brachial diameter ranged from 2.9–5.6mm. Brachial diameter did not change during orthostatic stress (supine: 4.19±0.2mm; tilt: 4.20±0.2mm; -20mmHg lower body negative pressure: 4.19±0.2mm, p = 0.811). There was no significant correlation between supine brachial artery diameter and the maximum vascular resistance response (r = 0.323; p = 0.29). Forearm vascular resistance responses evaluated using brachial arterial flow and velocity were strongly correlated (r = 0.989, p<0.00001) and demonstrated high equivalency with minimal bias (-6.34±24.4%).

Discussion

During severe orthostatic stress the diameter of the brachial artery remains constant, supporting use of brachial velocity for accurate continuous non-invasive orthostatic vascular resistance responses. The magnitude of the orthostatic forearm vascular resistance response was unrelated to the baseline brachial arterial diameter, suggesting that upstream vessel size does not matter in the ability to mount a vasoconstrictor response to orthostasis.

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Association between Sedentary Behaviour and Physical, Cognitive, and Psychosocial Status among Older Adults in Assisted Living

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2017-08-24
Abstract: 

Objective. Identification of the factors that influence sedentary behaviour in older adults is important for the design of appropriate intervention strategies. In this study, we determined the prevalence of sedentary behaviour and its association with physical, cognitive, and psychosocial status among older adults residing in Assisted Living (AL). Methods. Participants (, mean age = 86.7) from AL sites in British Columbia wore waist-mounted activity monitors for 7 consecutive days, after being assessed with the Timed Up and Go (TUG), Montreal Cognitive Assessment (MoCA), Short Geriatric Depression Scale (GDS), and Modified Fall Efficacy Scale (MFES). Results. On average, participants spent 87% of their waking hours in sedentary behaviour, which accumulated in 52 bouts per day with each bout lasting an average of 13 minutes. Increased sedentary behaviour associated significantly with scores on the TUG (, ) and MFES (, ), but not with the MoCA or GDS. Sedentary behaviour also associated with male gender, use of mobility aid, and multiple regression with increased age. Conclusion. We found that sedentary behaviour among older adults in AL associated with TUG scores and falls-related self-efficacy, which are modifiable targets for interventions to decrease sedentary behaviour in this population.

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Depolarization Of The Conductance-Voltage Relationship In The Nav1.5 Mutant, E1784K, Is Due To Altered Fast Inactivation

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2017-09-12
Abstract: 

E1784K is the most common mixed long QT syndrome/Brugada syndrome mutant in the cardiac voltage-gated sodium channel NaV1.5. E1784K shifts the midpoint of the channel conductance-voltage relationship to more depolarized membrane potentials and accelerates the rate of channel fast inactivation. The depolarizing shift in the midpoint of the conductance curve in E1784K is exacerbated by low extracellular pH. We tested whether the E1784K mutant shifts the channel conductance curve to more depolarized membrane potentials by affecting the channel voltage-sensors. We measured ionic currents and gating currents at pH 7.4 and pH 6.0 in Xenopus laevis oocytes. Contrary to our expectation, the movement of gating charges is shifted to more hyperpolarized membrane potentials by E1784K. Voltage-clamp fluorimetry experiments show that this gating charge shift is due to the movement of the DIVS4 voltage-sensor being shifted to more hyperpolarized membrane potentials. Using a model and experiments on fast inactivation-deficient channels, we show that changes to the rate and voltage-dependence of fast inactivation are sufficient to shift the conductance curve in E1784K. Our results localize the effects of E1784K to DIVS4, and provide novel insight into the role of the DIV-VSD in regulating the voltage-dependencies of activation and fast inactivation.

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Article
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Mobility-Related Gaze Training in Individuals With Glaucoma: A Proof-of-Concept Study

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-10-09
Abstract: 

Purpose: Older adults with glaucoma show inappropriate gaze strategies during routine mobility tasks. Furthermore, glaucoma is a risk factor for falling and colliding with objects when walking. However, effective interventions to rectify these strategies and prevent these adverse events are scarce. We designed a gaze training program with the goal of providing proof-of-concept that we could modify mobility-related gaze behavior in this population.

Methods: A total of 13 individuals with moderate glaucoma participated in this study. We taught participants general and task-specific gaze strategies over two 1-hour sessions. To determine the efficacy of this gaze training program, participants performed walking tasks that required accurate foot placement onto targets and circumventing obstacles before and after training. We used a mobile eye tracker to quantify gaze and a motion-capture system to quantify body movement.

Results: After training, we found changes in the timing between gaze shifts away from targets relative to stepping on them (P < 0.05). In the obstacle negotiation task, we found a greater range of gaze shifts early in walking trials and changes in the timing between gaze shifts away from obstacles after training (P < 0.05), each suggesting better route planning. A posttraining reduction in foot-placement error and obstacle collisions accompanied these changes (P < 0.05).

Conclusions: Our results demonstrated that it is possible to modify mobility-related gaze behavior and mobility performance in older adults with glaucoma.

Translational Relevance: This study provides proof-of-concept for a gaze training program for glaucoma. A larger, randomized controlled trial is warranted.

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Article
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Dynamic Wheelchair Seating Positions Impact Cardiovascular Function after Spinal Cord Injury

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2107-06-30
Abstract: 

Background

Innovative wheelchairs allow individuals to change position easily for comfort and social situations. While these wheelchairs are beneficial in multiple ways, the effects of position changes on blood pressure might exacerbate hypotension and cerebral hypoperfusion, particularly in those with spinal cord injury (SCI) who can have injury to autonomic nerves that regulate cardiovascular control. Conversely, cardiovascular benefits may be obtained with lowered seating. Here we investigate the effect of moderate changes in wheelchair position on orthostatic cardiovascular and cerebrovascular reflex control.

Methods

Nineteen individuals with SCI and ten neurologically-intact controls were tested in supine and seated positions (neutral, lowered, and elevated) in the Elevation™ wheelchair. Participants with SCI were stratified into two groups by the severity of injury to cardiovascular autonomic pathways. Beat-to-beat blood pressure, heart rate and middle cerebral artery blood flow velocity (MCAv) were recorded non-invasively.

Results

Supine blood pressure and MCAv were reduced in individuals with lesions to autonomic pathways, and declined further with standard seating compared to those with preserved autonomic control. Movement to the elevated position triggered pronounced blood pressure and MCAv falls in those with autonomic lesions, with minimum values significantly reduced compared to the seated and lowered positions. The cumulative duration spent below supine blood pressure was greatest in this group. Lowered seating bolstered blood pressure in those with lesions to autonomic pathways.

Conclusions

Integrity of the autonomic nervous system is an important variable that affects cardiovascular responses to orthostatic stress and should be considered when individuals with SCI or autonomic dysfunction are selecting wheelchairs.

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Pubertal Hormonal Changes and the Autonomic Nervous System: Potential Role in Pediatric Orthostatic Intolerance

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-11-12
Abstract: 

Puberty is initiated by hormonal changes in the adolescent body that trigger physical and behavioral changes to reach adult maturation. As these changes occur, some adolescents experience concerning pubertal symptoms that are associated with dysfunction of the autonomic nervous system (ANS). Vasovagal syncope (VVS) and Postural Orthostatic Tachycardia Syndrome (POTS) are common disorders of the ANS associated with puberty that are related to orthostatic intolerance and share similar symptoms. Compared to young males, young females have decreased orthostatic tolerance and a higher incidence of VVS and POTS. As puberty is linked to changes in specific sex and non-sex hormones, and hormonal therapy sometimes improves orthostatic symptoms in female VVS patients, it is possible that pubertal hormones play a role in the increased susceptibility of young females to autonomic dysfunction. The purpose of this paper is to review the key hormonal changes associated with female puberty, their effects on the ANS, and their potential role in predisposing some adolescent females to cardiovascular autonomic dysfunctions such as VVS and POTS. Increases in pubertal hormones such as estrogen, thyroid hormones, growth hormone, insulin, and insulin-like growth factor-1 promote vasodilatation and decrease blood volume. This may be exacerbated by higher levels of progesterone, which suppresses catecholamine secretion and sympathetic outflow. Abnormal heart rate increases in POTS patients may be exacerbated by pubertal increases in leptin, insulin, and thyroid hormones acting to increase sympathetic nervous system activity and/or catecholamine levels. Given the coincidental timing of female pubertal hormone surges and adolescent onset of VVS and POTS in young women, coupled with the known roles of these hormones in modulating cardiovascular homeostasis, it is likely that female pubertal hormones play a role in predisposing females to VVS and POTS during puberty. Further research is necessary to confirm the effects of female pubertal hormones on autonomic function, and their role in pubertal autonomic disorders such as VVS and POTS, in order to inform the treatment and management of these debilitating disorders.

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Investigating the Utility of Adult Zebrafish Ex Vivo Whole Hearts to Pharmacologically Screen hERG Channel Activator Compounds

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2019-10-30
Abstract: 

There is significant interest in the potential utility of small molecule activator compounds to mitigate cardiac arrhythmia caused by loss-of-function of hERG1a voltage-gated potassium channels. Zebrafish (Danio rerio) have been proposed as a cost effective, high throughput drug-screening model to identify compounds that cause hERG1a dysfunction. However, there are no reports on the effects of hERG1a activator compounds in zebrafish, and consequently on the utility of the model to screen for potential gain-of-function therapeutics. Here, we examined the effects of hERG1a blocker, and type 1 and type 2 activator, compounds on isolated zkcnh6a (zERG3) channels in the Xenopus laevis oocyte heterologous expression system, as well as action potentials recorded from ex vivo adult zebrafish whole hearts using optical mapping. Our functional data from isolated zkcnh6a channels show that these channels respond to hERG1a channel blockers (dofetilide and terfenadine), and type 1 (RPR260243) and type 2 (NS1643, PD-118057) hERG1a activator compounds, in a similar manner to hKCNH2a channels, with minor differences largely accounted for by subtly different biophysical properties in the two channels. In ex vivo zebrafish whole hearts, two of the three hERG1a activators examined caused abbreviation of the APD, while hERG1a blockers caused APD prolongation. These data represent, to our knowledge, the first pharmacological characterization of isolated zkcnh6a channels and the first assessment of hERG enhancing therapeutics in zebrafish. Our findings suggest that the zebrafish ex vivo whole heart model serves as a valuable tool in the screening of hKCNH2a blocker and activator compounds.

Document type: 
Article

The Super-Seniors Study: Phenotypic Characterization of a Healthy 85+ Population

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2018-05-24
Abstract: 

Background

To understand why some people live to advanced age in good health and others do not, it is important to study not only disease, but also long-term good health. The Super-Seniors Study aims to identify factors associated with healthy aging.

Methods

480 healthy oldest-old ‘Super-Seniors’ aged 85 to 105 years and never diagnosed with cancer, cardiovascular disease, diabetes, dementia, or major pulmonary disease, were compared to 545 mid-life controls aged 41–54, who represent a group that is unselected for survival from late-life diseases. Health and lifestyle information, personal and family medical history, and blood samples were collected from all participants. Super-Seniors also underwent four geriatric tests.

Results

Super-Seniors showed high cognitive (Mini-Mental State Exam mean = 28.3) and functional capacity (Instrumental Activities of Daily Living Scale mean = 21.4), as well as high physical function (Timed Up and Go mean = 12.3 seconds) and low levels of depression (Geriatric Depression Scale mean = 1.5). Super-Seniors were less likely to be current smokers than controls, but the frequency of drinking alcohol was the same in both groups. Super-Seniors were more likely to have 4 or more offspring; controls were more likely to have no children. Female Super-Seniors had a mean age of last fertility 1.9 years older than controls, and were 2.3 times more likely to have had a child at ≥ 40 years. The parents of Super-Seniors had mean ages of deaths of 79.3 years for mothers, and 74.5 years for fathers, each exceeding the life expectancy for their era by a decade.

Conclusions

Super-Seniors are cognitively and physically high functioning individuals who have evaded major age-related chronic diseases into old age, representing the approximately top 1% for healthspan. The familiality of long lifespan of the parents of Super-Seniors supports the hypothesis that heritable factors contribute to this desirable phenotype.

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