ORCID Profile
0000-0002-4413-5615
Current Organisation
The University of Auckland
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Publisher: American Physiological Society
Date: 09-2020
DOI: 10.1152/JAPPLPHYSIOL.00160.2020
Abstract: We found dietary nitrate supplementation reduced blood pressure and brain blood flow fluctuations and improved the relationship between blood pressure and brain blood flow in transient ischemic attack patients. Meanwhile, dietary nitrate had no effects on the brain blood vessels’ response to CO 2 . We attribute the improved brain blood flow stability to the improved myogenic control of blood pressure with dietary nitrate. Our findings indicate that dietary nitrate could be an effective strategy for stabilizing blood pressure and brain blood flow following transient ischemic attack.
Publisher: Wiley
Date: 31-12-2020
DOI: 10.1113/EP088938
Publisher: Springer Science and Business Media LLC
Date: 12-10-2011
DOI: 10.1007/S00421-010-1679-0
Abstract: Indomethacin (INDO) has the potential to be a useful tool to explore the influence of cerebral blood flow and its responses to CO(2) on ventilatory control. However, the effect of INDO on the cerebrovascular and ventilatory response to hypoxia remains unclear therefore, we examined the effect of INDO on ventilatory and cerebrovascular sensitivity to hypoxia and hypercapnia. We measured end-tidal gases, ventilation (V(e)), and middle cerebral artery velocity (MCAv) before and 90 min following INDO (100 mg) in 12 healthy participants at rest and during hyperoxic hypercapnia and isocapnic hypoxia. Following INDO, resting VE and end-tidal gases were unaltered (P > 0.05), whilst MCAv was lowered by 25 ± 19% (P < 0.001). INDO ingestion reduced MCAv-CO(2) reactivity by 46 ± 29% (2.9 ± 0.9 vs. 1.7 ± 0.9 cm s(-1) mmHg(-1) P < 0.001) and enhanced the VE-CO(2) sensitivity by 0.5 ± 0.5 L min(-1) mmHg(-1) (1.9 ± 1.5 vs. 2.3 ± 1.6 L min(-1) mmHg(-1) P 0.05). These findings indicate that INDO does not alter cerebrovascular and ventilatory responsiveness to hypoxia, indicating a preserved peripheral chemoreflex in response to this pharmacological agent.
Publisher: Mary Ann Liebert Inc
Date: 06-2016
Abstract: Fan, Jui-Lin, and Bengt Kayser. Fatigue and exhaustion in hypoxia: the role of cerebral oxygenation. High Alt Med Biol. 17:72-84, 2016.-It is well established that ascent to high altitude is detrimental to one's aerobic capacity and exercise performance. However, despite more than a century of research on the effects of hypoxia on exercise performance, the underlying mechanisms remain incompletely understood. While the cessation of exercise, or the reduction of its intensity, at exhaustion, implies reduced motor recruitment by the central nervous system, the mechanisms leading up to this muscular derecruitment remain elusive. During exercise in normoxia and moderate hypoxia (∼1500-2500 m), peripheral fatigue and activation of muscle afferents probably play a major role in limiting exercise performance. Meanwhile, studies suggested that cerebral tissue deoxygenation may play a pivotal role in impairing aerobic capacity during exercise in more severe hypoxic conditions (∼4500-6000 m). However, recent studies using end-tidal CO2 cl ing, to improve cerebral tissue oxygenation during exercise in hypoxia, failed to demonstrate an improvement in exercise performance. In light of these recent findings, which seem to contradict the hypothetical role of cerebral tissue deoxygenation as a performance limiting factor at high altitude, this short review aims to provide a critical reappraisal of the extant literature and ends exploring some potential avenues for further research in this field.
Publisher: Wiley
Date: 28-01-2022
DOI: 10.1113/JP282707
Publisher: SAGE Publications
Date: 14-07-2021
DOI: 10.1177/0271678X211032029
Abstract: Optimizing cerebral perfusion is key to rescuing salvageable ischemic brain tissue. Despite being an important determinant of cerebral perfusion, there are no effective guidelines for blood pressure (BP) management in acute stroke. The control of cerebral blood flow (CBF) involves a myriad of complex pathways which are largely unaccounted for in stroke management. Due to its unique anatomy and physiology, the cerebrovascular circulation is often treated as a stand-alone system rather than an integral component of the cardiovascular system. In order to optimize the strategies for BP management in acute ischemic stroke, a critical reappraisal of the mechanisms involved in CBF control is needed. In this review, we highlight the important role of collateral circulation and re-examine the pathophysiology of CBF control, namely the determinants of cerebral perfusion pressure gradient and resistance, in the context of stroke. Finally, we summarize the state of our knowledge regarding cardiovascular and cerebrovascular interaction and explore some potential avenues for future research in ischemic stroke.
Publisher: Wiley
Date: 21-02-2012
Publisher: Mary Ann Liebert Inc
Date: 03-2014
Abstract: We describe a case of experimentally induced pre-syncope in a healthy young man when exposed to increased inspired CO2 in a background of hypoxia. Acute severe hypoxia (FIO2=0.10) was tolerated, but adding CO2 to the inspirate caused pre-syncope symptoms accompanied by hypotension and large reductions in both mean and diastolic middle cerebral artery velocity, while systolic flow velocity was maintained. The mismatch of cerebral perfusion pressure and vascular tone caused unique retrograde cerebral blood flow at the end of systole and a reduction in cerebral tissue oxygenation. We speculate that this occurrence of pre-syncope was due to hypoxia-induced inhibition of brain regions responsible for compensatory sympathetic activity to relative hypercapnia.
Publisher: SAGE Publications
Date: 26-07-2021
DOI: 10.1177/0271678X211033732
Abstract: Restoring perfusion to ischemic tissue is the primary goal of acute ischemic stroke care, yet only a small portion of patients receive reperfusion treatment. Since blood pressure (BP) is an important determinant of cerebral perfusion, effective BP management could facilitate reperfusion. But how BP should be managed in very early phase of ischemic stroke remains a contentious issue, due to the lack of clear evidence. Given the complex relationship between BP and cerebral blood flow (CBF)—termed cerebral autoregulation (CA)—bedside monitoring of cerebral perfusion and oxygenation could help guide BP management, thereby improve stroke patient outcome. The aim of INFOMATAS is to ‘ identify novel therapeutic targets for treatment and management in acute ischemic stroke’. In this review, we identify novel physiological parameters which could be used to guide BP management in acute stroke, and explore methodologies for monitoring them at the bedside. We outline the challenges in translating these potential prognostic markers into clinical use.
Publisher: Wiley
Date: 28-01-2011
Publisher: Wiley
Date: 12-05-2022
DOI: 10.1113/JP282327
Abstract: The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex activation. Ten women (29 ± 6 years, 22.8 ± 2.4 kg/m 2 : mean ± SD) and 10 men (30 ± 7 years, 24.8 ± 3.2 kg/m 2 ) undertook randomized 5 min breathing trials of: room air (eucapnia), isocapnic hypoxia (10% oxygen (O 2 ) peripheral chemoreflex activation), hypercapnic hyperoxia (7% carbon dioxide (CO 2 ), 50% O 2 central chemoreflex activation) and hypercapnic hypoxia (7% CO 2 , 10% O 2 central and peripheral chemoreflex activation). Control trials of isocapnic hyperoxia (peripheral chemoreflex inhibition) and hypocapnic hyperoxia (central and peripheral chemoreflex inhibition) were also included. Muscle sympathetic nerve activity (MSNA microneurography), mean arterial pressure (MAP finger photoplethysmography) and minute ventilation ( E pneumotachometer) were measured. Total MSNA ( P = 1.000 and P = 0.616), MAP ( P = 0.265) and E ( P = 0.587 and P = 0.472) were not different in men and women during eucapnia and during isocapnic hypoxia. Women exhibited attenuated increases in E during hypercapnic hyperoxia (27.3 ± 6.3 vs . 39.5 ± 7.5 l/min, P 0.0001) and hypercapnic hypoxia (40.9 ± 9.1 vs . 53.8 ± 13.3 l/min, P 0.0001) compared with men. However, total MSNA responses were augmented in women (hypercapnic hyperoxia 378 ± 215 vs . 258 ± 107%, P = 0.017 hypercapnic hypoxia 607 ± 290 vs . 362 ± 268%, P 0.0001). No sex differences in total MSNA, MAP or E were observed during isocapnic hyperoxia and hypocapnic hyperoxia. Our results indicate that young women have augmented sympathetic responses to central chemoreflex activation, which explains the augmented MSNA response to combined central and peripheral chemoreflex activation. Sex differences in the control of breathing have been well studied, but whether there are differences in the sympathetic neurocirculatory responses to chemoreflex activation between healthy women and men is incompletely understood. We observed that, compared with young men, young women displayed augmented increases in muscle sympathetic nerve activity during both hypercapnic hyperoxia (central chemoreflex activation) and hypercapnic hypoxia (central and peripheral chemoreflex activation) but had attenuated increases in minute ventilation. In contrast, no sex differences were found in either muscle sympathetic nerve activity or minute ventilation responses to isocapnic hypoxia (peripheral chemoreceptor stimulation). Young women have blunted ventilator, but augmented sympathetic responses, to central (hypercapnic hyperoxia) and combined central and peripheral chemoreflex activation (hypercapnic hypoxia), compared with young men. The possible causative association between the reduced ventilation and heightened sympathetic responses in young women awaits validation.
Publisher: Frontiers Media SA
Date: 16-07-2018
Publisher: Wiley
Date: 14-04-2023
DOI: 10.1113/JP284249
Abstract: Increased peripheral chemoreflex sensitivity is a pathogenic feature of human hypertension (HTN), while both central and peripheral chemoreflex sensitivities are reportedly augmented in animal models of HTN. Herein, we tested the hypothesis that both central and combined central and peripheral chemoreflex sensitivities are augmented in HTN. Fifteen HTN participants (68 ± 5 years mean ± SD) and 13 normotensives (NT 65 ± 6 years) performed two modified rebreathing protocols in which the partial pressure of end‐tidal carbon dioxide () progressively increased while the partial pressure of end‐tidal oxygen was cl ed at either 150 mmHg (isoxic hyperoxia central chemoreflex activation) or 50 mmHg (isoxic hypoxia combined central and peripheral chemoreflex activation). Ventilation ( pneumotachometer) and muscle sympathetic nerve activity (MSNA microneurography) were recorded, and ventilatory ( vs . slope) and sympathetic (MSNA vs . slope) chemoreflex sensitivities and recruitment thresholds (breakpoint) were calculated. Global cerebral blood flow (gCBF duplex Doppler) was measured, and the association with chemoreflex responses was examined. Central ventilatory and sympathetic chemoreflex sensitivities were greater in HTN than NT (2.48 ± 1.33 vs . 1.58 ± 0.42 L min −1 mmHg −1 , P = 0.030: 3.32 ± 1.90 vs . 1.77 ± 0.62 a.u. mmHg −1 , P = 0.034, respectively), while recruitment thresholds were not different between groups. HTN and NT had similar combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities and recruitment thresholds. A lower gCBF was associated with an earlier recruitment threshold for ( R 2 = 0.666, P 0.0001) and MSNA ( R 2 = 0.698, P = 0.004) during isoxic hyperoxic rebreathing. These findings indicate that central ventilatory and sympathetic chemoreflex sensitivities are augmented in human HTN and perhaps suggest that targeting the central chemoreflex may help some forms of HTN. image In human hypertension (HTN) increased peripheral chemoreflex sensitivity has been identified as a pathogenic feature, and in animal models of HTN, both central and peripheral chemoreflex sensitivities are reportedly augmented. In this study, the hypothesis was tested that both central and combined central and peripheral chemoreflex sensitivities are augmented in human HTN. We observed that both central ventilatory and sympathetic chemoreflex sensitivities were augmented in HTN compared to age‐matched normotensive controls, but no difference was found in the combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities. During central chemoreflex activation, the ventilatory and sympathetic recruitment thresholds were lower in those with lower total cerebral blood flow. These results indicate a potential contributory role of the central chemoreceptors in the pathogenesis of human HTN and support the possibility that therapeutic targeting of the central chemoreflex may help some forms of HTN.
Publisher: Wiley
Date: 29-01-2010
Publisher: Wiley
Date: 08-2013
DOI: 10.1002/PHY2.66
Publisher: American Physiological Society
Date: 03-2012
DOI: 10.1152/JAPPLPHYSIOL.00988.2011
Abstract: The present study examined the integrative effects of passive heating on cerebral perfusion and alterations in central motor drive. Eight participants underwent passive hyperthermia [0.5°C increments in core temperature (Tc) from normothermia (37 ± 0.3°C) to their limit of thermal tolerance (T-LIM 39.0 ± 0.4°C)]. Blood flow velocity in the middle cerebral artery (CBFv) and respiratory responses were measured continuously. Arterial blood gases and blood pressure were obtained intermittently. At baseline and each Tc level, supramaximal femoral nerve stimulation and transcranial magnetic stimulation (TMS) were performed to assess neuromuscular and cortical function, respectively. At T-LIM, measures were (in a randomized order) also made during a period of breathing 5% CO 2 gas to restore eucapnia (+5% CO 2 ). Mean heating time was 179 ± 51 min, with each 0.5°C increment in Tc taking 40 ± 10 min. CBFv was reduced by ∼20% below baseline from +0.5°C until T-LIM. Maximal voluntary contraction (MVC) of the knee extensors was decreased at T-LIM (−9 ± 10% P 0.05), and cortical voluntary activation (VA), assessed by TMS, was decreased at +1.5°C and T-LIM by 11 ± 8 and 22 ± 23%, respectively ( P 0.05). Corticospinal excitability (measured as the EMG response produced by TMS) was unaltered. Reductions in cortical VA were related to changes in ventilation (V̇e R 2 = 0.76 P 0.05) and partial pressure of end-tidal CO 2 (Pet CO 2 R 2 = 0.63 P 0.05) and to changes in CBFv ( R 2 = 0.61 P = 0.067). Interestingly, although CBFv was not fully restored, MVC and cortical VA were restored towards baseline values during inhalation of 5% CO 2 . These results indicate that descending voluntary drive becomes progressively impaired as Tc is increased, presumably due, in part, to reductions in CBFv and to hyperthermia-induced hyperventilation and subsequent hypocapnia.
Publisher: Wiley
Date: 14-06-2012
Publisher: American Physiological Society
Date: 08-2008
DOI: 10.1152/JAPPLPHYSIOL.00010.2008
Abstract: The influence of severe passive heat stress and hypohydration (Hypo) on cardiorespiratory and cerebrovascular function is not known. We hypothesized that 1) heating-induced hypocapnia and peripheral redistribution of cardiac output (Q̇) would compromise blood flow velocity in the middle cerebral artery (MCAv) and cerebral oxygenation 2) Hypo would exacerbate the hyperthermic-induced hypocapnia, further decreasing MCAv and 3) heating would reduce MCAv-CO 2 reactivity, thereby altering ventilation. Ten men, resting supine in a water-perfused suit, underwent progressive hyperthermia [0.5°C increments in core (esophageal) temperature (T C ) to +2°C] while euhydrated (Euh) or Hypo by 1.5% body mass (attained previous evening). Time-control (i.e., non-heat stressed) data were obtained on six of these subjects. Cerebral oxygenation (near-infrared spectroscopy), MCAv, end-tidal carbon dioxide (Pet CO 2 ) and arterial blood pressure, Q̇ (flow model), and brachial and carotid blood flows (CCA) were measured continuously each 0.5°C change in T C . At each level, hypercapnia was achieved through 3-min administrations of 5% CO 2 , and hypocapnia was achieved with controlled hyperventilation. At baseline in Hypo, heart rate, MCAv and CCA were elevated ( P 0.05 vs. Euh). MCAv-CO 2 reactivity was unchanged in both groups at all T C levels. Independent of hydration, hyperthermic-induced hyperventilation caused a severe drop in Pet CO 2 (−8 ± 1 mmHg/°C), which was related to lower MCAv (−15 ± 3%/°C R 2 = 0.98 P 0.001). Elevations in Q̇ were related to increases in brachial blood flow ( R 2 = 0.65 P 0.01) and reductions in MCAv ( R 2 = 0.70 P 0.01), reflecting peripheral distribution of Q̇. Cerebral oxygenation was maintained, presumably via enhanced O 2 -extraction or regional differences in cerebral perfusion.
Publisher: University of Bern
Date: 12-03-2019
Abstract: Background: Tibetans experience lose less aerobic exercise capacity in hypoxia compared to lowland Han. We tested if inhalation of iloprost (to counter hypoxic pulmonary vasoconstriction) and furosemide (to decrease afferent vagal traffic from pulmonary receptors) improve performance in hypoxia in Han compared to Tibetans. Methods: 8 Tibetans and 8 Han, living at 2,260 m, did incremental uphill treadmill running to exhaustion at ambient pressure on day 1, followed by three runs at 5,000 m (hypobaric chamber) after inhalation of iloprost (ILO), furosemide (FUR) or placebo (PLA), on different days in a counter-balanced order. Results: In Han the performance decrement from 2,260 m to 5,000 m was greater than in Tibetans (p .05). In Han iloprost improved performance at 5,000 m compared to placebo (p .05 vs. PLA) furosemide had no effects. In Tibetans there were no treatment effects. Peripheral O2saturations at peak exercise at 5,000 m, were higher by ~8 % in the Tibetans (p .05 vs. Han). Maximum heart rate was lowered by 13±6 bpm in Han at 5,000 m regardless of treatment compared to 2,260 m (p .05). Tibetans reached similar maximum heart rates ∼200 bpmat 5,000 m and 2,260 m, independent of treatment. Conclusions: The blunting of the exercise impairment in severe hypoxia in Han during maximal exercise after inhalation of iloprost suggests that hypoxic pulmonary vasoconstriction and right ventricular function are potential performance limiting factors in Han in hypoxia.
Publisher: Public Library of Science (PLoS)
Date: 21-11-2013
Publisher: Mary Ann Liebert Inc
Date: 06-2010
Abstract: There are several reports on syncope occurring following standing at high altitude (HA), yet description of the detailed physiological responses to standing at HA are lacking. We examined the hypothesis that appropriate physiological adjustments to upright posture would be compromised at HA (5050 m). Ten healthy volunteers stood up rapidly from supine rest, for 3 min, at sea level and at 5050 m. Beat-to-beat mean arterial blood pressure (MAP, Finometer), middle cerebral artery blood velocity (MCAv, Transcranial Doppler), end-tidal PCO(2) and PO(2), and heart rate (ECG) were recorded continuously. After 14 days at HA, baseline MAP and MCAv were not different to sea level, although HR was elevated. Neither the magnitude of initial ( 0.05). By 3 min of standing, MAP was restored to supine values both at sea level (-3 +/- 12 mmHg) and HA (4 +/- 10 mmHg), although there was more complete recovery of HR at sea level (+13 +/- 10 b.min(-1), p = 0.02 vs. + 23 +/- 10 b.min(-1), p = 0.01). Reduced MCAv at 3 min was comparable at sea level and altitude (both -16%). These data indicate that initial cardiovascular and cerebrovascular responses to standing are unaltered when partially acclimatized to HA.
Publisher: Frontiers Media SA
Date: 14-10-2015
Publisher: Frontiers Media SA
Date: 24-02-2021
DOI: 10.3389/FPHYS.2021.617954
Abstract: The Tibetans’ better aerobic exercise capacity at altitude remains ill-understood. We tested the hypothesis that Tibetans display better muscle and brain tissue oxygenation during exercise in hypoxia. Using near-infrared spectrometry (NIRS) to provide indices of tissue oxygenation, we measured oxy- and deoxy-hemoglobin ([O 2 Hb] and [HHb], respectively) responses of the vastus lateralis muscle and the right prefrontal cortex in ten Han Chinese and ten Tibetans during incremental cycling to exhaustion in a pressure-regulated chamber at simulated sea-level (air at 1 atm: normobaric normoxia) and 5,000 m (air at 0.5 atm: hypobaric hypoxia). Hypoxia reduced aerobic capacity by ∼22% in both groups ( d = 0.8, p & 0.001 vs. normoxia), while Tibetans consistently outperformed their Han Chinese counterpart by ∼32% in normoxia and hypoxia ( d = 1.0, p = 0.008). We found cerebral [O 2 Hb] was higher in Tibetans at normoxic maximal effort compared Han ( p = 0.001), while muscle [O 2 Hb] was not different ( p = 0.240). Hypoxic exercise lowered muscle [O 2 Hb] in Tibetans by a greater extent than in Han (interaction effect: p & 0.001 vs. normoxic exercise). Muscle [O 2 Hb] was lower in Tibetans when compared to Han during hypoxic exercise ( d = 0.9, p = 0.003), but not during normoxic exercise ( d = 0.4, p = 0.240). Muscle [HHb] was not different between the two groups during normoxic and hypoxic exercise ( p = 0.778). Compared to Han, our findings revealed a higher brain tissue oxygenation in Tibetans during maximal exercise in normoxia, but lower muscle tissue oxygenation during exercise in hypoxia. This would suggest that the Tibetans privileged oxygenation of the brain at the expense of that of the muscle.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.RESP.2011.12.004
Abstract: We tested the hypothesis that preventing the poikilocapnic response to high intensity exercise would increase the ventilatory response to exercise. We measured ventilatory variables in 10 healthy men during incremental cycling with and without inspired CO(2) (randomised order). Inspired CO(2) elevated resting ventilation (V(E)), tidal volume (V(T)), PETCO₂ and PETO₂ by 5 ± 5 L/min, 0.3 ± 0.2 L, 6 ± 3 mm Hg and 11 ± 7 mm Hg, respectively (P 0.05). During high intensity exercise, inspired CO(2) elevated PETCO₂ by 7 ± 2, 10 ± 4 and 11 ± 4 mm Hg at 80%, 90% and 100% VO₂ max, respectively (P 0.05). During high intensity exercise, inspired CO(2) elevated VT by 0.2 ± 0.3 L at 80%, 90% and 100% VO₂ max, respectively (P 0.05). These data suggest a progressively diminishing role of CO(2) chemoreception in the control of ventilation during maximal incremental exercise.
Publisher: American Physiological Society
Date: 04-2010
DOI: 10.1152/AJPREGU.00815.2009
Abstract: Humans with spinal cord injury have impaired cardiovascular function proportional to the level and completeness of the lesion. The effect on cerebrovascular function is unclear, especially for high-level lesions. The purpose of this study was to evaluate the integrity of dynamic cerebral autoregulation (CA) and the cerebrovascular reactivity in chronic tetraplegia (Tetra). After baseline, steady-state hypercapnia (5% CO 2 ) and hypocapnia (controlled hyperventilation) were used to assess cerebrovascular reactivity in 6 men with Tetra (C5–C7 lesion) and 14 men without [able-bodied (AB)]. Middle cerebral artery blood flow velocity (MCAv), cerebral oxygenation, arterial blood pressure (BP), heart rate (HR), cardiac output (Q̇ model flow), partial pressure of end-tidal CO 2 (Pet CO 2 ), and plasma catecholamines were measured. Dynamic CA was assessed by transfer function analysis of spontaneous fluctuations in BP and MCAv. MCAv pulsatility index (MCAv PI) was calculated as (MCAv systolic − MCAv diastolic )/MCAv mean and standardized by iding by mean arterial pressure (MAP). Resting BP, total peripheral resistance, and catecholamines were lower in Tetra ( P 0.05), and standardized MCAv PI was ∼36% higher in Tetra ( P = 0.003). Resting MCAv, cerebral oxygenation, HR, and Pet CO 2 were similar between groups ( P 0.05). Although phase and transfer function gain relationships in dynamic CA were maintained with Tetra ( P 0.05), coherence in the very low-frequency range (0.02–0.07 Hz) was ∼21% lower in Tetra ( P = 0.006). Full (hypo- and hypercapnic) cerebrovascular reactivity to CO 2 was unchanged with Tetra ( P 0.05). During hypercapnia, standardized MCAv PI reactivity was enhanced by ∼78% in Tetra ( P = 0.016). Despite impaired cardiovascular function, chronic Tetra involves subtle changes in dynamic CA and cerebrovascular reactivity to CO 2 . Changes are evident in coherence at baseline and MCAv PI during baseline and hypercapnic states in chronic Tetra, which may be indicative of cerebrovascular adaptation.
Publisher: American Physiological Society
Date: 09-2019
DOI: 10.1152/JAPPLPHYSIOL.01116.2018
Abstract: Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction, and increased NO has the potential to enhance cerebral blood flow (CBF). Dietary supplementation with sodium nitrate, a precursor of NO, could improve cerebrovascular function, but this has not been investigated. In 17 in iduals, we examined the effects of a 7-day supplementation of dietary nitrate (0.1 mmol·kg −1 ·day −1 ) on cerebrovascular function using a randomized, single-blinded placebo-controlled crossover design. We hypothesized that 7-day dietary nitrate supplementation increases CBF response to CO 2 (cerebrovascular CO 2 reactivity) and cerebral autoregulation (CA). We assessed middle cerebral artery blood velocity (MCAv) and blood pressure (BP) at rest and during CO 2 breathing. Transfer function analysis was performed on resting beat-to-beat MCAv and BP to determine CA, from which phase, gain, and coherence of the BP-MCAv data were derived. Dietary nitrate elevated plasma nitrate concentration by ~420% ( P 0.001) and lowered gain ( d = 1.2, P = 0.025) and phase of the BP-MCAv signal compared with placebo treatment ( d = 0.7, P = 0.043), while coherence was unaffected ( P = 0.122). Dietary nitrate increased the MCAv-CO 2 slope in a sex-specific manner (interaction: P = 0.016). Dietary nitrate increased the MCAv-CO 2 slope in men ( d = 1.0, P = 0.014 vs. placebo), but had no effect in women ( P = 0.919). Our data demonstrate that dietary nitrate greatly increased cerebrovascular CO 2 reactivity in healthy in iduals, while its effect on CA remains unclear. The selective increase in the MCAv-CO 2 slope observed in men indicates a clear sexual dimorphic role of NO in cerebrovascular function. NEW & NOTEWORTHY We found dietary nitrate supplementation improved the brain blood vessels’ response to CO 2 , cerebrovascular CO 2 reactivity, without affecting blood pressure in a group of healthy in iduals. Meanwhile, the effect of dietary nitrate on the relationship between blood pressure and brain blood flow, cerebral autoregulation, was inconclusive. The improvement in cerebrovascular CO 2 reactivity was only observed in the male participants, alluding to a sex difference in the effect of dietary nitrate on brain blood flow control. Our findings indicate that dietary nitrate could be an effective strategy to enhance cerebrovascular CO 2 reactivity.
Publisher: American Physiological Society
Date: 10-2012
DOI: 10.1152/JAPPLPHYSIOL.00463.2012
Abstract: We sought to determine the influence of sympathoexcitation on dynamic cerebral autoregulation (CA), cerebrovascular reactivity, and ventilatory control in humans at high altitude (HA). At sea level (SL) and following 3–10 days at HA (5,050 m), we measured arterial blood gases, ventilation, arterial pressure, and middle cerebral blood velocity (MCAv) before and after combined α- and β-adrenergic blockade. Dynamic CA was quantified using transfer function analysis. Cerebrovascular reactivity was assessed using hypocapnia and hyperoxic hypercapnia. Ventilatory control was assessed from the hypercapnia and during isocapnic hypoxia. Arterial Pco 2 and ventilation and its control were unaltered following blockade at both SL and HA. At HA, mean arterial pressure (MAP) was elevated ( P 0.01 vs. SL), but MCAv remained unchanged. Blockade reduced MAP more at HA than at SL (26 vs. 15%, P = 0.048). At HA, gain and coherence in the very-low-frequency (VLF) range (0.02–0.07 Hz) increased, and phase lead was reduced (all P 0.05 vs. SL). Following blockade at SL, coherence was unchanged, whereas VLF phase lead was reduced (−40 ± 23% P 0.01). In contrast, blockade at HA reduced low-frequency coherence (−26 ± 20% P = 0.01 vs. baseline) and elevated VLF phase lead (by 177 ± 238% P 0.01 vs. baseline), fully restoring these parameters back to SL values. Irrespective of this elevation in VLF gain at HA ( P 0.01), blockade increased it comparably at SL and HA (∼43–68% P 0.01). Despite elevations in MCAv reactivity to hypercapnia at HA, blockade reduced ( P 0.05) it comparably at SL and HA, effects we attributed to the hypotension and/or abolition of the hypercapnic-induced increase in MAP. With the exception of dynamic CA, we provide evidence of a redundant role of sympathetic nerve activity as a direct mechanism underlying changes in cerebrovascular reactivity and ventilatory control following partial acclimatization to HA. These findings have implications for our understanding of CBF function in the context of pathologies associated with sympathoexcitation and hypoxemia.
Publisher: American Physiological Society
Date: 03-2018
DOI: 10.1152/AJPREGU.00109.2017
Abstract: The purpose of this study was to identify the dose-dependent effects of heat strain and orthostasis [via lower body negative pressure (LBNP)], with and without mild hypohydration, on systemic function and cerebral perfusion. Eleven men (means ± SD: 27 ± 7 y body mass 77 ± 6 kg), resting supine in a water-perfused suit, underwent progressive passive heating [0.5°C increments in core temperature (T c esophageal to +2.0°C)] while euhydrated (EUH) or hypohydrated (HYPO 1.5–2% body mass deficit). At each thermal state, mean cerebral artery blood velocity (MCAv mean transcranial Doppler), partial pressure of end-tidal carbon dioxide ([Formula: see text]), heart rate (HR) and mean arterial blood pressure (MAP photoplethysmography) were measured continuously during LBNP (0, −15, −30, and −45 mmHg). Four subjects became intolerant before +2.0°C T c , unrelated to hydration status. Without LBNP, decreases in [Formula: see text] accounted fully for reductions in MCAv mean across all T c . With LBNP at heat tolerance (+1.5 or +2.0°C), [Formula: see text] accounted for 69 ± 25% of the change in MCAv mean . The HYPO condition did not affect MCAv mean or any cardiovascular variables during combined LBNP and passive heat stress (all P 0.13). These findings indicate that hypocapnia accounted fully for the reduction in MCAv mean when passively heat stressed in the absence of LBNP and for two- thirds of the reduction when at heat tolerance combined with LBNP. Furthermore, when elevations in T c are matched, mild hypohydration does not influence cerebrovascular or cardiovascular responses to LBNP, even when stressed by a combination of hyperthermia and LBNP.
Publisher: Elsevier BV
Date: 03-2010
Abstract: Patients with obstructive sleep apnea (OSA) are predisposed to instability in central ventilatory control during sleep. Increased instability, as reflected in an enhanced expired volume in per unit time loop gain, has been associated with a greater predisposition to upper airway collapse. Here, in an otherwise healthy patient with untreated mild OSA, we describe the further exacerbation of OSA after oral indomethacin administration. The subject was a control subject in part of a study to investigate the effects of altering cerebral blood flow (CBF) on ventilatory responses and sleep. He was administered either placebo or 100 mg of indomethacin orally with 20 mL of antacid 2.5 h before sleep on different days. He was studied overnight by polysomnography, arterial blood gases, and transcranial Doppler ultrasound. Administration of 100 mg of oral indomethacin prior to sleep resulted in an almost doubling of the apnea-hypopnea index (14 to 24/h), compared with placebo. This was due to an increase in apneas, rather than hypopneas. Following the indomethacin, changes in arterial blood gases were unremarkable, but both CBF as indexed using transcranial Doppler ultrasound and CBF reactivity to a steady-state change in CO(2) (CBF-CO(2)) reactivity were reduced, and the ventilatory response to CO(2) was elevated. CBF was also further reduced during nonrapid eye movement sleep following the indomethacin when compared with the control night. Indomethacin-induced reductions in CBF and CBF-CO(2) reactivity and related increases in ventilatory instability may lead to a greater predisposition to upper airway collapse and related apnea these factors may partly explain the exacerbation of OSA.
Publisher: Frontiers Media SA
Date: 11-06-2014
Publisher: American Physiological Society
Date: 10-2023
DOI: 10.1152/JAPPLPHYSIOL.00100.2023
Abstract: Introduction: Acute altitude exposure lowers arterial oxygen content (CaO 2 ) and cardiac output ( c) at peak exercise, whilst O 2 extraction from blood to working muscles remains similar. Acclimatization normalizes CaO 2 but not peak c nor peak oxygen consumption ( O 2 p). To what extent acclimatization impacts muscle O 2 extraction remains unresolved. Methods: Twenty-one sea-level residents performed an incremental cycling exercise to exhaustion near sea level (SL), in acute (ALT1) and chronic (ALT16) hypoxia (5,260 m). Arterial blood gases, gas exchange at the mouth and oxy- (O 2 Hb) and deoxyhaemoglobin (HHb) of the vastus lateralis were recorded to assess arterial O 2 content (CaO 2 ), c, and O 2 . The HHb- O 2 slope was taken as a surrogate for muscle O 2 extraction. Results: During moderate-intensity exercise, HHb- O 2 slope increased to a comparable extent at ALT1 (2.13 ± 0.94) and ALT16 (2.03 ± 0.88) compared to SL (1.27 ± 0.12), indicating increased O 2 extraction. However, the HHb/CaO 2 ratio increased from SL to ALT1 and then tended to go back to SL values at ALT16. During high-intensity exercise, HHb- O 2 slope reached a break point beyond which it decreased at SL and ALT1, but not at ALT16. Discussion/Conclusion: Increased muscle O 2 extraction during submaximal exercise was associated with decreased CaO 2 in acute hypoxia. The significantly greater muscle O 2 extraction during maximal exercise in chronic hypoxia is suggestive of an O 2 reserve.
Publisher: American Physiological Society
Date: 06-2010
DOI: 10.1152/AJPREGU.00721.2009
Abstract: Indomethacin (INDO), a reversible cyclooxygenase inhibitor, is a useful tool for assessing the role of cerebrovascular reactivity on ventilatory control. Despite this, the effect of INDO on breathing stability during wakefulness has yet to be examined. Although the effect of reductions in cerebrovascular CO 2 reactivity on ventilatory CO 2 sensitivity is likely dependent upon the method used, no studies have compared the effect of INDO on steady-state and modified rebreathing estimates of ventilatory CO 2 sensitivity. The latter method includes the influence of Pco 2 gradients and cerebral perfusion, whereas the former does not. We examined the hypothesis that INDO-induced reduction in cerebrovascular CO 2 reactivity would 1) cause unstable breathing in conscious humans and 2) increase ventilatory CO 2 sensitivity during the steady-state method but not during rebreathing methods. We measured arterial blood gases, ventilation (V̇e), and middle cerebral artery velocity (MCAv) before and 90 min following INDO ingestion (100 mg) or placebo in 12 healthy participants. There were no changes in resting arterial blood gases or V̇e following either intervention. INDO increased the magnitude of V̇e variability (index of breathing stability) during spontaneous air breathing (+4.3 ± 5.2 Δl/min, P = 0.01) and reduced MCAv (−25 ± 19%, P 0.01) and MCAv-CO 2 reactivity during steady-state (−47 ± 27%, P 0.01) and rebreathing (−32 ± 25%, P 0.01). The V̇e-CO 2 sensitivity during the steady-state method was increased with INDO (+0.5 ± 0.5 l·min −1 ·mmHg −1 , P 0.01), while no changes were observed during rebreathing ( P 0.05). These data indicate that the net effect of INDO on ventilatory control is an enhanced ventilatory loop gain resulting in increased breathing instability. Our findings also highlight important methodological and physiological considerations when assessing the effect of INDO on ventilatory CO 2 sensitivity, whereby the effect of INDO-induced reduction of cerebrovascular CO 2 reactivity on ventilatory CO 2 sensitivity is unmasked with the rebreathing method.
Publisher: Springer Science and Business Media LLC
Date: 09-02-2014
DOI: 10.1007/S00421-014-2835-8
Abstract: The Richalet hypoxia sensitivity test (RT), which quantifies the cardiorespiratory response to acute hypoxia during exercise at an intensity corresponding to a heart rate of ~130 bpm in normoxia, can predict susceptibility of altitude sickness. Its ability to predict exercise performance in hypoxia is unknown. Investigate: (1) whether cerebral blood flow (CBF) and cerebral tissue oxygenation (O2Hb oxygenated hemoglobin, HHb deoxygenated hemoglobin) responses during RT predict time-trial cycling (TT) performance in severe hypoxia (2) if subjects with blunted cardiorespiratory responses during RT show greater impairment of TT performance in severe hypoxia. Thirteen men [27 ± 7 years (mean ± SD), Wmax: 385 ± 30 W] were evaluated with RT and the results related to two 15 km TT, in normoxia and severe hypoxia (FIO2 = 0.11). During RT, mean middle cerebral artery blood velocity (MCAv: index of CBF) was unaltered with hypoxia at rest (p > 0.05), while it was increased during normoxic (+22 ± 12 %, p < 0.05) and hypoxic exercise (+33 ± 17 %, p < 0.05). Resting hypoxia lowered cerebral O2Hb by 2.2 ± 1.2 μmol (p < 0.05 vs. resting normoxia) hypoxic exercise further lowered it to -7.6 ± 3.1 μmol below baseline (p < 0.05). Cerebral HHb, increased by 3.5 ± 1.8 μmol in resting hypoxia (p < 0.05), and further to 8.5 ± 2.9 μmol in hypoxic exercise (p 0.05 and R = 0.5, p > 0.05, respectively), while tissue oxygenation and SaO2 changes during TT did (R = -0.76, p < 0.05). Significant correlations were observed between SaO2, MCAv and HHb during RT (R = -0.77, -0.76 and 0.84 respectively, p < 0.05 in all cases). CBF and cerebral tissue oxygenation changes during RT do not predict performance impairment in hypoxia. Since the changes in SaO2 and brain HHb during the TT correlated with performance impairment, the hypothesis that brain oxygenation plays a limiting role for global exercise in conditions of severe hypoxia remains to be tested further.
Publisher: Mary Ann Liebert Inc
Date: 11-08-2023
Publisher: SAGE Publications
Date: 05-11-2021
DOI: 10.1177/0271678X211058261
Abstract: The ischemic penumbra is sensitive to alterations in cerebral perfusion. A myriad of drugs are used in acute ischemic stroke (AIS) management, yet their impact on cerebral hemodynamics is poorly understood. As part of the Cerebral Autoregulation Network led INFOMATAS project ( Identifying New Targets for Management and Therapy in Acute Stroke), this paper reviews some of the most common drugs a patient with AIS will come across and their potential influence on cerebral hemodynamics with a particular focus being on cerebral autoregulation (CA). We first discuss how compounds that promote clot lysis and prevent clot formation could potentially impact cerebral hemodynamics, before focusing on how the different classes of antihypertensive drugs can influence cerebral hemodynamics. We discuss the different properties of each drug and their potential impact on cerebral perfusion and CA. With emerging interest in CA status of AIS patients, either during or soon after treatment when timely reperfusion and salvageable tissue is at its most critical, the properties of these pharmacological agents may be relevant for modelling cerebral perfusion accuracy and for setting in idualised treatment strategies.
Publisher: American Physiological Society
Date: 06-2023
DOI: 10.1152/JAPPLPHYSIOL.00670.2022
Abstract: Hypertension remains a significant global health problem. Although hypertension research and therapies are keenly focused on the heart and arterial circulation, the venous circulation has been neglected comparatively. We determined whether hypoxia, known to cause peripheral chemoreflex activation, evoked more pronounced changes in lower limb venous capacity and compliance in hypertensives (HTN) than in age-matched normotensives (NT). We found that hypoxia reduced venous capacity in the great saphenous vein in HTN and increased its compliance twofold. However, hypoxia did not affect venous function in NT. Our data indicate the venomotor response to hypoxia is enhanced in hypertension, and this may contribute to the hypertensive state.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2009
DOI: 10.1007/S00421-009-1298-9
Abstract: Skin surface cooling has been shown to improve orthostatic tolerance however, the influence of severe heat stress on cardiovascular and cerebrovascular responses to skin cooling remains unknown. Nine healthy males, resting supine in a water-perfusion suit, were heated to +1.0 and +2.0 degrees C elevation in body core temperature (T (c)). Blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasound), mean arterial pressure (MAP photoplethysmography), stroke volume (SV Modelflow), total peripheral resistance (TPR Modelflow), heart rate (HR ECG) and the partial pressure of end-tidal carbon dioxide (P(ET)CO(2)) were measured continuously during 1-min baseline and 3-min lower body negative pressure (LBNP, -15 mm Hg) when heated without and again with skin surface cooling. Nine participants tolerated +1 degrees C and six participants reached +2 degrees C. Skin cooling elevated (P = 0.004) MAP ~4% during baseline and LBNP at +1 degrees C T (c). During LBNP, skin cooling increased SV (9% P = 0.010) and TPR (0.9 mm Hg L(-1) min, P = 0.013) and lowered HR (13 b min(-1), P = 0.012) at +1 degrees C T (c) and +2 degrees C T (c) collectively. At +2 degrees C T (c), skin cooling elevated P(ET)CO(2) ~4.3 mm Hg (P = 0.011) and therefore reduced cerebral vascular resistance ~0.1 mm Hg cm(-1) s at baseline and LBNP (P = 0.012). In conclusion, skin cooling under severe heating and mild orthostatic stress maintained cerebral blood flow more effectively than it did under moderate heating, in conjunction with elevated carbon dioxide pressure, SV and arterial resistance.
Start Date: 2017
End Date: 2020
Funder: Maurice and Phyllis Paykel Trust
View Funded ActivityStart Date: 2022
End Date: 2027
Funder: Health Research Council of New Zealand
View Funded ActivityStart Date: 2015
End Date: 2018
Funder: National Heart Foundation of New Zealand
View Funded ActivityStart Date: 2017
End Date: 2019
Funder: Wellington Medical Research Foundation
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