Posterior Cerebral Artery Velocity Research Articles

Neurovascular Coupling in Acutely Concussed Adolescent Patients.

Neurovascular coupling (NVC) uniquely describes cerebrovascular response to neural activation and has demonstrated impairments following concussion in adult patients. It is currently unclear how adolescent patients experience impaired NVC acutely following concussion during this dynamic phase of physiological development. The purpose of this study was to investigate NVC in acutely concussed adolescent patients relative to controls. We recruited patients presenting to a sports medicine practice within 28 days of a concussion or a musculoskeletal injury (controls). Transcranial Doppler ultrasound was used to measure changes in patients' posterior cerebral artery (PCA) velocity in response to two progressively challenging visual tasks: (1) reading and (2) visual search. Each task was presented in five 1-min trials (20 sec eyes closed/40 sec eyes open). Resting PCA velocity data were derived by averaging PCA velocity across a 2-min baseline period that preceded the visual tasks. Filtered task data were converted to time-series curves representing 40 consecutive 1-sec averages for each trial. Curves were then averaged across the five trials and time-aligned to stimulus onset (eyes open) to generate a single ensemble-averaged 40-sec curve representing NVC response for each participant for each task. Independent t tests were used to assess group differences (concussion vs. control) in resting PCA velocity. Separate linear mixed-effects models were used to evaluate group differences (concussion vs. control) in NVC response profiles for both visual tasks and group-by-task interaction. Twenty-one concussion patients (female = 8 [38.1%]; age = 14.4 ± 1.9 years) and 20 controls (female = 7 [35.0%]; age = 14.4 ± 1.9 years) were included in our analysis. Average resting PCA velocity did not significantly differ between concussion patients (36.6 ± 8.0 cm/sec) and controls (39.3 ± 8.5 cm/sec) (t39 = 1.06; p = 0.30). There were no significant group differences in relative NVC response curves during the reading task (F1,1560 = 2.23; p = 0.14) or the visual search task (F1,1521 = 2.04; p = 0.15). In contrast, the differential response to task (e.g., increase from reading task to visual search task) was significantly greater in concussion patients than in controls (p < 0.0001). The NVC response to the visual search task was 7.1% higher than the response to reading in concussion patients relative to being 5.5% higher in controls. Our data indicate that concussed patients present with a significantly greater response to more difficult tasks than do controls, suggesting that concussed adolescents require increased neural resource allocation as task difficulty increases. The study provides insight into the neurophysiological consequences of concussion in adolescent patients.

Exposure to passive heat and cold stress differentially modulates cerebrovascular-CO2 responsiveness.

Heat and cold stress influence cerebral blood flow (CBF) regulatory factors (e.g., arterial CO2 partial pressure). However, it is unclear whether the CBF response to a CO2 stimulus (i.e., cerebrovascular-CO2 responsiveness) is maintained under different thermal conditions. This study aimed to compare cerebrovascular-CO2 responsiveness between normothermia, passive heat, and cold stress conditions. Sixteen participants (8 females; 25 ± 7 yr) completed two experimental sessions (randomized) comprising normothermic and either passive heat or cold stress conditions. Middle and posterior cerebral artery velocity (MCAv, PCAv) were measured during rest, hypercapnia (5% CO2 inhalation), and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 mmHg). The linear slope of the cerebral blood velocity (CBv) response to changing end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness, and cerebrovascular conductance (CVC) was used to examine responsiveness independent of blood pressure. CBv-CVC-CO2 responsiveness to hypocapnia was greater during heat stress compared with cold stress (MCA: +0.05 ± 0.08 cm/s/mmHg/mmHg, P = 0.04; PCA: +0.02 ± 0.02 cm/s/mmHg/mmHg, P = 0.002). CBv-CO2 responsiveness to hypercapnia decreased during heat stress (MCA: -0.67 ± 0.89 cm/s/mmHg, P = 0.02; PCA: -0.64 ± 0.62 cm/s/mmHg; P = 0.01) and increased during cold stress (MCA: +0.98 ± 1.33 cm/s/mmHg, P = 0.03; PCA: +1.00 ± 0.82 cm/s/mmHg; P = 0.01) compared with normothermia. However, CBv-CVC-CO2 responsiveness to hypercapnia was not different between thermal conditions (P > 0.08). Overall, passive heat, but not cold, stress challenges the maintenance of cerebral perfusion. A greater cerebrovascular responsiveness to hypocapnia during heat stress likely reduces an already impaired cerebrovascular reserve capacity and may contribute to adverse events (e.g., syncope).NEW & NOTEWORTHY This study demonstrates that thermoregulatory-driven perfusion pressure changes, from either cold or heat stress, impact cerebrovascular responsiveness to hypercapnia. Compared with cold stress, heat stress poses a greater challenge to the maintenance of cerebral perfusion during hypocapnia, challenging cerebrovascular reserve capacity while increasing cerebrovascular-CO2 responsiveness. This likely exacerbates cerebral hypoperfusion during heat stress since hyperthermia-induced hyperventilation results in hypocapnia. No regional differences in middle and posterior cerebral artery responsiveness were found with thermal stress.

NEUROVASCULAR COUPLING AND CEREBROVASCULAR HAEMODYNAIMCS ARE MODIFIED BY EXERCISE TRAINING STATUS AT DIFFERENT STAGES OF MATURATION DURING YOUTH.

Neurovascular coupling (NVC) is mediated via nitric oxide signalling, which is independently influenced by sex hormones and exercise training. Whether exercise training differentially modifies NVC pre- vs. post-puberty, where levels of circulating sex hormones will differ greatly within- and between-sexes, remains to be determined. Therefore, we investigated the influence of exercise training-status on resting intra-cranial haemodynamics and NVC at different stages of maturation. Posterior and middle cerebral artery velocities (PCAv and MCAv) and pulsatility index (PCAPI and MCAPI) were assessed via trans-cranial Doppler ultrasound at rest and during visual NVC stimuli. N=121 exercise-trained (males: n=32, females: n=32) and untrained (males: n=28, females: n=29) participants were characterised as pre- (males: n=33, females: n=29) or post- (males: n=27, females: n=32) peak height velocity (PHV). Exercise-trained youth demonstrated higher resting MCAv (P=0.010). Maturity- and training-status did not affect the ∆PCAv and ∆MCAv during NVC. However, pre-PHV untrained males (19.4±13.5 vs. 6.8±6.0%; P≤0.001) and females (19.3±10.8 vs. 6.4±7.1%; P≤0.001) had a higher ∆PCAPI during NVC than post-PHV untrained counterparts, while the ∆PCAPI was similar in pre- and post-PHV trained youth. Pre-PHV untrained males (19.4±13.5 vs. 7.9±6.0%; P≤0.001) and females (19.3±10.8 vs 11.1±7.3%; P=0.016) also had a larger ∆PCAPI than their pre-PHV trained counterparts during NVC, but the ∆PCAPI was similar in trained and untrained post-PHV youth. Collectively, our data indicate that exercise training elevates regional cerebral blood velocities during youth, but training-mediated adaptations in NVC are only attainable during early stages of adolescence. Therefore, childhood provides a unique opportunity for exercise-mediated adaptations in NVC.

Menstrual phase influences cerebrovascular responsiveness in females but may not affect sex differences.

Background and aims: Sex differences in the rate and occurrence of cerebrovascular diseases (e.g., stroke) indicate a role for female sex hormones (i.e., oestrogen and progesterone) in cerebrovascular function and regulation. However, it remains unclear how cerebrovascular function differs between the sexes, and between distinct phases of the menstrual cycle. This study aimed to compare cerebrovascular-CO2 responsiveness in 1) females during the early follicular (EF), ovulatory (O) and mid-luteal (ML) phases of their menstrual cycle; and 2) males compared to females during phases of lower oestrogen (EF) and higher oestrogen (O). Methods: Eleven females (25 ± 5years) complete experimental sessions in the EF (n = 11), O (n = 9) and ML (n = 11) phases of the menstrual cycle. Nine males (22 ± 3years) completed two experimental sessions, approximately 2weeks apart for comparison to females. Middle and posterior cerebral artery velocity (MCAv, PCAv) was measured at rest, during two stages of hypercapnia (2% and 5% CO2 inhalation) and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 and 24mmHg). The linear slope of the cerebral blood velocity response to changes in end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness.. Results: In females, MCAv-CO2 responsiveness to hypocapnia was lower during EF (-.78 ± .45cm/s/mmHg) when compared to the O phase (-1.17 ± .52cm/s/mmHg; p < .05) and the ML phase (-1.30 ± .82; p < .05). MCAv-CO2 responsiveness to hypercapnia and hypo-to-hypercapnia, and PCAv-CO2 responsiveness across the CO2 range were similar between menstrual phases (p ≥ .20). MCAv-CO2 responsiveness to hypo-to hypercapnia was greater in females compared to males (3.12 ± .91cm/s/mmHg vs. 2.31 ± .46cm/s/mmHg; p = .03), irrespective of menstrual phase (EF or O). Conclusion: Females during O and ML phases have an enhanced vasoconstrictive capacity of the MCA compared to the EF phase. Additionally, biological sex differences can influence cerebrovascular-CO2 responsiveness, dependent on the insonated vessel.

Cerebrovascular and blood pressure responses during voluntary apneas are larger than rebreathing.

Both voluntary rebreathing (RB) of expired air and voluntary apneas (VA) elicit changes in arterial carbon dioxide and oxygen (CO2 and O2) chemostimuli. These chemostimuli elicit synergistic increases in cerebral blood flow (CBF) and sympathetic nervous system activation, with the latter increasing systemic blood pressure. The extent that simultaneous and inverse changes in arterial CO2 and O2 and associated increases in blood pressure affect the CBF responses during RB versus VAs are unclear. We instrumented 21 healthy participants with a finometer (beat-by-beat mean arterial blood pressure; MAP), transcranial Doppler ultrasound (middle and posterior cerebral artery velocity; MCAv, PCAv) and a mouthpiece with sample line attached to a dual gas analyzer to assess pressure of end-tidal (PET)CO2 and PETO2. Participants performed two protocols: RB and a maximal end-inspiratory VA. A second-by-second stimulus index (SI) was calculated as PETCO2/PETO2 during RB. For VA, where PETCO2 and PETO2 could not be measured throughout, SI values were calculated using interpolated end-tidal gas values before and at the end of the apneas. MAP reactivity (MAPR) was calculated as the slope of the MAP/SI, and cerebrovascular reactivity (CVR) was calculated as the slope of MCAv or PCAv/SI. We found that compared to RB, VA elicited ~ fourfold increases in MAPR slope (P < 0.001), translating to larger anterior and posterior CVR (P ≤ 0.01). However, cerebrovascular conductance (MCAv or PCAv/MAP) was unchanged between interventions (P ≥ 0.2). MAP responses during VAs are larger than those during RB across similar chemostimuli, and differential CVR may be driven by increases in perfusion pressure.

Does task complexity impact the neurovascular coupling response similarly between males and females?

BackgroundWhile previous studies have demonstrated a complex visual scene search elicits a robust neurovascular coupling (NVC) response, it is unknown how the duration of visual stimuli presentation influences NVC metrics. This study examined how stimuli duration, in addition to biological sex and self‐reported engagement impact NVC responses.MethodsParticipants (n = 20, female = 10) completed four visual paradigms. Three involved simple visual shapes presented at 0.5‐, 2‐, and 4‐s intervals in randomized orders. The fourth paradigm was a complex visual scene search (“Where's Waldo?”). Participants completed eight cycles of 20‐s eyes‐closed followed by 40‐s eyes‐open. Transcranial Doppler ultrasound indexed posterior and middle cerebral artery velocities (PCA and MCA). Participants self‐reported their engagement following each task (1 [minimal] to 10 [maximal]).ResultsThe “Where's Waldo?” task evoked greater PCA percent increase (all p < 0.001) and area under the curve during the first 30‐s of the task (all p < 0.001) compared to simple shapes. Females displayed greater absolute baseline and peak PCA and MCA velocities across all tasks (all p < 0.002). Subjective engagement displayed moderate correlation levels with PCA percent increase (Spearman ρ = 0.58) and area under the curve (Spearman ρ = 0.60) metrics in males, whereas these were weak for females (Spearman ρ = 0.43 and ρ = 0.38, respectively).ConclusionsThe complex visual paradigm “Where's Waldo?” greatly augmented the signal‐to‐noise ratio within the PCA aspects of the NVC response compared to simple shapes. While both sexes had similar NVC responses, task engagement was more related to NVC metrics in males compared to females. Therefore, future NVC investigations should consider task engagement when designing studies.

Cerebral Blood Flow Pulsatility Index is Unchanged during Superimposed Lower‐Body Negative Pressure in Head‐Up Tilt in Anterior and Posterior Cerebral Circulations

Lower body negative pressure (LBNP) chambers can be utilized to experimentally-elicit reductions in blood pressure, cerebral blood flow (CBF) and associated symptoms of presyncope. There is high between-individual variability in tolerance to LBNP, however the underlying physiological responses affecting tolerance remains unclear. Pulsatility in CBF may affect LBNP tolerance, as more pulsatile flow may protect the delivery of oxygen to cerebral tissues in hypotension. We aimed to assess the pulsatility index (PI) in anterior and posterior cerebral circulations during LBNP in superimposed head-up tilt (HUT), where gravitational-induced blood volume re-distribution augments volume unloading during LBNP. We recruited and included 12 healthy male participants, and instrumented them in a custom-build integrated 45° HUT-LBNP chamber. Participants were instrumented for heart rate (HR; ECG), end-tidal CO2 (PETCO2; mouthpiece and gas analyzer),beat-by-beat mean arterial pressure (MAP; finometer), and middle and posterior cerebral artery velocity (MCAv, PCAv; transcranial Doppler ultrasound). All measures were recorded during baseline (BL) and during -50 mmHg LBNP exposure up to a maximum of 10-minutes (600s). Presyncope was defined as a 30% reduction in systolic blood pressure (i.e., investigator stop) or onset subjective symptoms (i.e., participant stop). We quantified all variables as a 30-sec mean bin during BL and the final 30-sec of LBNP prior to presyncope. MAP, MCAv and PCAv PI was calculated as systolic-diastolic/mean. LBNP tolerance time was 480.9±134.3 sec. HR increased from 72.3±10.3 (BL) to 103.0±18.2 bpm (P<0.01) during LBNP, suggesting a baroreflex response, and PETCO2 was reduced from 32.0±2.9 (BL) to 28.7±2.9 Torr (P<0.01) during LBNP, suggesting mild hyperventilation. MAP decreased from 84.8±11.3 (BL) to 76.2±14.7 mmHg (P<0.01) during LBNP, with associated reductions in mean MCAv from 52.1±15.0 to 44.3±14.5 cm/s (P<0.01), and mean PCAv from 35.5±12.6 to 29.0±9.9 cm/s (P<0.01) during LBNP. MAP PI was reduced from 0.76±0.2 to 0.59±0.02 (P<0.01) during LBNP. However, MCAv and PCAv PI were unchanged during LBNP (P=0.6 and P=0.9, respectively). Our results suggest that although MAP and MAP PI were both reduced during LBNP at pre-syncope, with associated reductions in mean MCAv and PCAv, MCAv and PCAv PI remained stable with LBNP in HUT. These findings suggest that PI in CBF variables at the cardiac frequency are not related to LBNP tolerance in healthy men.

Cerebrovascular Responses During Voluntary Breath Holding are Larger than Rebreathing

Both voluntary breath-holding and rebreathing of expired air elicit changes in respiratory gas chemostimuli (CO2 and O2) at the metabolic rate. These chemostimuli elicit increases in cerebral blood flow (CBF), proportional to the magnitude of concomitant increases in CO2 and reductions in O2. These chemostimuli also activate the sympathetic nervous system, which increases systemic blood pressure. Although blood pressure responses appear small during rebreathing, evidence from obstructive sleep apnea (OSA) patients suggests higher mean blood pressure during sleep in those with worse OSA. We aimed to assess how superimposed changes in blood gases and increases in blood pressure affect the CBF responses during breath holding vs. rebreathing. We recruited 23 healthy participants (12 females) and instrumented them with a finometer (for beat-by-beat mean arterial blood pressure; MAP), transcranial Doppler ultrasound (middle and posterior cerebral artery velocity; MCAv, PCAv) and a pneumotachometer with gas sampling via a dual gas analyzer to assess the pressure of end-tidal (PET)CO2 and O2. Participants carried out two protocols in randomized order: (a) a maximal, voluntary end-inspiratory breath hold (BH) and (b) a rebreathing (RB) test. A breath-by-breath stimulus index (SI) was calculated as PETCO2/PETO2 during rebreathing, whereas the end-tidal gas values used to calculate SI were interpolated during breath holding from initial and break point values. During both BH and RB, cerebrovascular reactivity (CVR) was calculated as the MCAv or PCAv/SI. MAP reactivity (MAPR) was calculated as the slope of the MAP/SI response. Cerebrovascular conductance (CVC; MCA or PCA/MAP) reactivity (CVCR) was calculated as the slope of the MCACVC or PCACVC/SI responses. We found that (a) CVR was larger during BH vs. RB (MCA: 167.5±102.0 vs. 38.8±20.5 cm/s/SI, P<0.0001, n=23; PCA: 76.3±40.1 vs. 26.0±11.0 cm/s/SI, P<0.0001, n=19), (b) MAPR during BH was significantly higher than during RB (134.0±102.7 vs. 31.0±12.6 mmHg/SI, P=0.0001, n=23). and (c) CVCR during BH vs. RB (MCA: 0.75±0.69 vs. 0.16±0.15 cm/s/mmHg/SI, P<0.001, n=22; PCA: 0.26±0.29 vs. 0.12±0.09 cm/s/SI, cm/s/mmHg/SI, P=0.03, n=19). Our data demonstrate that breath holding elicited ~4-fold increases in MAP, translating to a larger anterior and posterior CVR compared to rebreathing. These findings suggest that the sympathetic responses during voluntary breath holding were larger than those during rebreathing across similar chemostimuli, potentially due to the differential sympathetic effects of struggling against a closed glottis during breath holding. This is the first evidence that voluntary apnea has larger effects on brain blood flow beyond that elicited by blood gas stimuli alone. Our data may have implications for understanding stroke risk in clinical populations with obstructive sleep apnea, whereby patients experience intermittent breath holds throughout the night, with associated spikes in arterial blood pressure.

Neurovascular Coupling is Unchanged during Sitting, Standing or Walking: Implications for Active Work Stations

Neurovascular coupling (NVC) is a phenomenon that matches regional cerebral blood flow to local neuronal metabolic activity. Improvements in NVC may underlie the qualitative reports of improved cognitive performance using standing and active workstations. However, little has been investigated pertaining to body position and the potential effects of sitting, standing or walking on NVC. We hypothesized that sitting, standing and low intensity treadmill walking (2 mph) would increase NVC magnitude in a dose-dependent fashion. We recruited 20 young, healthy participants (n=20, 11 females), and instrumented them with an electrocardiogram (beat-by-beat heart rate; HR; bpm), finger photoplethysmography (mean arterial pressure; MAP; mmHg) and transcranial Doppler ultrasound to quantify posterior cerebral artery velocity (PCAv; cm/s) during sitting, standing and walking trials. Each position included a protocol consisting of a 3-min baseline (BL) and three x 30-sec standardized visual stimulus (VS) periods using a 6 Hz strobe light held 15cm away from the eyes. Responses were quantified through (a) visually identified peak(s) PCAv during VS, (b) time to peak peak(s) and (c) mean PCAv response(s) during VS, with all three measures averaged for a representative response for each individual. NVC magnitude was then quantified as a change (delta) in peak and mean responses from BL. At baseline, HR was incrementally higher in sitting, standing and walking (P<0.001), but MAP was unchanged between positions (P=0.12). There were significant increases in the peak and mean responses from BL in all positions during VS (P<0.001), confirming an NVC response. However, there were no differences in delta peak (P=0.47), time-to-peak (P=0.29) nor delta mean (P=0.76) NVC responses during VS across all positions. These results suggest that NVC magnitude is unaffected by body position or low intensity physical activity. We conclude that reports of increased cognitive performance while using standing or active work stations in the workplace are not related to NVC, and are likely related to nervous system activation and/or changes in systemic metabolic rate.

Exercised state of mind: A perspective on ageing, cerebral blood flow and cognition.

Exercised state of mind: A perspective on ageing, cerebral blood flow and cognition.

Neurovascular Coupling in Special Operations Forces Combat Soldiers.

The purpose of this study was to investigate how concussion history affects neurovascular coupling in Special Operations Forces (SOF) combat Soldiers. We studied 100 SOF combat Soldiers [age = 33.5 ± 4.3 years; height = 180.4 ± 6.0 cm; 55 (55.0%) with self-reported concussion history]. We employed transcranial Doppler (TCD) ultrasound to assess neurovascular coupling (NVC) via changes in posterior cerebral artery (PCA) velocity in response to a reading and a visual search task. Baseline TCD data were collected for 2 min. NVC was quantified by the percent change in overall PCA response curves. We employed linear mixed effect models using a linear spline with one knot to assess group differences in percent change observed in the PCA velocity response curves between SOF combat Soldiers with and without a concussion history. Baseline PCA velocity did not significantly differ (t98 = 1.28, p = 0.20) between those with and without concussion history. Relative PCA velocity response curves did not differ between those with and without a concussion history during the reading task (F1,98 = 0.80, p = 0.37) or the visual search task (F1,98 = 0.52, p = 0.47). When assessing only SOF combat Soldiers with a concussion history, differential response to task was significantly greater in those with 3 or more concussions (F1,4341 = 27.24, p < 0.0001) relative to those with 1-2 concussions. Despite no main effect of concussion history on neurovascular coupling response in SOF combat Soldiers, we observed a dose-response based on lifetime concussion incidence. While long-term neurophysiological effects associated with head impact and blast-related injury are currently unknown, assessing NVC response may provide further insight into cerebrovascular function and overall physiological health.

Neurovascular coupling is not influenced by lower body negative pressure in humans.

Cerebral blood flow is tightly coupled with local neuronal activation and metabolism, i.e., neurovascular coupling (NVC). Studies suggest a role of sympathetic nervous system in the regulation of cerebral blood flow. However, this is controversial, and the sympathetic regulation of NVC in humans remains unclear. Since impaired NVC has been identified in several chronic diseases associated with a heightened sympathetic activity, we aimed to determine whether reflex-mediated sympathetic activation via lower body negative pressure (LBNP) attenuates NVC in humans. NVC was assessed using a visual stimulation protocol (5 cycles of 30 s eyes closed and 30 s of reading) in 11 healthy participants (aged 24 ± 3 yr). NVC assessments were made under control conditions and during LBNP at -20 and -40 mmHg. Posterior (PCA) and middle (MCA) cerebral artery mean blood velocity (Vmean) and vertebral artery blood flow (VAflow) were simultaneously determined with cardiorespiratory variables. Under control conditions, the visual stimulation evoked a robust increase in PCAVmean (∆18.0 ± 4.5%), a moderate rise in VAflow (∆9.6 ± 4.3%), and a modest increase in MCAVmean (∆3.0 ± 1.9%). The magnitude of NVC response was not affected by mild-to-moderate LBNP (all P > 0.05 for repeated-measures ANOVA). Given the small change that occurred in partial pressure of end-tidal CO2 during LBNP, this hypocapnia condition was matched via voluntary hyperventilation in absence of LBNP in a subgroup of participants (n = 8). The mild hypocapnia during LBNP did not exert a confounding influence on the NVC response. These findings indicate that the NVC is not influenced by LBNP or mild hypocapnia in humans.NEW & NOTEWORTHY Visual stimulation evoked a robust increase in posterior cerebral artery velocity and a modest increase in vertebral artery blood flow, i.e., neurovascular coupling (NVC), which was unaffected by lower body negative pressure (LBNP) in humans. In addition, although LBNP induced a mild hypocapnia, this degree of hypocapnia in the absence of LBNP failed to modify the NVC response.

The Effect of Acute Hypocapnia and Respiratory Alkalosis on Neurovascular Coupling Magnitude

The brain requires well‐regulated cerebrovascular perfusion to match local metabolic demand. Regional coupling of perfusion to metabolic rate is termed neurovascular coupling (NVC). NVC remains stable during blood gas perturbations upon ascent and acclimatization to altitude, where individuals are exposed to antagonistic effects of hypoxia (vasodilation) and hypocapnia (vasoconstriction), where acid‐base variables are likely well‐compensated. Few studies have addressed the effects of acute hypocapnia and respiratory alkalosis independently. The aim of this study was to assess the specific effects of acute steady‐state hypocapnia on NVC magnitude in a laboratory setting. We recruited 10 healthy participants and instrumented the posterior cerebral artery (PCA) with a transcranial Doppler ultrasound. NVC was elicited using a standardized strobe light stimulus (6 Hz; 5×30sec on/off), and both peak and mean absolute responses from baseline (BL) were quantified. Participants were coached to hyperventilate to reach steady‐state hypocapnic steps of Δ‐5 and Δ‐10 Torr end‐tidal (PET)CO2 from baseline levels. PETCO2 levels were significantly decreased from 36.7±4.2 (BL) to 31.0±5.1 and 25.9±5.4 Torr (P&lt;0.05), with estimated arterial pH(a) values of 7.43±0.05 (BL), 7.47±0.08 (Δ‐5) and 7.59±0.11 (Δ‐10), respectively (P&lt;0.05). There was a significant reduction in NVC magnitude from BL (10.2±2.5 cm/s) during controlled hypocapnia at both Δ‐5 (8.3±2.6 cm/s) and Δ‐10 (8.1±2.7 cm/s) in peak PCA velocity (PCAv) (P&lt;0.05), but no significant decrease in mean PCAv (P&gt;0.05). Our study demonstrates that acute respiratory alkalosis attenuates peak NVC magnitude with a floor effect at Δ‐5 Torr PETCO2 (~7.47 pHa), without further attenuation at Δ‐10 (~7.59 pHa). This is one of few studies demonstrating a change in NVC with acute blood gas challenges. However, the effect is small and only observed in peak PCAv responses, with no differences between mild and more severe respiratory alkalosis.Support or Funding InformationMRU Faculty of Science and Technology, University College Cork, University of Calgary

Cerebral hemodynamics among non-diabetic hemodialysis patients

BackgroundCerebrovascular accidents and cognitive impairment is a frequent complication of end-stage renal disease (ESRD) on regular hemodialysis (HD).ObjectiveTo evaluate cerebral circulation hemodynamics in non-diabetic prevalent hemodialysis patients by transcranial Doppler (TCD).Patients and methodsThe cross-sectional study included 50 ESRD patients on regular hemodialysis > 6 months in Ain Shams University Hospitals, Cairo, Egypt. Diabetic patients; chronic liver disease patients Child-Pugh class B or C; smokers; history of evident of cardiac, peripheral, or cerebrovascular insult; uncontrolled hypertension; anemia; collagen disease; and active infection were excluded from the study. An assessment of cerebral circulation hemodynamics by TCD in non-dialysis day to examine mean flow velocity (MFV) in the middle cerebral artery (MCA) and posterior cerebral artery (PCA).ResultsAn assessment of cerebral circulation hemodynamics revealed that 16 (32%) of the patients showed decrease MFV in MCA and 30 (60%) were normal. Regarding MFVs in PCA, 13 (26%) of the patients showed decrease MFVs, 33 (66%) were normal, and 4 (8%) of the patients failed due to poor bone window, significant reduction of MCV and PCA velocities in HD with urea reduction ratio < 65%, and a significantly negative correlation of MFV, PCA, and hemoglobin level (P < 0.05).ConclusionThere is a high frequency rate of decreased MCA and PCA MFV (32%, 28%), respectively, among non-diabetic prevalent hemodialysis patients with significant correlation to hemodialysis adequacy.

Cerebral blood flow responses to exercise are enhanced in left ventricular assist device patients after an exercise rehabilitation program.

Cerebral blood flow during exercise is impaired in patients with heart failure implanted with left ventricular assist devices (LVADs). Our aim was to determine whether a 3-mo exercise training program could mitigate cerebrovascular dysfunction. Internal carotid artery (ICA) blood flow and intracranial middle (MCAv) and posterior cerebral (PCAv) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental cycle ergometer exercise protocol in 12 LVAD participants (5 female, 53.6 ± 11.8 yr; 84.2 ± 15.7 kg; 1.73 ± 0.08) pre- (PreTR) and post- (PostTR) completion of a 3-mo supervised exercise rehabilitation program. At rest, only PCAv was different PostTR (38.1 ± 10.4 cm/s) compared with PreTR (43.0 ± 10.8 cm/s; P < 0.05). PreTR, the reduction in PCAv observed from rest to exercise (5.2 ± 1.8%) was mitigated PostTR (P < 0.001). Similarly, exercise training enhanced ICA flow during submaximal exercise (~8.6 ± 13.7%), resulting in increased ICA flow PostTR compared with a reduced flow PreTR (P < 0.001). Although both end-tidal partial pressure of carbon dioxide and mean arterial pressure responses during incremental exercise were greater PostTR than PreTR, only the improved was related to the improved ICA flow (R2 = 0.14; P < 0.05). Our findings suggest that short-term exercise training improves cerebrovascular function during exercise in patients with LVADs. This finding should encourage future studies investigating long-term exercise training and cerebral and peripheral vascular adaptation.NEW & NOTEWORTHY Left ventricular assist devices, now used as destination therapy in end-stage heart failure, enable patients to undertake rehabilitative exercise training. We show, for the first time in humans, that training improves cerebrovascular function during exercise in patients with left ventricular assist devices. This finding may have implications for cerebrovascular health in patients with heart failure.

Cerebrovascular function is preserved during mild hyperthermia in cervical spinal cord injury.

Experimental study. Compromised cerebrovascular function likely contributes to elevated neurological risk in spinal cord injury (SCI). Passive heating offers many cardiovascular and neurological health benefits; therefore, we aimed to determine the effects of an acute bout of heating on cerebrovascular function in chronic SCI. Persons with cervical SCI (n = 15) and uninjured controls (CON; n = 15) completed 60 min of lower limb hot water immersion (40 °C). Assessments of middle cerebral (MCA) and posterior cerebral artery (PCA) velocities, pulsatilities, and neurovascular coupling (NVC) were performed using transcranial Doppler ultrasound. Duplex ultrasonography was used to index cerebral blood flow via the internal carotid artery (ICA), and carotid-femoral pulse-wave velocity (PWV) was measured using tonometry. The NVC response was quantified as the peak hyperemic value during 30-s cycles of visual stimulation. Mean arterial pressure changed differentially with heating [mean (standard deviation); SCI: +6(14) mmHg, CON: -8(12) mmHg; P = 0.01]. There were no differences in any intracranial artery measures (all P > 0.05), except for small (~10%) increases in MCA conductance in CON after heating vs. SCI (interaction P = 0.006). Resting ICA flow was greater in SCI vs. CON (P = 0.03) but did not change with heating in either group (interaction P = 0.34). There were also no between-group differences in the NVC response (ΔPCA conductance) pre- [SCI: 29(19)% vs. CON: 30(9)%] or post-heating [SCI 30(9)% vs. 25(9)%; interaction P = 0.22]. Mild acute heating does not impair or improve cerebrovascular function in SCI or CON. Thus, further study of the effects of chronic heating interventions are warranted.

A Comparison of Protocols for Simulating Hemorrhage in Humans: Step vs. Ramp Lower Body Negative Pressure

IntroductionLower body negative pressure (LBNP) elicits central hypovolemia, and has been used to characterize the cardiovascular and cerebrovascular responses to simulated hemorrhage in humans. LBNP protocols traditionally employ a progressive stepwise reduction in pressure that is maintained for specific time periods. More recently, however, continuous ramp LBNP protocols have been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between a step LBNP protocol and a continuous ramp LBNP protocol until the onset of presyncope.MethodsHealthy human subjects (N=20; 8F, 12M) participated in two LBNP protocols to presyncope: 1) Step Protocol, where chamber pressure decreased every 5‐min to −15, −30, −45, −60, −70, −80, −90 and −100 mmHg, and, 2) Ramp Protocol, where chamber pressure decreased 3 mmHg/min. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), muscle and cerebral oxygen saturation (SmO2 and ScO2), and endtidal CO2 (etCO2) were measured continuously. Time to presyncope, the cumulative stress index (CSI; summation of chamber pressure*time at each pressure), and hemodynamic responses were compared between the two protocols.ResultsTime to presyncope (Step: 1611.8 ± 80.5 s vs. Ramp: 1675.4 ± 68.3 s; P=0.17), and the ensuing magnitude of central hypovolemia (%Δ SV, Step: −54.3 ± 2.5 % vs. Ramp: −51.9 ± 2.7 %; P=0.31) were similar between protocols, despite a higher CSI for the step protocol (Step: 946.5 ± 98.4 mmHg*min vs. Ramp: 836.7 ± 81.6 mmHg*min; P=0.06). While there were no differences at presyncope between protocols for the maximum change in HR, MCAv, or SmO2 (P≥0.21), the reduction in MAP was slightly less (Step: −17.1 ± 1.8 % vs. Ramp: −20.0 ± 1.4 %; P=0.02) and the reductions in PCAv, ScO2, and etCO2 (P≤0.08) were slightly greater for the step protocol compared to the ramp protocol.ConclusionThese results suggest that step and continuous ramp LBNP protocols elicit relatively similar tolerance times, reductions in central blood volume, and subsequent reflex hemodynamic responses, despite a greater cumulative stress in young healthy adults.Support or Funding InformationFunding for this study was provided by the U.S. Army MRMC Combat Casualty Care Research Program Grant # W81XWH‐11‐2‐0137. The content is solely the responsibility of the authors and does not necessarily represent the official views the US Department of Defense.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Changing Ischemic Lesion Patterns and Hemodynamics of the Posterior Cerebral Artery in Moyamoya Disease

The aim of this study was to determine how hemodynamics of the posterior cerebral artery (PCA) are associated with cerebral ischemic lesions in moyamoya disease (MMD). Thirty-six patients with ischemic MMD (Suzuki grade IV-V) were retrospectively analyzed. Hemodynamic parameters of the PCA were measured by transcranial color-coded sonography. We classified the range of ischemic lesions into 3 grades and perfusion levels into 3 grades according to computed tomography (CT) results. PCA steno-occlusion and leptomeningeal collaterals were confirmed by digital subtraction angiography. Ultrasonographic parameters in the PCA were compared with these radiographic findings. The velocity in the involved PCA (mean flow velocity [MFV] median, 42.00 [range, 34.50-58.00] cm/s) was significantly lower than that in the normal PCA (MFV median, 95.00 [range, 76.50-119.50] cm/s) (P < .001). The velocity in the PCA increased significantly as the leptomeningeal collateral stage advanced (MFV stage 1: median, 38.50 [range, 29.75-63.50] cm/s; stage 2: median, 55.00 [range, 44.00-96.00] cm/s; stage 3: median, 94.00 [range, 54.00-118.25] cm/s; stage 4: median, 85.50 [range, 70.50-117.75] cm/s, respectively) (P < .05). Decreased PCA velocities were associated with a larger ischemic area on CT (P ≤ .001). PCA velocity had no correlation with CT perfusion level of the temporal and frontal lobes. PCA velocity had significant correlations with perfusion level in the occipital (P < .001) and parietal lobes (P < .05). Our results suggest ischemic lesion patterns (as demonstrated on CT imaging) are associated with PCA velocity measurements in the advanced stage of MMD. Thus, monitoring PCA velocity in patients with advanced MMD may provide additional information to assist in managing these patients.

Neurovascular Coupling Remains Intact During Incremental Ascent to High Altitude (4240 m) in Acclimatized Healthy Volunteers.

Neurovascular coupling (NVC) is the temporal link between neuronal metabolic activity and regional cerebral blood flow (CBF), supporting adequate delivery of nutrients. Exposure to high altitude (HA) imposes several stressors, including hypoxia and hypocapnia, which modulate cerebrovascular tone in an antagonistic fashion. Whether these contrasting stressors and subsequent adaptations affect NVC during incremental ascent to HA is unclear. The aim of this study was to assess whether incremental ascent to HA influences the NVC response. Given that CBF is sensitive to changes in arterial blood gasses, in particular PaCO2, we hypothesized that the vasoconstrictive effect of hypocapnia during ascent would decrease the NVC response. 10 healthy study participants (21.7 ± 1.3 years, 23.57 ± 2.00 kg/m2, mean ± SD) were recruited as part of a research expedition to HA in the Nepal Himalaya. Resting posterior cerebral artery velocity (PCAv), arterial blood gasses (PaO2, SaO2, PaCO2, [HCO3-], base excess and arterial blood pH) and NVC response of the PCA were measured at four pre-determined locations: Calgary/Kathmandu (1045/1400 m, control), Namche (3440 m), Deboche (3820 m) and Pheriche (4240 m). PCAv was measured using transcranial Doppler ultrasound. Arterial blood draws were taken from the radial artery and analyzed using a portable blood gas/electrolyte analyzer. NVC was determined in response to visual stimulation (VS; Strobe light; 6 Hz; 30 s on/off × 3 trials). The NVC response was averaged across three VS trials at each location. PaO2, SaO2, and PaCO2 were each significantly decreased at 3440, 3820, and 4240 m. No significant differences were found for pH at HA (P > 0.05) due to significant reductions in [HCO3-] (P < 0.043). As expected, incremental ascent to HA induced a state of hypoxic hypocapnia, whereas normal arterial pH was maintained due to renal compensation. NVC was quantified as the delta (Δ) PCAv from baseline for mean PCAv, peak PCAv and total area under the curve (ΔPCAv tAUC) during VS. No significant differences were found for Δmean, Δpeak or ΔPCAv tAUC between locations (P > 0.05). NVC remains remarkably intact during incremental ascent to HA in healthy acclimatized individuals. Despite the array of superimposed stressors associated with ascent to HA, CBF and NVC regulation may be preserved coincident with arterial pH maintenance during acclimatization.

The Neurovascular Coupling Response Remains Intact During Incremental Ascent to High Altitude (4370m) in Acclimatized Healthy Volunteers

Neurovascular coupling (NVC) is the link between neuronal metabolic activity and regional cerebral blood flow. NVC is responsible for ensuring adequate delivery of nutrients (O2 and glucose) during periods of increased neuronal metabolic demand. Exposure to high‐altitude (HA) elicits ventilatory and acid‐base adjustments for maintaining blood pH. Acute exposure to HA causes hypoxic vasodilation. Hypoxia also drives a ventilatory response, inducing hypocapnia, a potent vasoconstrictor. Whether these dynamic and conflicting responses affect NVC during incremental ascent to HA is unclear.The aim of this project was to assess whether changes in arterial blood gases (ABGs) associated with ascent to HA influences the NVC response. Given that CBF is particularly sensitive to changes in PaCO2, we hypothesized that hypocapnic vasoconstriction during ascent would decrease the NVC response with ascent.10 healthy study participants (21.7±1.3 yrs, 70.46±13.65kg, mean±SD) were recruited as part of a research expedition to Everest base camp, Nepal. Resting posterior cerebral artery velocity (PCAv), ABGs (PaO2, PaCO2), SaO2, arterial blood pH and bicarbonate [HCO3−] were measured at four locations: Calgary (1045m; baseline; BL), Namche (3440m), Deboche (3820m) and Pheriche (4370m). Resting PCAv was measured using transcranial Doppler ultrasound. Arterial blood draws were taken from the radial artery and analysed using a portable blood gas/electrolyte analyser used to monitor changes in ABGs (PaCO2, PaO2, SaO2), pH and [HCO3−] during ascent. NVC was tested via visual stimulation (VS; Strobe light; 6Hz; 30sec on/off ×3). The NVC response was averaged across three VS trials at each location. NVC was quantified as the change (delta) in mean and peak PCAv from baseline, during VS.A one‐factor‐repeated measures analysis of variance (ANOVA) was used to assess for differences in baseline PCAv, NVC, ABGs, blood pH and [HCO3−] between locations. PaO2, PaCO2 and SaO2 were significantly decreased from BL at each altitude (P&lt;0.001, P&lt;0.016 and P&lt;0.013, respectively). No significant differences were found for pH at any location compared to BL (P&gt;0.05) due to reductions in arterial [HCO3−] (P&lt;0.043). No significant differences were found in baseline PCAv between locations (P&gt;0.05) or for mean or peak NVC responses (P&gt;0.085 and P&gt;0.08 respectively).As expected, incremental ascent to HA induced a state of hypoxic hypocapnia, as demonstrated by significant reductions in PaO2, SaO2 and PaCO2, whereas arterial pH was maintained via reductions in [HCO3−]. Our data suggests that NVC remains remarkably intact during incremental ascent to HA in healthy acclimatized individuals. Despite the array of superimposed stressors associated with ascent to HA, CBF and NVC regulation may be a unique function of arterial pH maintenance.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.