Philip N Ainslie

University of British Columbia - Okanagan, Kelowna, British Columbia, Canada

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Publications (216)716.18 Total impact

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    ABSTRACT: The purpose of this study was to examine ventricular structure and function in Sherpa adolescents to determine whether age-specific differences in oxygen saturation and pulmonary artery systolic pressure (PASP) influence cardiac adaptation to chronic hypoxia early in life. Two-dimensional, Doppler and speckle-tracking echocardiography were performed on adolescent (9-16 years) highland Sherpa (HLS; 3840 m; n=26) and compared with age-matched lowland Sherpa (LLS; 1400 m; n=10) and lowland Caucasian controls (LLC; sea level; n=30). The HLS were subdivided into pre- and post-adolescence; SpO2 was also recorded. Only HLS exhibited a smaller relative LV EDV; however, both HLS and LLS demonstrated a lower peak LV untwisting velocity in comparison to LLC (92±26 and 100±45 vs. 130±43 °/s, P<0.05). Although SpO2 was similar between groups, PASP was higher in post- vs. pre-adolescent HLS (30±5 vs. 25±5 mmHg, P<0.05) which negatively correlated with RV strain rate (r=0.50, P<0.01). Much like their adult counterparts, HLS and LLS adolescents exhibit slower LV diastolic relaxation despite residing at different altitudes. These findings suggest fundamental differences exist in the diastolic function of Sherpa that are present at an early age and may be retained after migration to lower altitudes. The higher PASP in post-adolescent Sherpa is in contrast to previous reports of lowland children at HA and unlike lowlanders, was not explained by differences in SpO2; thus, different regulatory mechanisms seem to exist between these two distinct populations.
    No preview · Article · Jan 2016 · AJP Heart and Circulatory Physiology
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    ABSTRACT: Cerebral blood flow (CBF) is temporally related to exercise-induced changes in partial pressure of end-tidal carbon dioxide (PETCO2); hyperoxia is known to enhance this relationship. We examined the hypothesis that preventing PETCO2 from rising (isocapnia) during submaximal exercise with and without hyperoxia (end-tidal PO2, [PETCO2] = 300 mmHg) would attenuate the increases in CBF. Additionally, we aimed to identify the magnitude that breathing, per se, influences the CBF response to normoxic and hyperoxic exercise. In 14 participants, CBF (intra- and extra-cranial CBF) measurements were measured during exercise (20, 40, 60, 80% of maximum workload [Wmax]) and during rest while ventilation (V̇E) was volitionally increased to mimic volumes achieved during exercise (isocapnic hyperpnea). While V̇E was uncontrolled during poikilocapnic exercise, during isocapnic exercise and isocapnic hyperpnea, V̇E was increased to prevent PETCO2 from rising above resting values (~40 mmHg). Although PETCO2 differed by 2±3 mmHg during normoxic poikilocapnic and isocapnic exercise, except for a greater poikilocapnic compared with isocapnic increase in blood velocity in the posterior cerebral artery at 60% Wmax, the between condition increases in intracranial (~12-15%) and extra-cranial (15-20%) CBF were similar at each workload. The poikilocapnic hyperoxic increases in both intra- and extra-cranial CBF (~17-29 %) were greater compared to poikilocapnic normoxia (~8-20%) at intensities >40% WMax (P<0.01). During both normoxic and hyperoxic conditions, isocapnia normalized both the intracranial and extra-cranial CBF differences. Isocapnic hyperpnea did not alter CBF. Our findings demonstrate a differential effect of PETCO2 on CBF during exercise influenced by the prevailing PETCO2.
    No preview · Article · Jan 2016 · Journal of Applied Physiology
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    ABSTRACT: This review highlights the influence of oxygen (O2) availability on cerebral blood flow (CBF). Evidence for reductions in O2 content (CaO2) rather than arterial O2 tension (PaO2) as the chief regulator of cerebral vasodilation, with deoxyhemoglobin as the primary O2 sensor and upstream response effector is discussed. We review in vitro and in vivo data to summarize the molecular mechanisms underpinning CBF responses during changes in CaO2. We surmise that; 1) during hypoxemic hypoxia in healthy humans (e.g., conditions of acute and chronic exposure to normobaric and hypobaric hypoxia), elevations in CBF compensate for reductions in CaO2 and thus maintain cerebral O2 delivery; 2) evidence from studies implementing iso- and hyper-volumic hemodilution, anemia, and polycythemia, indicate that CaO2 has an independent influence on CBF; however, the increase in CBF does not fully compensate for the lower CaO2 during hemodilution, and delivery is reduced; and 3) the mechanisms underpinning CBF regulation during changes in O2 content are multifactorial, involving deoxyhemoglobin-mediated release of nitric oxide metabolites and ATP, deoxyhemoglobin nitrite reductase activity, and the downstream interplay of several vasoactive factors including adenosine and epoxyeicosatrienoic acids. The emerging picture supports the role of deoxyhemoglobin (associated with changes in CaO2) as the primary biological regulator of CBF. The mechanisms for vasodilation therefore appear more robust during hypoxemic hypoxia than during changes in CaO2 via hemodilution. Clinical implications (e.g., disorders associated with anemia and polycythemia) and future study directions are considered.
    No preview · Article · Dec 2015 · AJP Regulatory Integrative and Comparative Physiology
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    Full-text · Dataset · Dec 2015
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    ABSTRACT: Carotid chemoreceptors detect changes in arterial PO2 and PCO2 , eliciting a peripheral chemoreflex (PCR). Steady-state (SS) hypoxia tests using dynamic end-tidal forcing (DEF) have been used to assess the hypoxic ventilatory response (HVR), but may be confounded by concomitant systemic effects. Transient tests of the PCR have also been developed, but are not widely utilized, nor have the cardiovascular and cerebrovascular responses been characterized. We characterized the cardiorespiratory and cerebrovascular responses to transient tests of the PCR and compared the HVR between transient and SS-DEF tests. We hypothesized that the cardiovascular and cerebrovascular responses to the transient tests would be minimal and that the respiratory responses elicited from the transient and SS-DEF tests would be different in magnitude and not well correlated, within-individuals. Participants underwent five consecutive trials of two transient tests (three-breath 100% N2 [TT-N2 ] and a single-breath 13% CO2 , in air) and two 10-min SS-DEF tests (isocapnic [SS-ISO] and poikilocapnic [SS-POI] hypoxia). In response to the transient tests, heart rate, mean arterial pressure, and the middle and posterior cerebral artery blood velocity increased (all P<0.01), but responses were small (all < 10%) and transient. Although the TT-N2 and SS-POI tests elicited similar HVR magnitudes, they were not well-correlated within-individuals (r = 0.064, P = 0.79). The TT-N2 test elicited a smaller HVR than the SS-ISO test, but they were correlated within-individuals (r = 0.57, P = 0.008). Because the transient tests exploit the temporal domain of the peripheral chemoreceptors and have minimal cardiovascular and cerebrovascular confounders, we suggest that they may have broader utility than previously appreciated. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Experimental physiology
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    ABSTRACT: Although high-altitude exposure can lead to neurocognitive impairment, even upon return to sea level, it remains unclear the extent to which brain volume and regional cerebral vascular reactivity (CVR) are altered following high-altitude exposure. The purpose of this study was to simultaneously determine the effect of 3 weeks at 5050 m on: (1) structural brain alterations; and (2) regional CVR after returning to sea level for 1 week. Healthy human volunteers (n = 6) underwent baseline and follow-up structural and functional magnetic resonance imaging (MRI) at rest and during a CVR protocol (end-tidal PCO2 reduced by −10, −5 and increased by +5, +10, and +15 mmHg from baseline). CVR maps (% mmHg−1) were generated using BOLD MRI and brain volumes were estimated. Following return to sea level, whole-brain volume and gray matter volume was reduced by 0.4 ± 0.3% (P < 0.01) and 2.6 ± 1.0% (P < 0.001), respectively; white matter was unchanged. Global gray matter CVR and white matter CVR were unchanged following return to sea level, but CVR was selectively increased (P < 0.05) in the brainstem (+30 ± 12%), hippocampus (+12 ± 3%), and thalamus (+10 ± 3%). These changes were the result of improvement and/or reversal of negative CVR to positive CVR in these regions. Three weeks of high-altitude exposure is reflected in loss of gray matter volume and improvements in negative CVR.
    Full-text · Article · Dec 2015
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    ABSTRACT: Carotid chemoreceptors detect changes in arterial PO2 and PCO2, eliciting a peripheral chemoreflex (PCR). Steady-state (SS) hypoxia tests using dynamic end-tidal forcing (DEF) have been used to assess the hypoxic ventilatory response (HVR), but may be confounded by concomitant systemic effects. Transient tests of the PCR have also been developed, but are not widely utilized, nor have the cardiovascular and cerebrovascular responses been characterized. We characterized the cardiorespiratory and cerebrovascular responses to transient tests of the PCR and compared the HVR between transient and SS-DEF tests. We hypothesized that the cardiovascular and cerebrovascular responses to the transient tests would be minimal and that the respiratory responses elicited from the transient and SS-DEF tests would be different in magnitude and not well correlated, within-individuals. Participants underwent five consecutive trials of two transient tests (three-breath 100% N2 [TT-N2] and a single-breath 13% CO2, in air) and two 10-min SS-DEF tests (isocapnic [SS-ISO] and poikilocapnic [SS-POI] hypoxia). In response to the transient tests, heart rate, mean arterial pressure, and the middle and posterior cerebral artery blood velocity increased (all P<0.01), but responses were small (all <10%) and transient. Although the TT-N2 and SS-POI tests elicited similar HVR magnitudes, they were not well-correlated within-individuals (r=0.064, P=0.79). The TT-N2 test elicited a smaller HVR than the SS-ISO test, but they were correlated within-individuals (r=0.57, P=0.008). Because the transient tests exploit the temporal domain of the peripheral chemoreceptors and have minimal cardiovascular and cerebrovascular confounders, we suggest that they may have broader utility than previously appreciated.
    No preview · Article · Nov 2015 · Experimental Physiology
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    ABSTRACT: Neurovascular coupling reflects the close temporal and regional linkage between neural activity and cerebral blood flow. Although providing mechanistic insight, our understanding of neurovascular coupling is largely limited to non-physiological ex vivo preparations and non-human models using sedatives/anesthetics with confounding cerebrovascular implications. Herein, with particular focus on humans, we review the present mechanistic understanding of neurovascular coupling and highlight current approaches to assess these responses and the application in health and disease. Moreover, we present new guidelines for standardizing the assessment of neurovascular coupling in humans. To improve the reliability of measurement and related interpretation, the utility of new automated software for neurovascular coupling is demonstrated, which provides the capacity for coalescing repetitive trials and time intervals into single contours and extracting numerous metrics (e.g., conductance and pulsatility, critical closing pressure, etc.) according to patterns of interest (e.g., peak/minimum response, time of response, etc.). This versatile software also permits the normalization of neurovascular coupling metrics to dynamic changes in arterial blood gases, potentially influencing the hyperemic response. It is hoped that these guidelines, combined with the newly developed and openly available software, will help to propel the understanding of neurovascular coupling in humans and also lead to improved clinical management of this critical physiological function.
    Preview · Article · Nov 2015 · Journal of Cerebral Blood Flow & Metabolism
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    ABSTRACT: The cerebral pressure-flow relationship can be quantified as a high-pass filter, where slow oscillations are buffered (<0.20 Hz) and faster oscillations are passed through relatively unimpeded. During moderate intensity exercise previous studies have reported paradoxical transfer function analysis (TFA) findings (altered phase or intact gain). This study aimed to determine if these previous findings accurately represent this relationship. Both younger (20-30 years; n=10) and older (62-72 years; n=9) adults were examined. To enhance the signal-to-noise ratio, large oscillations in blood pressure (via oscillatory lower body negative pressure - OLBNP) that were induced during steady-state moderate intensity supine exercise (~45-50% of heart rate reserve). Beat-to-beat blood pressure, cerebral blood velocity, and end-tidal PCO2 were monitored. Very low (VLF: 0.02-0.07 Hz) and low frequency (LF: 0.07-0.20 Hz) range spontaneous data was quantified. Driven OLBNP point-estimates were sampled at 0.05 and 0.10 Hz. The OLBNP maneuvers augmented coherence to >0.97 at 0.05 Hz and >0.98 at 0.10 Hz in both age-groups. The OLBNP protocol conclusively revealed the cerebrovascular system functions as a high-pass filter during exercise throughout aging. It was also discovered that the older adults had elevations [+71%] in normalized gain (+0.46 ± 0.36 %/%: 0.05 Hz) and reductions [-34%] in phase (-0.24 ± 0.22 radians: 0.10 Hz). There were also age-related phase differences between resting and exercise conditions. It is speculated that these age-related changes in the TFA metrics are mediated by alterations in vasoactive factors, sympathetic tone or the mechanical buffering of the compliance vessels.
    No preview · Article · Nov 2015 · Journal of Applied Physiology
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    ABSTRACT: One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies which combine (a) the use of equipment, (b) problem solving, (c) visual representations, and (d) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The “Duffin” hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to carbon dioxide (CO2). We aim to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2, and illustrate the integration of the respiratory and cerebrovascular systems. Methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, coefficient of determination (R2), and the differences between plotting absolute vs. normalized data. Utilizing the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate and medical students with an advanced understanding of integrative nature of human physiology.
    No preview · Article · Nov 2015 · AJP Advances in Physiology Education
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    ABSTRACT: Transient reduction in vascular function following systemic large muscle group exercise has previously been reported in humans. The mechanisms responsible are currently unknown. We hypothesised that sympathetic nervous system activation, induced by cycle ergometer exercise, would contribute to post-exercise reductions in flow-mediated dilation (FMD). Ten healthy male subjects (28 ± 5years) undertook two 30 minute sessions of cycle exercise at 75% HRmax. Prior to exercise, individuals ingested either a placebo or an α1 -adrenoreceptor blocker (Prazosin; 0.05mg.kg(-1) ). Central hemodynamics, brachial artery shear rate (SR) and blood flow profiles were assessed throughout each exercise bout and in response to brachial artery FMD, measured prior to-, immediately after, and 60-minutes post-exercise. Cycle exercise increased both mean and antegrade SR (P < 0.001) with retrograde SR also elevated under both conditions (P < 0.001). Pre-exercise FMD was similar on both occasions, and significantly reduced (27%) immediately following exercise in the placebo condition (t-test, P = 0.03). In contrast, FMD increased (37%) immediately following exercise in the Prazosin condition (t-test, P = 0.004, interaction effect P = 0.01). Post-exercise FMD remained different between conditions after correction for baseline diameters preceding cuff deflation and also post-deflation shear rate. No differences in FMD or other variables were evident 60-minutes following recovery. Our results indicate that sympathetic vasoconstriction competes with endothelium-dependent dilator activity to determine post-exercise arterial function. These findings have implications for understanding the chronic impacts of interventions, such as exercise training, which affect both sympathetic activity and arterial shear stress. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · The Journal of Physiology
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    ABSTRACT: Excessive sedentary behaviour has serious clinical and public health implications; however, the physiological changes that accompany prolonged sitting in the child are not completely understood. Herein, we examined the acute effect a prolonged period of sitting has upon superficial femoral artery function in 7- to 10-year-old girls and the impact of interrupting prolonged sitting with exercise breaks. Superficial femoral artery endothelium-dependent flow-mediated dilatation, total shear rate, anterograde and retrograde shear rates and oscillatory shear index were assessed before and after two experimental conditions: a 3 h uninterrupted period of sitting (SIT) and a 3 h period of sitting interrupted each hour with 10 min of moderate-intensity exercise (EX). A mixed-model analysis of variance was used to compare between-condition and within-condition main effects, controlling for the within-subject nature of the experiment by including random effects for participant. Superficial femoral artery endothelium-dependent flow-mediated dilatation decreased significantly from pre- to post-SIT (mean difference 2.2% flow-mediated dilatation; 95% confidence interval = 0.60-2.94%, P < 0.001). This relative decline of 33% was abolished in the EX intervention. Shear rates were not significantly different within conditions. Our data demonstrate the effectiveness of short but regular exercise breaks in offsetting the detrimental effects of uninterrupted sitting in young girls.
    No preview · Article · Sep 2015 · Experimental physiology

  • No preview · Article · Sep 2015 · European Respiratory Journal
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    Mike Stembridge · Philip N Ainslie · Rob Shave
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    ABSTRACT: High-altitude exposure challenges the cardiovascular system to maintain oxygen delivery to the mitochondria under conditions of hypoxic stress. Following acclimatisation (3-5 days), stroke volume (SV) falls to below sea-level values but heart rate remains elevated, such that cardiac output is maintained compared to sea level. The decrease in SV has been a topic of research for over 40 years, but the underlying mechanisms are incompletely understood. Impaired systolic contractile function secondary to reduced coronary arterial oxygen tension has been investigated as a potential cause for the decrease in SV. However, despite in vitro evidence of impaired cardiac contractile force in severe hypoxia, the majority of studies to date have reported enhanced in vivo ventricular systolic function at rest and during exercise in humans up to and above 5000 m. However, the elevated function observed at rest has recently been suggested to reduce the functional reserve available during exercise. While in vivo systolic function appears enhanced at high altitude, a decrease in left ventricular end-diastolic volume (EDV) and altered filling patterns of both ventricles has been observed. The reduction in ventricular filling will undoubtedly affect SV, and four potential mechanisms have been proposed to explain the reduction in left ventricular filling. In this article, both historical and recent reports of systolic function at high altitude will be reviewed, and evidence supporting and refuting each of the four mechanisms underpinning reduced left ventricular filling will be discussed.
    Full-text · Article · Sep 2015
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    ABSTRACT: The purpose of this study was to determine the impact of peripheral chemoreflex inhibition with low-dose dopamine on maximal apnea time, and the related hemodynamic and cerebrovascular responses in elite apnea divers. In a randomized order, participants performed a maximal apnea while receiving either I.V. 2µg・kg(-1)・min(-1) dopamine or volume matched saline (placebo). The chemoreflex and hemodynamic response to dopamine was also assessed during hypoxia (arterial O2 tension, [PaO2]~35mmHg) and mild hypercapnia (arterial CO2 tension [PaCO2]~46mmHg) that mimicked the latter parts of apnea. Outcome measures included apnea duration, arterial blood gases (radial), heart rate (HR, ECG), mean arterial pressure (MAP, intra-arterial), middle (MCAv) and posterior (PCAv) cerebral artery blood velocity (transcranial ultrasound), internal carotid (ICA) and vertebral (VA) artery blood flow (ultrasound), and the chemoreflex responses. Although dopamine depressed the ventilatory response by 27±41% (vs. placebo; p=0.01), the maximal apnea duration was increased by only 5±8% (p=0.02). The PaCO2 and PaO2 at apnea breakpoint were similar (p>0.05). Compared to placebo, dopamine increased HR and decreased MAP during both apnea and chemoreflex test (p all<0.05). At rest, dopamine compared to placebo dilated the ICA (3.0±4.1%, p=0.05) and VA (6.6±5.0%, p<0.01). During apnea and chemoreflex test, conductance of the cerebral vessels (ICA, VA, MCAv, PCAv) was increased with dopamine; however, flow (ICA and VA) was similar. At least in elite apnea divers, the small increase in apnea time and similar PaO2 at breakpoint (~31mmHg) suggest the apnea breakpoint is more related to PaO2, rather than peripheral chemoreflex drive to breathe. Copyright © 2015, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    No preview · Article · Aug 2015 · AJP Regulatory Integrative and Comparative Physiology
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    ABSTRACT: We examined the between-day reproducibility of active (squat-stand maneuvers) and passive (oscillatory lower body negative pressure [OLBNP] maneuvers) driven oscillations in blood pressure. These relationships were examined in both younger (n=10; 25 ± 3 years) and older (n=9; 66 ± 4 years) adults. Each testing protocol incorporated rest (5-minutes), followed by driven maneuvers at 0.05 (5-minuntes) and 0.10 Hz (5-minuntes) to increase blood pressure variability and improve assessment of the pressure-flow dynamics using linear transfer function analysis. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal PCO2 were monitored. The pressure-flow relationship was quantified in the very low (0.02-0.07 Hz) and low (0.07-0.20 Hz) frequencies (spontaneous data) and at 0.05 and 0.10 Hz (driven maneuvers point estimates). Although there were no between age-differences, very few spontaneous and OLBNP transfer function metrics met the criteria for acceptable reproducibility as reflected in between-day within-subject coefficient of variation (CoV) of <20%. Combined CoV data: LF coherence (15.1 ± 12.2%), LF gain (15.1 ± 12.2%) and LF normalized gain (18.5 ± 10.9%). OLBNP data: 0.05 Hz coherence (12.1 ± 15.%), 0.10 Hz coherence (4.7 ± 7.8%). In contrast, the squat-stand maneuvers revealed that all metrics (coherence: 0.6 ± 0.5%, 0.3 ± 0.5%; gain: 17.4 ± 12.3%, 12.7 ± 11.0%; normalized gain: 16.7 ± 10.9%, 15.7 ± 11.0%; and phase: 11.6 ± 10.2%, 17.3 ± 10.8%) at 0.05 and 0.10 Hz, respectively, were considered biologically acceptable for reproducibility. These findings have important implications for the reliable assessment and interpretation of cerebral-pressure flow dynamics in humans. Copyright © 2015, Journal of Applied Physiology.
    No preview · Article · Jul 2015 · Journal of Applied Physiology
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    Kate N Thomas · Nia C S Lewis · Brigid G Hill · Philip N Ainslie
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    ABSTRACT: Duplex ultrasound is evolving technology that allows the assessment of volumetric blood flow in the carotid and vertebral arteries during a range of interventions along the spectrum of health and chronic disease. Duplex ultrasound can provide high-resolution diameter and velocity information in real-time, and is non-invasive with minimal risks or contra-indications. However, this ultrasound approach is a specialized technique requiring intensive training and stringent control of multiple complex settings; results are highly operator-dependent, and analysis approaches are inconsistent. Importantly, therefore, methodological differences can invalidate comparisons between different imaging modalities and studies; such methodological errors therefore have potential to discredit study findings completely. The task of this review is to provide the first comprehensive, user-friendly technical guideline for the application of duplex ultrasound in measuring extracranial blood flow in human research. An update on recent developments in the use of edge-detection software for offline analysis is highlighted, and suggestions for future directions in this field are provided. These recommendations are presented in an attempt to standardize measurements across research groups and hence ultimately will improve the accuracy and reproducibility of measuring extracranial blood flow both within-subjects and between groups. Copyright © 2015, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    Full-text · Article · Jul 2015 · AJP Regulatory Integrative and Comparative Physiology
  • Anthony R Bain · Lars Nybo · Philip N Ainslie
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    ABSTRACT: This review provides an in-depth update on the impact of heat stress on cerebrovascular functioning. The regulation of cerebral temperature, blood flow, and metabolism are discussed. We further provide an overview of vascular permeability, the neurocognitive changes, and the key clinical implications and pathologies known to confound cerebral functioning during hyperthermia. A reduction in cerebral blood flow (CBF), derived primarily from a respiratory-induced alkalosis, underscores the cerebrovascular changes to hyperthermia. Arterial pressures may also become compromised because of reduced peripheral resistance secondary to skin vasodilatation. Therefore, when hyperthermia is combined with conditions that increase cardiovascular strain, for example, orthostasis or dehydration, the inability to preserve cerebral perfusion pressure further reduces CBF. A reduced cerebral perfusion pressure is in turn the primary mechanism for impaired tolerance to orthostatic challenges. Any reduction in CBF attenuates the brain's convective heat loss, while the hyperthermic-induced increase in metabolic rate increases the cerebral heat gain. This paradoxical uncoupling of CBF to metabolism increases brain temperature, and potentiates a condition whereby cerebral oxygenation may be compromised. With levels of experimentally viable passive hyperthermia (up to 39.5-40.0 °C core temperature), the associated reduction in CBF (∼ 30%) and increase in cerebral metabolic demand (∼ 10%) is likely compensated by increases in cerebral oxygen extraction. However, severe increases in whole-body and brain temperature may increase blood-brain barrier permeability, potentially leading to cerebral vasogenic edema. The cerebrovascular challenges associated with hyperthermia are of paramount importance for populations with compromised thermoregulatory control--for example, spinal cord injury, elderly, and those with preexisting cardiovascular diseases.
    No preview · Article · Jul 2015 · Comprehensive Physiology
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    ABSTRACT: Following exercise a reduction in mean arterial pressure (MAP) is often experienced and is referred to as post-exercise hypotension (PEH). Whilst syncope is more likely following exercise, it is unknown whether orthostatic tolerance is impacted by any exercise-intensity mediated effect on PEH. We examined the effect of exercise intensity on time to presyncope, induced via combined head-up tilt and lower body negative pressure following one-hour cycling at 30 and 70% of heart rate range (HRR). Healthy participants (n = 8, mean±SD: 28 ± 5 y) completed orthostatic testing to presyncope before and following exercise. Beat-to-beat middle cerebral artery blood flow velocity (MCAv), MAP and cerebral oxygenation (NIRS) were recorded continuously throughout orthostatic testing. During exercise, heart rates were 95 ± 6 and 147 ± 5 b∙min(-1) for 30% and 70% HRR, respectively, with average power outputs 103 ± 22 and 221 ± 45 watts, respectively. Time to presyncope occurred 32% faster following the 70% HRR trial (952 ± 484 s vs. 1418 ± 435 s, p = 0.004). Both before and following exercise, presyncope occurred at the same reduction in MCAv (grouped mean -30 ± 11 cm∙s(-1) ), MAP (-18 ± 13 mm Hg), total oxygenation index (-6 ± 2%) and partial pressure of end tidal CO2 (PET CO2 , -16 ± 8 mm Hg, all P > 0.1). At presyncope following exercise the MCAv response was related more to the change in PET CO2 from the baseline preceding orthostatic testing (R(2) = 0.50, P = 0.01) than to the hypotension (R(2) = 0.12, P = 0.17). Presyncope both before and following exercise occurred as a result of the same physiological perturbations, albeit greatly accelerated following more intense exercise. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jun 2015 · Experimental physiology
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    ABSTRACT: We sought to characterize and quantify the performance of a portable dynamic end-tidal forcing (DEF) system in controlling the partial pressure of arterial CO2 (PaCO2) and O2 (PaO2) at low- (LA; 344m) and high-altitude (HA; 5050m) during an isooxic CO2 test, and an isocapnic O2 test, commonly used to measure ventilatory and vascular reactivity in humans (n=9). The isooxic CO2 tests involved step changes in the partial pressure of end-tidal carbon dioxide (PETCO2) of -10, -5, 0, +5 and +10 mmHg from baseline. The isocapnic O2 test consisted of a 10-min hypoxic step (PETO2=47mmHg) from baseline at LA, and a 5-min euoxic step (PETO2=100mmHg) from baseline at HA. At both altitudes, PETO2 and PETCO2 were controlled within narrow limits (<1mmHg from target) during each protocol. During the isooxic CO2 test at LA, PETCO2 consistently overestimated PaCO2 (P<0.01) at both baseline (2.1±0.5mmHg) and hypercapnia (+5mmHg: 2.1±0.7mmHg; +10mmHg: 1.9±0.5mmHg). This Pa-PETCO2 gradient was approximately two-fold greater at HA (P<0.05). At baseline at both altitudes, PETO2 overestimated PaO2 by a similar extent (LA: 6.9±2.1mmHg; HA: 4.5±0.9mmHg; both P<0.001). This overestimation persisted during isocapnic hypoxia at LA (6.9±0.6mmHg), and during isocapnic euoxia at HA (3.8±1.2mmHg). Step-wise multiple regression analysis, on the basis of the collected data, revealed that it may be possible to predict an individual's arterial blood gases during DEF. Future research is needed to validate these prediction algorithms, and determining the implications of end-tidal-to-arterial gradients in the assessment of ventilatory and/or vascular reactivity. Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    Full-text · Article · Mar 2015 · AJP Regulatory Integrative and Comparative Physiology

Publication Stats

4k Citations
716.18 Total Impact Points

Institutions

  • 2009-2016
    • University of British Columbia - Okanagan
      • • School of Health and Exercise Sciences
      • • Faculty of Health and Social Development
      Kelowna, British Columbia, Canada
    • University of Lincoln
      Lincoln, England, United Kingdom
  • 2015
    • Cardiff Metropolitan University
      Cardiff, Wales, United Kingdom
  • 2010-2015
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 2005-2015
    • University of Otago
      • Department of Physiology
      Taieri, Otago, New Zealand
  • 2013
    • Laval University
      Quebec City, Quebec, Canada
  • 2012
    • University of Wales
      Cardiff, Wales, United Kingdom
    • Government of British Columbia, Canada
      Vancouver, British Columbia, Canada
  • 2003-2010
    • The University of Calgary
      • Faculty of Medicine
      Calgary, Alberta, Canada
  • 2002
    • Liverpool John Moores University
      • Research Institute for Sport and Exercise Sciences (RISES)
      Liverpool, England, United Kingdom