Philip N Ainslie

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada

Are you Philip N Ainslie?

Claim your profile

Publications (194)668.45 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Experimental physiology 06/2015; DOI:10.1113/EP085143 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    AJP Regulatory Integrative and Comparative Physiology 03/2015; 308(11):ajpregu.00425.2014. DOI:10.1152/ajpregu.00425.2014 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Impaired myocardial systolic contraction and diastolic relaxation have been suggested as possible mechanisms contributing to the decreased stroke volume (SV) observed at high altitude (HA). To determine whether intrinsic myocardial performance is a limiting factor in the generation of SV at HA, we assessed left ventricular (LV) systolic and diastolic mechanics and volumes in 10 healthy participants (aged 32 ± 7; mean ± SD) at rest and during exercise at sea level (SL; 344 m) and following 10 days at 5050 m. In contrast to SL, LV end-diastolic volume was ~19% lower at rest (p=0.004) and did not increase during exercise despite a greater untwisting velocity. Furthermore, resting SV was lower at HA (~17%; 60±10 vs. 70±8 ml) despite higher LV twist (43%), apical rotation (115%) and circumferential strain (17%). With exercise at HA, the increase in SV was limited (12 ml vs. 22 ml at SL), and LV apical rotation failed to augment. For the first time, we have demonstrated that EDV does not increase upon exercise at high altitude despite enhanced in vivo diastolic relaxation. The increase in LV mechanics at rest may represent a mechanism by which SV is defended in the presence of a reduced EDV. However, likely due to the higher LV mechanics at rest, no further increase was observed up to 50% peak power. Consequently, whilst hypoxia does not suppress systolic function per se, the capacity to increase SV through greater deformation during submaximal exercise at HA is restricted. Copyright © 2014, Journal of Applied Physiology.
    Journal of Applied Physiology 03/2015; DOI:10.1152/japplphysiol.00995.2014 · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We examined the impact of progressive hypotension with and without hypocapnia on regional extracranial cerebral blood flow and intra-cranial velocities. Participants underwent progressive lower-body negative pressure until pre-syncope to inflict hypotension. End-tidal carbon dioxide was clamped at baseline levels (isocapnic trial) or uncontrolled (poikilocapnic trial). Middle and posterior cerebral artery blood velocities (transcranial Doppler), heart rate, blood pressure and end-tidal carbon dioxide were obtained continuously. Measurements of internal carotid artery and vertebral artery blood flow were also obtained. Overall, blood pressure was reduced by ~20% from baseline in both trials (P<0.001). In the isocapnic trial, end-tidal carbon dioxide was successfully clamped at baseline with hypotension, whereas in the poikilocapnic trial it was reduced by 11.1 mm Hg (P<0.001) with hypotension. The decline in the internal carotid artery blood-flow with hypotension was comparable between trials (-139 ± 82 ml; ~30%; P<0.0001); however, the decline in the vertebral artery blood flow was -28 ± 22 ml/min (~21%) greater in the poikilocapnic trial compared with the isocapnic trial (P=0.002). Regardless of trial, the blood flow reductions in internal carotid artery (-26 ± 14%) and vertebral artery (-27 ± 14%) were greater than the decline in middle cerebral artery (-21 ± 15%) and posterior middle cerebral artery velocities (-19 ± 10%), respectively (P≤0.01). Significant reductions in the diameter of both the ICA (~5%) and VA (~7%) contributed to the decline in cerebral perfusion with systemic hypotension, independent of hypocapnia. In summary, our findings indicate that blood flow in the VA, unlike the ICA, is sensitive to changes hypotension and hypocapnia. We show for the first time that the decline in global CBF with hypotension is influenced by arterial constriction in the ICA and VA. Additionally, our findings suggest TCD measures of blood flow velocity may modestly underestimate changes in CBF during hypotension with and without hypocapnia, particularly in the posterior circulation.
    Clinical Science 02/2015; DOI:10.1042/CS20140751 · 5.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of partial acclimatization to high altitude (HA; 5,050 m) on cerebral metabolism and cerebrovascular function have not been characterized. We hypothesized (1) increased cerebrovascular reactivity (CVR) at HA; and (2) that CO2 would affect cerebral metabolism more than hypoxia. PaO2 and PaCO2 were manipulated at sea level (SL) to simulate HA exposure, and at HA, SL blood gases were simulated; CVR was assessed at both altitudes. Arterial-jugular venous differences were measured to calculate cerebral metabolic rates and cerebral blood flow (CBF). We observed that (1) partial acclimatization yields a steeper CO2-H(+) relation in both arterial and jugular venous blood; yet (2) CVR did not change, despite (3) mean arterial pressure (MAP)-CO2 reactivity being doubled at HA, thus indicating effective cerebral autoregulation. (4) At SL hypoxia increased CBF, and restoration of oxygen at HA reduced CBF, but neither had any effect on cerebral metabolism. Acclimatization resets the cerebrovasculature to chronic hypocapnia.Journal of Cerebral Blood Flow & Metabolism advance online publication, 18 February 2015; doi:10.1038/jcbfm.2015.4.
    Journal of Cerebral Blood Flow & Metabolism 02/2015; 35(5). DOI:10.1038/jcbfm.2015.4 · 5.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Transfer function analysis (TFA) is a frequently used method to assess dynamic cerebral autoregulation (CA) using spontaneous oscillations in blood pressure (BP) and cerebral blood flow velocity (CBFV). However, controversies and variations exist in how research groups utilise TFA, causing high variability in interpretation. The objective of this study was to evaluate between-centre variability in TFA outcome metrics. 15 centres analysed the same 70 BP and CBFV datasets from healthy subjects (n = 50 rest; n = 20 during hypercapnia); 10 additional datasets were computer-generated. Each centre used their in-house TFA methods; however, certain parameters were specified to reduce a priori between-centre variability. Hypercapnia was used to assess discriminatory performance and synthetic data to evaluate effects of parameter settings. Results were analysed using the Mann-Whitney test and logistic regression. A large non-homogeneous variation was found in TFA outcome metrics between the centres. Logistic regression demonstrated that 11 centres were able to distinguish between normal and impaired CA with an AUC>0.85. Further analysis identified TFA settings that are associated with large variation in outcome measures. These results indicate the need for standardisation of TFA settings in order to reduce between-centre variability and to allow accurate comparison between studies. Suggestions on optimal signal processing methods are proposed.
    Medical Engineering & Physics 01/2015; in press:2014. · 1.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sport-related concussion has been referred to as a functional rather than a structural injury with neurometabolic and microstructural alterations reported in several studies. Accordingly, conventional neuroimaging techniques, such as computed tomography (CT) and structural magnetic resonance imaging (MRI), have limited value beyond ruling out structural injury such as a contusion or hemorrhage. This chapter presents a review of three neuroimaging techniques that offer insight into the connectivity and neurometabolic consequences of concussion. A number of studies have now been published using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI)/diffusion-weighted imaging, and transcranial Doppler ultrasound (TCD) with varying findings. The results of these studies will be presented, together with current and possible future application of these techniques within the field of sport-related concussion.
    01/2015: pages 1; Oxford University Press.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The hypoxic ventilatory response (HVR) at sea level (SL) is moderately predictive of the change in pulmonary artery systolic pressure (PASP) to acute normobaric hypoxia. However, because of progressive changes in the chemoreflex control of breathing and acid-base balance at high altitude (HA), HVR at SL may not predict PASP at HA. We hypothesized that resting peripheral oxyhemoglobin saturation (SpO2) at HA would correlate better than HVR at SL to PASP at HA. Methods: In 20 participants at SL, we measured normobaric, isocapnic HVR (L/min·-%SpO2-1) and resting PASP using echocardiography. Both resting SpO2 and PASP measures were repeated on day 2 (n=10), days 4-8 (n=12), and 2-3 weeks (n=8) after arrival at 5050m. These data were also collected at 5050m on life-long HA residents (Sherpa; n=21). Results: Compared to SL, SpO2 decreased from 98.6 to 80.5% (P<0.001), while PASP increased from 21.7 to 34.0mmHg (P<0.001) after 2-3 weeks at 5050m. Isocapnic HVR at SL was not related to SpO2 or PASP at any time point at 5050m (all P>0.05). Sherpa had lower PASP (P<0.01) than lowlanders on days 4-8 despite similar SpO2. Upon correction for hematocrit, Sherpa PASP was not different from lowlanders at SL, but lower than lowlanders at all HA time points. At 5050m, whilst SpO2 was not related to PASP in lowlanders at any point (all R2=<0.05; P>0.50), there was a weak relationship in the Sherpa (R2=0.16; P=0.07). Conclusion: We conclude that neither HVR at SL nor resting SpO2 at HA correlates with elevations in PASP at HA.
    Chest 12/2014; DOI:10.1378/chest.14-1992 · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Traumatic brain injury influences regulation of cerebral blood flow in animal models and in human studies. We reviewed the use of transcranial Doppler ultrasound (US) to monitor cerebrovascular reactivity following sport-related concussion. A narrative and systematic review of articles published in the English language, from December 1982 to October 2013. Articles were retrieved via numerous databases using relevant key terms. Observational, cohort, correlational, cross-sectional and longitudinal studies were included. Three publications met the criteria for inclusion; these provided data from 42 athletes and 33 controls. All three studies reported reductions in cerebrovascular reactivity via transcranial Doppler US. These initial results support the use of cerebrovascular reactivity as a research tool for identifying altered neurophysiology and monitoring recovery in adult athletes. Larger cross-sectional, prospective and longitudinal studies are required to understand the sensitivity and prognostic value of cerebrovascular reactivity in sport-related concussion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    British Journal of Sports Medicine 12/2014; DOI:10.1136/bjsports-2014-093901 · 5.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cerebrovascular reactivity impacts CO2/[H+] washout at the central chemoreceptors and hence has marked influence on the control of ventilation. To date, the integration of cerebral blood flow (CBF) and ventilation has been investigated exclusively with measures of anterior CBF, which has a differential reactivity from the vertebrobasilar system, which perfuses the brainstem. We hypothesized that: 1) posterior versus anterior CBF would have a stronger relationship to central chemoreflex magnitude during hypercapnia, and 2) that higher posterior reactivity would lead to a greater hypoxic ventilatory decline (HVD). End-tidal forcing was used to induce steady-state hyperoxic (300 mmHg PETO2) hypercapnia (+3, +6 and +9 mmHg PETCO2) and isocapnic hypoxia (45 mmHg PETO2) before and following pharmacological blunting (Indomethacin; INDO; 1.45±0.17 mg/kg) of resting CBF and reactivity. In 22 young healthy volunteers, ventilation, intra-cranial arterial blood velocities and extra-cranial blood flows were measured during these challenges. INDO-induced blunting of cerebrovascular flow responsiveness (CVR) to CO2 was unrelated to variability in ventilatory sensitivity during hyperoxic hypercapnia. Further results in a sub-group of volunteers (n = 9) revealed that elevations of PETCO2 via end-tidal forcing reduce arterial-jugular venous gradients, attenuating the effect of CBF on chemoreflex responses. During isocapnic hypoxia, vertebral artery CVR was related to the magnitude of HVD (R2 = 0.27; P<0.04; n = 16), suggesting that CO2/[H+] washout from central chemoreceptors modulates hypoxic ventilatory dynamics. No relationships were apparent with anterior CVR. As higher posterior, but not anterior, CVR was linked to HVD, our study highlights the importance of measuring flow in posterior vessels to investigate CBF and ventilatory integration.This article is protected by copyright. All rights reserved
    The Journal of Physiology 12/2014; 593(5). DOI:10.1113/jphysiol.2014.284521 · 4.54 Impact Factor
  • Source
    Patrice Brassard, Philip N Ainslie, Niels H Secher
    [Show abstract] [Hide abstract]
    ABSTRACT: Monitoring cerebral blood flow (CBF) and oxygenation has implications for both clinical practice and research interests; e.g., to provide insight into functional neurovascular coupling, to better understand orthostatic hypotension, and to evaluate the influence of vasopressors on cerebral oxygenation during anes-thesia and/or surgery. These topics, and others, are addressed in this e-book by presenting original research, reviews, and opin-ion papers covering new, exciting but also controversial issues related to cerebral oxygenation in health and disease as evaluated by near-infrared spectroscopy (NIRS). There is interest in the impact of vasopressors on the NIRS-determined frontal lobe oxygenation (S c O 2). For example, a reduction in S c O 2 is reported with use of phenylephrine and noradrenaline at rest in healthy subjects, during anesthesia in non-cardiac and cardiac patients and during cardiopulmonary bypass in diabetics. However, possible extracranial contami-nation of the NIRS signal, especially with the utilization of vasopressors, challenges these conclusions. Keeping this limi-tation in mind, Foss et al. (2014) explored the influence of phenylephrine and ephedrine, on S c O 2 during cesarean sec-tion with spinal anesthesia. Both vasopressors were effective at maintaining mean arterial pressure (MAP). Still, phenyle-phrine was the agent associated with a reduction in S c O 2 . In addition, Kitchen et al. (2014) studied the effect of calcium chloride compared to α-and β-adrenergic receptor agonists (ephedrine, phenylephrine, adrenaline, or noradrenaline) follow-ing anesthesia-induced hypotension in patients scheduled for major abdominal surgery. This case series suggested that S c O 2 was preserved in patients who received calcium chloride, as well as β-adrenergic receptor agonists, but slightly reduced (2%) in those who received α-adrenergic drugs. Also, ventilation, O 2 supplementation and body position have the potential to affect NIRS-derived S c O 2 during surgery. Larsen et al. (2014) explored whether induction of anesthesia in the reclining, compared to sitting beach-chair position, secures cere-brovascular hemodynamics, including S c O 2 . S c O 2 was found to be higher, combined with more stable hemodynamics, character-ized by a reduced utilization of ephedrine, following induction of anesthesia in the reclining beach-chair vs. the sitting posi-tion. In their retrospective analyses of patients undergoing liver transplantation, Sørensen et al. (2014) report that S c O 2 changes during surgery were closely related to those in end-tidal carbon dioxide tension. In order to ensure stability in S c O 2 during the different phases of a liver transplantation, a varying ventilatory strategy may be needed to reduce the incidence of postoper-ative complications. Rokamp et al. (2014a) examined whether O 2 supplementation could maintain S c O 2 and skeletal muscle oxygenation in vascular surgical patients. These authors con-clude that O 2 supplementation indeed elevates S c O 2 and skele-tal muscle oxygenation in these patients during surgery but does not seem to sufficiently prevent a critical reduction in S c O 2 . Nielsen (2014) reviewed the impact of different surgeries on S c O 2 . His report indicates that the impact of non-cardiac surgery on S c O 2 is highly variable and in some types of surgery, cerebral desaturation may be related to postoperative cognitive dysfunction. Arterial pressure influences CBF. However, the role of arterial pressure variability on clinical outcome is not clear. Bronzwaer et al. (2014) explored the relationship between arterial pres-sure variations, stroke volume index and regional cerebral per-fusion during transient central blood volume depletion and repletion in healthy volunteers and found that middle cere-bral artery flow velocity (MCA Vmean) is related linearly to arterial pressure variability in subjects under these conditions. In their review, Rickards and Tzeng (2014) tried to recon-cile two apparently discrepant views regarding variability in arterial pressure and CBF (negative vs. positive impact on clinical outcome), and suggest that the time scale of hemo-dynamic variability, that is short time variability vs. longer term fluctuations, may be the key to merge these divergent views. To better understand the integrative components of cere-brovascular control, and thus oxygenation, during hyperthermia, Bain et al. (2014) discuss the mechanisms related to CBF and oxygenation changes during moderate to severe levels of hyper-thermia. On the opposite spectrum, a reduction in cerebral temperature (hypothermia) may be important, for example to prevent cerebral ischemia during anesthesia or to improve neu-rological outcome and survival after cardiac arrest. Nybo et al. (2014) explored the impact of different means of brain cooling on cerebral temperature balance and oxygenation, namely intranasal cooling, percutaneous cooling of the carotid arteries and nasal ventilation. Other physiological challenges influence CBF and oxygena-tion. Rokamp et al. (2014b) explored whether cholinergic vasodi-latation is of importance for the elevation in regional CBF, measured by arterial spin labeling and blood O 2 level depen-dent functional magnetic resonance imaging during a handgrip
    Frontiers in Physiology 11/2014; 5. DOI:10.3389/fphys.2014.00458 · 3.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The roles of involuntary breathing movements (IBMs) and cerebral oxygen delivery in the tolerance to extreme hypoxemia displayed by elite breath-hold divers are unknown. Cerebral blood flow (CBF), arterial blood gases (ABGs), and cardiorespiratory metrics were measured during maximum dry apneas in elite breath-hold divers (n=17). To isolate the effects of apnea and IBM from the concurrent changes on ABG, end-tidal forcing ('clamp') was then used to replicate an identical temporal pattern of decreasing arterial PO2 (PaO2) and increasing arterial PCO2 (PaCO2) while breathing. End-apnea PaO2 ranged from 23 to 37 mm Hg (30±7 mm Hg). Elevation in mean arterial pressure was greater during apnea than during clamp reaching +54±24% versus 34±26%, respectively; however, CBF increased similarly between apnea and clamp (93.6±28% and 83.4±38%, respectively). This latter observation indicates that during the overall apnea period IBM per se do not augment CBF and that the brain remains sufficiently protected against hypertension. Termination of apnea was not determined by reduced cerebral oxygen delivery; despite 40% to 50% reductions in arterial oxygen content, oxygen delivery was maintained by commensurately increased CBF.Journal of Cerebral Blood Flow & Metabolism advance online publication, 5 November 2014; doi:10.1038/jcbfm.2014.170.
    Journal of Cerebral Blood Flow & Metabolism 11/2014; 35(1). DOI:10.1038/jcbfm.2014.170 · 5.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cerebral blood flow responses to transient blood pressure challenges are frequently attributed to cerebral autoregulation (CA), yet accumulating evidence indicates vascular properties like compliance are also influential. We hypothesized that middle cerebral blood velocity (MCAv) dynamics during or following a transient blood pressure perturbation can be accurately explained by the windkessel mechanism. Eighteen volunteers underwent blood pressure manipulations, including bilateral thigh-cuff deflation and sit-to-stand maneuvers under normocapnic and hypercapnic (5% CO2) conditions. Pressure-flow recordings were analyzed using a windkessel analysis approach that partitions the frequency-dependent resistance and compliance contributions to MCAv dynamics. The windkessel was typically able to explain more than 50% of the MCAv variance, as indicated by R2 values for both the flow recovery and postrecovery phase. The most consistent predictors of MCAv dynamics under the control condition were the windkessel capacitive gain and high-frequency resistive gain. However, there were significant interindividual variations in the composition of windkessel predictors. Hypercapnia consistently reduced the capacitive gain and enhanced the low-frequency (0.04–0.20 Hz) resistive gain for both thigh-cuff deflation and sit-to-stand trials. These findings indicate that 1) MCAv dynamics during acute transient hypotension challenges are dominated by cerebrovascular windkessel properties independent of CA; 2) there is significant heterogeneity in windkessel properties between individuals; and 3) hemodynamic effects of hypercapnia during transient blood pressure challenges primarily reflect changes in windkessel properties rather than pure CA impairment.
    Journal of Applied Physiology 11/2014; 117(9):1037-1048. DOI:10.1152/japplphysiol.00366.2014 · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased with exposure to acute hypoxia and has been associated with pulmonary artery systolic pressure (PASP). We aimed to determine the direct relationship between blood flow through IPAVA and PASP in 10 participants with no detectable intracardiac shunt by comparing: (1) isocapnic hypoxia (control); (2) isocapnic hypoxia with oral administration of acetazolamide (AZ; 250 mg, three times-a-day for 48 h) to prevent increases in PASP, and (3) isocapnic hypoxia with AZ and 8.4% NaHCO3 infusion (AZ+HCO3−) to control for AZ-induced acidosis. Isocapnic hypoxia (20 min) was maintained by end-tidal forcing, blood flow through IPAVA was determined by agitated saline contrast echocardiography and PASP was estimated by Doppler ultrasound. Arterial blood samples were collected at rest before each isocapnic-hypoxia condition to determine pH, [HCO3−], and PaCO2. AZ decreased pH (-0.08 ± 0.01), [HCO3−] (-7.1 ± 0.7 mmol/l), and PaCO2 (-4.5 ± 1.4 mmHg; p<0.01), while intravenous NaHCO3 restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (p<0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (p<0.001) following AZ administration while intravenous NaHCO3 partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (p<0.01) and was unrelated to PASP, cardiac output and pulmonary vascular resistance for all conditions. In conclusion, isocapnic hypoxia induces blood flow through IPAVA independent of changes in PASP and the influence of AZ on the PASP response to isocapnic hypoxia is dependent upon the H+ concentration or PaCO2.This article is protected by copyright. All rights reserved
    The Journal of Physiology 11/2014; 593(3). DOI:10.1113/jphysiol.2014.282962 · 4.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heart transplant recipients are at an increased risk for cerebral hemorrhage and ischemic stroke; yet, the exact mechanism for this derangement remains unclear. We hypothesized that alterations in cerebrovascular regulation is principally involved. To test this hypothesis, we studied cerebral pressure-flow dynamics in 8 clinically stable male heart transplant recipients (62±8 years of age and 9±7 years post transplant, mean±SD), 9 male age-matched controls (63±8 years), and 10 male donor controls (27±5 years). To increase blood pressure variability and improve assessment of the pressure-flow dynamics, subjects performed squat-stand maneuvers at 0.05 and 0.10 Hz. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal carbon dioxide were continuously measured during 5 minutes of seated rest and throughout the squat-stand maneuvers. Cardiac baroreceptor sensitivity gain and cerebral pressure-flow responses were assessed with linear transfer function analysis. Heart transplant recipients had reductions in R-R interval power and baroreceptor sensitivity low frequency gain (P<0.01) compared with both control groups; however, these changes were unrelated to transfer function metrics. Thus, in contrast to our hypothesis, the increased risk of cerebrovascular complication after heart transplantation does not seem to be related to alterations in cerebral pressure-flow dynamics. Future research is, therefore, warranted.
    Hypertension 10/2014; 64(6). DOI:10.1161/HYPERTENSIONAHA.114.04236 · 7.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of vasovagal syncope is more common in the morning. Previous researchers have reported negligible diurnal variation in the physiological responses associated with initial orthostatic hypotension (IOH). Nevertheless, physical activity and sleep prior to morning and afternoon test times have not been controlled and may influence the findings. We designed a semi-constant routine protocol to examine diurnal variation in cardiorespiratory and cerebrovascular responses to active standing.
    Arbeitsphysiologie 10/2014; 115(2). DOI:10.1007/s00421-014-3010-y · 2.30 Impact Factor
  • Mike Stembridge, Philip N. Ainslie, Rob Shave
    [Show abstract] [Hide abstract]
    ABSTRACT: Both short-term and life-long high altitude (HA) exposure challenge the cardiovascular system to meet the metabolic demand for oxygen (O2) in a hypoxic environment. As the demand for O2 delivery increases during exercise, the circulatory component of oxygen transport is placed under additional stress. Acute adaptation and chronic remodelling of cardiac structure and function may occur to facilitate O2 delivery in lowlanders during sojourn to high altitude and in permanent highland residents. However our understanding of cardiac structural and functional adaption in Sherpa remains confined to a higher maximal heart rate, lower pulmonary vascular resistance and no differences in resting cardiac output. Ventricular form and function are intrinsically linked through the left ventricular (LV) mechanics that facilitate efficient ejection, minimise myofibre stress during contraction and aid diastolic recoil. Recent examination of LV mechanics has allowed detailed insight into fundamental cardiac adaptation in HA Sherpa. In this symposium report, we review recent advances in our understanding of LV function in both lowlanders and Sherpa at rest, and discuss the potential consequences for exercise capacity. Collectively, data indicate chronic structural ventricular adaptation, with adult Sherpa having smaller absolute and relative LV size. Consistent with structural remodelling, cardiac mechanics also differ in Sherpa when compared to lowlanders at HA. These differences are characterised by a reduction in resting systolic deformation and slower diastolic untwisting, a surrogate of relaxation. These changes may reflect a functional cardiac adaptation that affords Sherpa the same mechanical reserve seen in lowlanders at sea level, which is absent when they ascend to HA.This article is protected by copyright. All rights reserved
    Experimental physiology 10/2014; DOI:10.1113/expphysiol.2014.082503 · 2.87 Impact Factor
  • Philip N Ainslie, Ryan L Hoiland
    Journal of Applied Physiology 09/2014; 117(10). DOI:10.1152/japplphysiol.00854.2014 · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We examined two novel hypotheses: 1) That orthostatic tolerance (OT) would be prolonged when hyperventilatory-induced hypocapnia (and hence cerebral hypoperfusion) was prevented; and 2) that pharmacological reductions in cerebral blood flow (CBF) at baseline would lower the “CBF reserve”, and ultimately reduce OT. In Study 1 (n = 24; aged 25±4 y) participants underwent progressive lower-body negative pressure (LBNP) until pre-syncope; end-tidal carbon dioxide (PETCO2) was clamped at baseline levels (isocapnic trial) or uncontrolled. In Study 2 (n = 10; aged 25±4 y), CBF was pharmacologically reduced by administration of indomethacin (INDO; 1.2 mg/kg) or unaltered (placebo) followed by LBNP to pre-syncope. Beat-by-beat measurements of middle cerebral artery blood flow velocity (MCAv; transcranial Doppler), heart rate (ECG), blood pressure (BP; Finometer) and end-tidal gases were obtained continuously. In a subset of subjects’ arterial-to-jugular venous differences were obtained to examine the independent impact of hypocapnia or cerebral hypoperfusion (following INDO) on cerebral oxygen delivery and extraction. Study 1: During the isocapnic trial, PETCO2 was successfully clamped at baseline levels at pre-syncope (38.3±2.7 vs. 38.5±2.5 mm Hg respectively; P = 0.50). In the uncontrolled trial, PETCO2 at pre-syncope was reduced by 10.9±3.9 mm Hg (P≤0.001). Compared to the isocapnic trial, the decline in mean MCAv was 15±4 cm∙s−1 (35%; P≤0.001) greater in the uncontrolled trial, yet the time to pre-syncope was comparable between trials (544±130 v 572±180 s; P = 0.30). Study 2: Compared to placebo, INDO reduced resting MCAv by 19±4 cm∙s−1 (31%; P≤0.001), but time to pre-syncope remained similar between trials (placebo: 1123±138 vs. INDO: 1175±212 s; P = 0.53). The brain extracted more oxygen in face of hypocapnia (34% to 53%) or cerebral hypoperfusion (34% to 57%) to compensate for reductions in delivery. In summary, cerebral hypoperfusion either at rest or induced by hypocapnia at pre-syncope does not impact OT, likely due to a compensatory increase in oxygen extraction.This article is protected by copyright. All rights reserved
    The Journal of Physiology 09/2014; 592(23). DOI:10.1113/jphysiol.2014.280586 · 4.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Cerebral autoregulation (CA) is a theoretical construct characterized by the relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF). We performed a comprehensive literature search to provide an up-to-date review on the static relationship between MAP and CBF. Methods The results are based on 40 studies (49 individual experimental protocols) in healthy subjects between 18 and 65 years. Exclusion criteria were: a ΔMAP <5%, hypoxia/hyperoxia or hypo/hypercapnia, and unstable levels (<2 min stages). The partial pressure of arterial CO2 (PaCO2) was measured in a subset of the included studies (n = 28); therefore, CBF was also adjusted to account for small changes in PaCO2. Results The linear regression coefficient between MAP and CBF (or velocity) of 0.82 ± 0.77%ΔCBF/%ΔMAP during decreases in MAP (n = 23 experiments) was significantly different than the relationship of 0.21 ± 0.47%ΔCBF/%ΔMAP during increases (n = 26 experiments; p < 0.001). After correction for increases/decreases in PaCO2, the slopes were not significantly different: 0.64 ± 1.16%ΔCBF/%ΔMAP (n = 16) and 0.39 ± 0.30%ΔCBF/%ΔMAP (n = 12) for increased vs. decreased MAP changes, respectively (p = 0.60). Conclusion The autoregulatory ability of the cerebral circulation appears to be more active in buffering increases in MAP as compared to reductions in MAP. However, the statistical finding of hysteresis is lost following an attempt to correct for PaCO2.
    Medical Engineering & Physics 09/2014; 36(11). DOI:10.1016/j.medengphy.2014.08.001 · 1.84 Impact Factor

Publication Stats

3k Citations
668.45 Total Impact Points


  • 2010–2015
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 2009–2015
    • 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
    • University of North Texas HSC at Fort Worth
      • Department of Integrative Physiology
      Fort Worth, TX, United States
  • 2013
    • Laval University
      Quebec City, Quebec, Canada
  • 2012
    • University of Wales
      Cardiff, Wales, United Kingdom
    • Government of British Columbia, Canada
      Vancouver, British Columbia, Canada
  • 2005–2012
    • University of Otago
      • Department of Physiology
      Taieri, Otago Region, New Zealand
  • 2003–2010
    • The University of Calgary
      • • Faculty of Medicine
      • • Faculty of Kinesiology
      Calgary, Alberta, Canada
  • 2002–2007
    • Liverpool John Moores University
      • Research Institute for Sport and Exercise Sciences (RISES)
      Liverpool, England, United Kingdom
    • Maastricht University
      Maestricht, Limburg, Netherlands