Middle Cerebral Artery Mean Blood Research Articles

Directional sensitivity of the cerebral pressure-flow relationship during forced oscillations induced by oscillatory lower body negative pressure.

A directional sensitivity of the cerebral pressure-flow relationship has been described using repeated squat-stands. Oscillatory lower body negative pressure (OLBNP) is a reproducible method to characterize dynamic cerebral autoregulation (dCA). It could represent a safer method to examine the directional sensitivity of the cerebral pressure-flow relationship within clinical populations and/or during pharmaceutical administration. Therefore, examining the cerebral pressure-flow directional sensitivity during an OLBNP-induced cyclic physiological stress is crucial. We calculated changes in middle cerebral artery mean blood velocity (MCAv) per alterations to mean arterial pressure (MAP) to compute ratios adjusted for time intervals (ΔMCAvT/ΔMAPT) with respect to the minimum-to-maximum MCAv and MAP, for each OLBNP transition (0 to -90 Torr), during 0.05 Hz and 0.10 Hz OLBNP. We then compared averaged ΔMCAvT/ΔMAPT during OLBNP-induced MAP increases (INC) (ΔMCAvT/) and decreases (DEC) (ΔMCAvT/). Nineteen healthy participants [9 females; 30 ± 6 years] were included. There were no differences in ΔMCAvT/ΔMAPT between INC and DEC at 0.05 Hz. ΔMCAvT/ (1.06 ± 0.35 vs. 1.33 ± 0.60 cm⋅s-1/mmHg; p = 0.0076) was lower than ΔMCAvT/ at 0.10 Hz. These results support OLBNP as a model to evaluate the directional sensitivity of the cerebral pressure-flow relationship.

Feasibility and preliminary efficacy of a theory-informed resistance exercise training single-arm intervention for major depression

Many adults with major depressive disorder (MDD) do not receive effective treatment. The potential benefits of resistance exercise training (RET) are understudied and may be mechanistically related to cerebral blood flow changes. PurposeTo assess feasibility, acceptability, and preliminary efficacy of a 16-week, theory-informed RET trial for the treatment of MDD and explore changes in cerebral blood flow. MethodsTen adults with DSM-5-diagnosed MDD were enrolled in a single-arm, 16-week, twice-weekly, whole-body RET intervention, consistent with US and WHO Physical Activity resistance exercise guidelines. To build intrinsic motivation and develop exercise-preparatory habits, motivators and commitment were discussed weekly. Screening, enrollment, and intervention attendance and compliance rates documented feasibility. At baseline and weeks 8, 16, and 26, current MDD diagnosis, clinician-rated, and self-reported symptom severity were evaluated along with cerebral blood flow which was assessed as middle cerebral artery (MCA) mean blood velocity, conductance, and pulsatility. ResultsNine participants completed the intervention. Strong feasibility and acceptability (98 % adherence, 93 % compliance, and 90 % retention) were found. MDD remission was reached by 8/9 participants at week 16 and persisted through week 26. There were large decreases in clinician-rated and self-reported symptoms at each assessment (Hedges’ g = 0.84–2.13). There were small-to-moderate increases in MCA velocity (g = 0.32–0.57) and conductance (g = 0.20–0.76) across time, with minimal changes in pulsatility (all g < 0.21). ConclusionsPreliminary results suggest RET for MDD treatment is feasible and plausibly efficacious, finding large antidepressant effects. A sufficiently powered randomized controlled trial to assess RET’s efficacy for treating MDD via potential cerebrovascular mechanisms is warranted.

Combined Transcranial Doppler and Melatonin Levels to Predict Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

To investigate the early prediction value of transcranial Doppler ultrasound (TCD) combined with serum melatonin level for delayed cerebral ischemia (DCI) caused by subarachnoid hemorrhage (SAH). This paper is a prospective study. A total of 120 patients with SAH treated were included. The patients were divided into the DCI group (40 cases) and non-DCI group (80 cases) according to whether DCI occurred 14 days after SAH (DCI usually occurs 4 to 14d after bleeding). Baseline data, serum melatonin level, and TCD test results within 24hours after admission were compared between the 2 groups. Multivariate logistic analysis was used to analyze the factors affecting the occurrence of DCI after SAH. The value of serum melatonin level, middle cerebral artery mean blood flow velocity (MBFV) and their combination in predicting DCI in SAH patients was evaluated. Univariate analysis showed that there were statistically significant differences in the proportion of Fisher grade, Hunt-Hess grade, serum melatonin level, middle cerebral artery systolic blood flow velocity (Vs), MBFV and pulse index (PI) between the 2 groups (P<0.05). Serum melatonin levels, middle cerebral artery Vs, MBFV, and PI in the DCI group were higher than those in non-DCI group. Logistic regression (LR) analysis showed that serum melatonin level (OR=1.796, 95% CI: 1.575-4.123) and middle cerebral artery MBFV (OR=3.279, 95% CI: 2.112-4.720] were the influencing factors for DCI in SAH patients (P<0.05). Middle cerebral artery MBFV and serum melatonin levels were higher in patients with SAH complicated with DCI, and the combination of the 2 could provide a reference for early clinical prediction of DCI in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Cool head-out water immersion does not alter cerebrovascular reactivity to hypercapnia despite elevated middle cerebral artery blood velocity: A pilot study.

Episodic increases in cerebral blood flow (CBF) are thought to contribute to improved cerebrovascular function and health. Head-out water immersion (HOWI) may be a useful modality to increase CBF secondary to the hydrostatic pressure placed on the body. However, it is unclear whether water temperatures common to the general public elicit similar cerebrovascular responses. We tested the hypothesis that mean middle cerebral artery blood velocity (MCAvmean) and cerebrovascular reactivity to CO2 (CVRCO2) would be higher during an acute bout of thermoneutral (TN; 35°C) vs. cool (COOL; 25°C) HOWI. Ten healthy participants (age: 23±3 y; 4 women) completed two randomized HOWI visits. Right MCAvmean, end-tidal CO2 (PETCO2) mean arterial pressure (MAP), and MCA conductance (MCAvmean/MAP) were continuously recorded. CVRCO2 was assessed using a stepped hypercapnia protocol before (PRE), at 30 minutes of HOWI (HOWI), immediately after HOWI (POST-1), and 45 minutes after HOWI (POST-2). Absolute values are reported as mean ± SD. MCAvmean, PETCO2, MAP, and CVRCO2 were not different between conditions at any timepoint (all P≥0.17). In COOL, MCAvmean increased from PRE (61±9 cm/s) during HOWI (68±11 cm/s), at POST-1 (69±11 cm/s), and POST-2 (72±8 cm/s) (all P<0.01), and in TN from PRE to POST-1 (66±13 vs. 71±14 cm/s; P = 0.05). PETCO2 did not change over time in either condition. In COOL, MAP increased from PRE (85±5 mmHg) during HOWI (101±4 mmHg), at POST-1 (97±7 mmHg), and POST-2 (96±9 mmHg), and in TN from PRE (88±5 mmHg) at HOWI (98±7 mmHg) and POST-1 (99±8 mmHg) (all P<0.01). In COOL, CVRCO2 increased from PRE to HOWI (1.66±0.55 vs. 1.92±0.52 cm/s/mmHg; P = 0.04). MCA conductance was not different between or within conditions. These data indicate that 30 minutes of cool HOWI augments MCAvmean and that the increase in MCAvmean persists beyond cool HOWI. However, cool HOWI does not alter CVRCO2 in healthy young adults.

Comparison of the Buffalo Concussion Treadmill Test With a Physiologically Informed Cycle Test: Calgary Concussion Cycle Test.

Sport-related concussions are a complex injury requiring multifaceted assessment, including physical exertion. Currently, concussion testing relies primarily on a treadmill-based protocol for assessing exertion-related symptoms in persons after concussion. This study compared a modified cycle protocol (Calgary Concussion Cycle Test [CCCT]) with the clinically adopted standard, the Buffalo Concussion Treadmill Test (BCTT), across multiple physiological parameters. Treadmill and cycle matched workload protocols would produce similar results for cerebral blood velocity, mean arterial pressure (MAP), and end-tidal carbon dioxide partial pressure (PETCO2), but heart rate (HR) and oxygen consumption (VO2) would be higher on the treadmill than the cycle modality. Crossover study design. Level 3. A total of 17 healthy adults (8 men, 9 women; age, 26 ± 3 years; body mass index, 23.8 ± 2.7 kg/m2) completed the BCTT and CCCT protocols, 7 days apart in a randomized order. During both exertional protocols, the physiological parameters measured were middle cerebral artery mean blood velocity (MCAv), MAP, PETCO2, VO2, and HR. Analysis of variance with effect size computations, coefficient of variation, and Bland-Altman plots with 95% limits of agreement were used to compare exercise tests. The BCTT and CCCT produced comparable results for both male and female participants with no significant differences for average MCAv, MAP, and PETCO2 (all P > 0.05; all generalized eta squared [η2G] < 0.02 [negligible]; P value range, 0.29-0.99) between stages. When accounting for exercise stage and modality, VO2 (P < 0.01) and HR (P < 0.01) were higher on the treadmill compared with the cycle. Aside from the final few stages, all physiology measures displayed good-to-excellent agreeability/variability. The CCCT was physiologically similar to the BCTT in terms of MCAv, PETCO2, and MAP; however, HR and VO2 differed between modalities. Providing a cycle-based modality to exertional testing after injury mayincrease accessibility to determine symptom thresholds in the future.

Older females but not males exhibit increases in cerebral blood velocity, despite similar pulsatility increases after high-intensity resistance exercise.

Sex differences in resting cerebral hemodynamics decline with aging. Acute resistance exercise (RE) is a hypertensive challenge that might reveal sex-dependent abnormalities in cerebral hemodynamics. Thus, we hypothesized cerebral blood velocity and pulsatility responses to RE would be sex-dependent in older adults. Fourteen older females and 11 males [50-68 years] completed a high-intensity unilateral isokinetic knee flexion/extension exercise. Measurements were collected at baseline, immediately, 5-and 30-min post-RE. Blood pressure was measured via finger photoplethysmography. Mean middle cerebral artery blood velocity (MCAv) and pulsatility were assessed via transcranial Doppler ultrasound. Carotid pulsatility was obtained via duplex ultrasound. MCAv increased immediately after RE in older females (mean difference (d)= 6.02, 95% CI: 1.66 to 10.39 cm. s-1, p<0.001) but not in males (d= -0.72, 95% CI: -3.83 to 5.27 cm.s-1, p=0.99). Followed by similar reductions 5-min post-RE in older females (d= -4.40, 95% CI: -8.81 to -0.10 cm.s-1, p=0.045) and males (d= -6.41, 95% CI: -11.19 to -1.62 cm.s-1, p=0.003). MCAv pulsatility increased similarly in older females (d= 0.24, 95% CI: 0.11 to 0.40, p<0.001) and males (d=0.38, 95% CI: 0.20 to 0.53, p<0.001), persisting 5-min post-RE. Older females showed smaller increases in carotid pulsatility immediately after RE (d= 0.18, 95% CI: 0.03 to 0.38, p=0.01) than males (d=0.48, 95% CI: 0.26 to 0.68, p<0.001). An exercise-mediated hypertensive stimulus revealed differential sex responses in MCAv and carotid pulsatility but not in cerebral pulsatility. Cerebral pulsatility findings suggests a similar sex susceptibility to cerebrovascular abnormalities following an exercise-mediated hypertensive stimulus in older adults.

Cerebral vascular function in young, healthy non-Hispanic Black and White females

Non-Hispanic Black (BL) individuals are ~2-times more likely to suffer from conditions including cognitive dysfunction and Alzheimer’s disease and related dementias (ADRD) – conditions which are among the fastest growing causes of morbidity and mortality in the US. The prevalence of ADRD is expected to double by 2060 with a more rapid increase in the BL (and Hispanic) population. Importantly, reduced vascular function, particularly in the cerebral circulation, contributes to elevated risk for and prevalence of ADRD. While previous research has provided valuable insight into mechanisms of cerebral vascular dysfunction, this work has been primarily conducted in males and has largely not included socioeconomic/racial discrimination measurements, which are critical to understanding race/ethnicity-related disparities in cerebral vascular health. To our knowledge no studies have specifically examined cerebral vascular function in young, healthy BL females relative to WH females. Therefore, we tested the hypothesis that cerebral vascular function would be blunted in BL relative to WH females. METHODS: Eleven healthy WH (age: 26±7 yr; BMI: 26±3 kg/m2) and 17 healthy (age: 21±2 yr; BMI: 26±4 kg/m2) BL females participated. Beat-to-beat blood pressure, end-tidal carbon dioxide tension, and middle cerebral artery mean blood velocity (MCAVmean) were continuously collected. Transfer function analysis (i.e. gain, phase, and coherence) of blood pressure and MCAVmean were calculated in the very-low, low, and high-frequency ranges to assess cerebral autoregulation. Cerebral vascular function was also assessed as the % increase in MCA vascular conductance (CVCi = MCAVmean/mean arterial pressure) during administration of a hypercapnic gas (6% CO2 gas). Socioeconomic background and psychosocial stress exposures were assessed as: 1) parental education level; 2) adverse childhood experiences (ACEs); and 3) perceived ethnic discrimination (PEDQ). RESULTS: Transfer function analysis of gain, phase, and coherence was similar across all frequency ranges ( P&gt;0.05 for all) and the % increase in CVCi ( P=0.71) during hypercapnia was similar between BL and WH females. Although perceived ethnic discrimination was greater in BL relative to WH females ( P&lt;0.001), there were no group differences in parental education level nor ACEs ( P&gt;0.05 for both). CONCLUSION: These preliminary data suggest that cerebral vascular function is not different between young, healthy BL and WH females of similar socioeconomic background. Future studies should continue to examine these relationships but expand inclusion to a wider age group with a greater diversity in socioeconomic background. Funding: NIH R15 (HL156128, RMB) &amp; AHA Predoctoral Fellowship (915133, ZTM) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Oral contraceptive use and menstrual cycle influence acute cerebrovascular response to standing.

To determine if the menstrual cycle and oral contraceptives (OC) influence responses to acute orthostatic stress and if these factors are clinically relevant to the diagnosis of initial orthostatic hypotension (iOH). Young, healthy women were recruited, including OC users (n=12) and non-users (NOC; n=9). Women were tested during the low hormone (LH; placebo pills; days 2-5 natural cycle) and high hormone (HH; active dose; days 18-24 natural cycle) menstrual phases. Changes in mean arterial pressure, cardiac output, heart rate, the 30:15 heart rate ratio and cerebrovascular resistance indices within 30s of standing were examined. There were no effects of OC or menstrual cycle on hemodynamic responses during standing (all p>0.05). In the LH phase, OC users had a greater fall in mean middle cerebral artery blood velocity (MCAV) compared to NOC (p<0.05). However, this was reversed in the HH phase, where OC users had a reduced fall in mean MCAV (p<0.05). Interestingly, 8 women (OC and NOC) had drops in systolic/diastolic blood pressure meeting the criteria for iOH, and 7 of those 8 women displayed this drop in a single phase of the menstrual cycle. Our results indicate that chronic versus acute OC use (i.e., long-term use observed via LH phase versus short-term use observed via HH phase) have opposing effects on cerebral blood velocity during standing. Further, our results highlight that multiple assessments across the cycle may be necessary to accurately diagnose iOH, as most women met the diagnostic criteria during a single menstrual phase.

The value of transcranial Doppler monitoring of cerebral blood flow changes during carotid endarterectomy performed under regional anesthesia - A case series.

Patients with unilateral hemodynamically significant carotid stenosis scheduled for elective CEAs were included. Ultrasound-guided intermediate plexus block was used for regional anesthesia. TCD monitoring of the middle cerebral artery mean blood flow velocity (MCAV) was performed throughout the procedure. MCAVs were offline analyzed during different phases of CEA: (1) resting state, before regional block, (2) after block, before incision, (3) before cross-clamp, (4) after cross-clamp, (5) 5 min after cross-clamp, (6) 10 min after cross-clamp, (7) after declamping, and (8) during the postoperative period (4-6 h). Shunt insertion based on the deterioration of neurological symptoms after cross-clamping was necessary for 11/66 patients (16.6%). In these symptomatic patients, the ipsilateral percent decrease of the MCAV was more than 70% in 8 out of 11 cases (72.7%). In asymptomatic patients, without shunt insertion, the average decrease of MCAV was less than 50%. Neurological symptoms referring to cerebral ischemia may be superior to TCD monitoring of cerebral blood flow for detecting the necessity of a shunt. Regional anesthesia enables reliable, symptom-based monitoring of CEAs.

Ingestion of carbonated water increases middle cerebral artery blood velocity and improves mood states in resting humans exposed to ambient heat stress

Sugar-free carbonated water is consumed worldwide. The consumption of carbonated water is high in summer, when the heat loss responses of sweating and skin vasodilation are activated, and thermal perceptions (thermal sensation and comfort) and mood states are negatively modulated. However, whether ingesting carbonated water under ambient heat exposure modulates cerebral blood flow index, heat loss responses, thermal perceptions, and mood states remains to be determined. In this study, 17 healthy, habitually active, young adults (eight women) ingested 4 °C noncarbonated or carbonated water under 37 °C ambient heat-stressed resting conditions. Both drinks increased the middle cerebral artery mean blood velocity, an index of cerebral blood flow, and mean arterial pressure, with carbonated water exhibiting higher elevations than noncarbonated water (P < 0.05). However, the heart rate, sweat rate, and skin blood flow during and after drinking remained unchanged between the two conditions (P > 0.05). The thermal sensation and comfort after drinking remained unchanged between the two conditions (P > 0.05); but, a drink-induced reduction in sleepiness was higher, and drink-induced elevations in motivation and exhilaration were higher after ingesting carbonated water than those after ingesting noncarbonated water (P < 0.05). The analyses suggest that in humans under ambient heat-stressed resting conditions, ingestion of cold carbonated water increases the cerebral blood flow index, blood pressure, motivation, and exhilaration, whereas it decreases sleepiness relative to ingestion of noncarbonated cold water. However, ingestion of cold carbonated water fails to modulate thermoregulatory responses and thermal perception as opposed to noncarbonated cold water.

Influence of high‐intensity interval training to exhaustion on the directional sensitivity of the cerebral pressure‐flow relationship in young endurance‐trained men

We previously reported subtle dynamic cerebral autoregulation (dCA) alterations following 6 weeks of high‐intensity interval training (HIIT) to exhaustion using transfer function analysis (TFA) on forced mean arterial pressure (MAP) oscillations in young endurance‐trained men. However, accumulating evidence suggests the cerebrovasculature better buffers cerebral blood flow changes when MAP acutely increases compared to when MAP acutely decreases. Whether HIIT affects the directional sensitivity of the cerebral pressure‐flow relationship in these athletes is unknown. In 18 endurance‐trained men (age: 27 ± 6 years, VO2max: 55.5 ± 4.7 ml·kg−1·min−1), we evaluated the impact of 6 weeks of HIIT to exhaustion on dCA directionality using induced MAP oscillations during 5‐min 0.05 and 0.10 Hz repeated squat‐stands. We calculated time‐adjusted changes in middle cerebral artery mean blood velocity (MCAv) per change in MAP (ΔMCAvT/ΔMAPT) for each squat transition. Then, we compared averaged ΔMCAvT/ΔMAPT during MAP increases and decreases. Before HIIT, ΔMCAvT/ΔMAPT was comparable between MAP increases and decreases during 0.05 Hz repeated squat‐stands (p = 0.518). During 0.10 Hz repeated squat‐stands, ΔMCAvT/ΔMAPT was lower during MAP increases versus decreases (0.87 ± 0.17 vs. 0.99 ± 0.23 cm·s−1·mmHg−1, p = 0.030). Following HIIT, ΔMCAvT/ΔMAPT was superior during MAP increases over decreases during 0.05 Hz repeated squat‐stands (0.97 ± 0.38 vs. 0.77 ± 0.35 cm·s−1·mmHg−1, p = 0.002). During 0.10 Hz repeated squat‐stands, dCA directional sensitivity disappeared (p = 0.359). These results suggest the potential for HIIT to influence the directional sensitivity of the cerebral pressure‐flow relationship in young endurance‐trained men.

Menstrual cycle and oral contraceptives influence cerebrovascular dynamics during hypercapnia.

Women experience fluctuating orthostatic intolerance during the menstrual cycle, suggesting sex hormones may influence cerebral blood flow. Young (aged 18–30) healthy women, either taking oral contraceptives (OC; n = 14) or not taking OC (NOC; n = 12), were administered hypercapnic gas (5%) for 5 min in the low hormone (LH; placebo pill) and high hormone (HH; active pill) menstrual phases. Hemodynamic and cerebrovascular variables were continuously measured. Cerebral blood velocity changes were monitored using transcranial doppler ultrasound of the middle cerebral artery to determine cerebrovascular reactivity. Cerebral autoregulation was assessed using steady‐state analysis (static cerebral autoregulation) and transfer function analysis (dynamic cerebral autoregulation; dCA). In response to hypercapnia, menstrual phase did not influence static cardiovascular or cerebrovascular responses (all p > 0.07); however, OC users had a greater increase of mean middle cerebral artery blood velocity compared to NOC (NOC‐LH 12 ± 6 cm/s vs. NOC‐HH 16 ± 9 cm/s; OC‐LH 18 ± 5 cm/s vs. OC‐HH 17 ± 11 cm/s; p = 0.048). In all women, hypercapnia improved high frequency (HF) and very low frequency (VLF) cerebral autoregulation (decreased nGain; p = 0.002 and <0.001, respectively), whereas low frequency (LF) Phase decreased in NOC‐HH (p = 0.001) and OC‐LH (p = 0.004). Therefore, endogenous sex hormones reduce LF dCA during hypercapnia in the HH menstrual phase. In contrast, pharmaceutical sex hormones (OC use) have no acute influence (HH menstrual phase) yet elicit a chronic attenuation of LF dCA (LH menstrual phase) during hypercapnia.

Middle cerebral artery blood flow stability in response to high-definition transcranial electrical stimulation: A randomized sham-controlled clinical trial

Since neuronal activity is coupled with neurovascular activity, we aimed to analyze the cerebral blood flow hemodynamics during and following high-definition transcranial direct current stimulation (HD-tDCS). We assessed the mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally using transcranial doppler ultrasound, during and after HD-tDCS, in eleven right-handed healthy adult participants (6 women, 5 men; mean age 31 ± 5.6 years old), with no evidence of brain or cardiovascular dysfunction. The HD-tDCS electrode montage was centered over the right temporo-parietal junction. The stimulation protocol comprised 3 blocks of 2 min at each current intensity (1, 2, and 3 mA) and an inter-stimulus interval of 5 min between blocks. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) on three different days, with an interval of at least 24 h. Stimulation was well tolerated across HD-tDCS conditions tested, and the volunteers reported no significant discomfort related to stimulation. There was no significant difference in the right or the left MCA-BFv during or after the stimulation protocol across all stimulation conditions. We conclude that at a range of intensities, vascular reaction assessed using middle cerebral artery blood flow is not significantly altered during or after HD-tDCS both locally and remotely, which provides further evidence for the safety of HD-tDCS.

Acute Impact of JUUL Electronic Cigarette use on Cerebral Vascular Vasodilator Responsiveness

BackgroundCardiovascular disease is a major cause of death among cigarette smokers and is responsible for ~30% of heart disease related mortality in the U.S each year. Although cigarette smoking rates have declined in recent years, the use of electronic cigarettes (e‐cigarettes) continues to gain popularity in the U.S. and have generated widespread debate within the public health community, mostly due to the lack of scientific evidence regarding their safety and impact on health and behavior. The increasing rates of e‐cigarette use in the U.S have been largely attributed to the recent emergence of the high‐nicotine‐delivery pod‐based devices such as JUUL. Unlike e‐cigarettes, the literature surrounding the health impact of combustible cigarette smoking is well developed with overwhelming evidence of an adverse impact on various cardiovascular outcomes including impaired cerebral perfusion/vascular function. However, the impact of e‐cigarettes on cerebral vascular function remains to be elucidated, representing a major knowledge gap and research priority.HypothesisThis study tested the hypothesis that acute e‐cigarette vaping (JUUL) will impair cerebral vascular function as indexed by the cerebral vasodilatory responsiveness to a hypercapnic stimulus.MethodsA total of 16 adult smokers (mean age=25±5 yrs.) participated in this pilot study which occurred following an overnight fast. Cerebral vascular function was assessed as the hyperemic response to rebreathing‐induced hypercapnia before and ~45 min following a vaping session (10 puffs; 3s each, separated by 30s intervals). Heart rate (ECG), respiration (Pneumotrace), beat‐to‐beat blood pressure (Finometer), middle cerebral artery mean blood velocity (MCAv ‐ transcranial Doppler) and breath‐by‐breath end‐tidal carbon dioxide concentration (PETCO2‐ capnograph) were continuously measured. Cerebral vascular conductance index (CVCi) was calculated as MCAv / mean arterial pressure. Cerebral vasodilatory responsiveness was assessed as % increase in CVCi (%CVCi) during the highest common magnitude of hypercapnia achieved during the pre‐ and post‐vaping trials.ResultsAll CVCi data are reported at the highest common magnitude of hypercapnia achieved during the pre‐ and post‐vaping sessions (ΔPETCO2Pre: 13±2 mmHg, ΔPETCO2 Post: 12±2 mmHg; P=0.11). Cerebral vascular function/vasodilatory responsiveness, as assessed by the CVCi response to the hypercapnic challenge was significantly blunted following the vaping session (Pre: +52±25%, Post: +42±14%; P=0.04).ConclusionsOur preliminary results suggest that e‐cigarette vaping using JUUL acutely impairs cerebral vascular function as indexed by cerebral vasodilatory responsiveness to a hypercapnic challenge. These findings highlight the need for longitudinal studies to assess the long‐term impact of JUUL use on cerebral vascular function as well as other indices of cardiovascular health.

Cerebral haemodynamics during arrhythmia in health, ischaemic heart disease and heart failure with reduced ejection fraction, and in a preclinical swine model.

Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n=11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n=9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n=11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA). Middle cerebral artery mean blood velocity (MCAVmean ) decreased during premature ventricular contraction (PVC) in all groups, and data from swine indicate PVCs reduced cerebral microvascular perfusion. Overall MCAVmean was decreased in the HFrEF vs. control group. Further, %∆MCAVmean /%∆mean arterial pressure during the PVC was greater in the HFrEF vs. control group and was correlated with decreased MoCA scores. Subanalysis of HFrEF data revealed that during bigeminy MCAVmean decreased owing to reductions during irregular beats only. During non-sustained ventricular tachycardia, MCAVmean decreased but recovered above baseline upon return to sinus rhythm. Also, haemodynamic perturbations during and following the PVC were greater in the brachial artery vs. the MCA. Therefore, ventricular arrhythmias decreased indices of cerebral perfusion irrespective of IHD or HFrEF. The relative magnitude of arrhythmia-induced haemodynamic perturbations appears to be population specific and arrhythmia type and organ dependent. The cumulative burden of arrhythmia-induced deficits may exacerbate existing cerebral hypoperfusion in HFrEF and contribute to neurological abnormalities in this population. KEY POINTS: Irregular heartbeats are often considered benign in isolation, but individuals who experience them frequently have a higher prevalence of cerebrovascular and/or cognitive associated disorders. How irregular heartbeats affect blood pressure and cerebral haemodynamics in healthy and cardiovascular disease patients, those with and without reduced ejection fraction, remains unknown. Here it was found that in the absence of symptoms associated with irregular heartbeats, such as dizziness or hypotension, single, multiple non-sustained and sustained irregular heartbeats influence cerebral haemodynamics in a population-specific, arrhythmia-type and organ-dependent manner. Relative deficits in the index of cerebral blood flow normalized to relative deficits in blood pressure were greatest in patients with heart failure with reduced ejection and inversely related with cognitive performance. Chronic arrhythmias may exacerbate existing cerebral hypoperfusion in heart failure with reduced ejection fraction, thereby providing a mechanistic link between otherwise benign irregular heartbeats and cognitive dysfunction, independent of embolism.

Hypercapnia elicits differential vascular and blood flow responses in the cerebral circulation and active skeletal muscles in exercising humans.

The purpose of this study was to investigate the effects of a rise in arterial carbon dioxide pressure (PaCO2) on vascular and blood flow responses in the cerebral circulation and active skeletal muscles during dynamic exercise in humans. Thirteen healthy young adults (three women) participated in hypercapnia and normocapnia trials. In both trials, participants performed a two‐legged dynamic knee extension exercise at a constant workload that increased heart rate to roughly 100 beats min−1. In the hypercapnia trial, participants performed the exercise with spontaneous breathing while end‐tidal carbon dioxide pressure (PETCO2), an index of PaCO2, was held at 60 mmHg by inhaling hypercapnic gas (O2: 20.3 ± 0.1%; CO2: 6.0 ± 0.5%). In the normocapnia trial, minute ventilation during exercise was matched to the value in the hypercapnia trial by performing voluntary hyperventilation with PETCO2 clamped at baseline level (i.e., 40–45 mmHg) through inhalation of mildly hypercapnic gas (O2: 20.6 ± 0.1%; CO2: 2.7 ± 1.0%). Middle cerebral artery mean blood velocity and the cerebral vascular conductance index were higher in the hypercapnia trial than in the normocapnia trial. By contrast, vascular conductance in the exercising leg was lower in the hypercapnia trial than in the normocapnia trial. Blood flow to the exercising leg did not differ between the two trials. These results demonstrate that hypercapnia‐induced vasomotion in active skeletal muscles is opposite to that in the cerebral circulation. These differential vascular responses may cause a preferential rise in cerebral blood flow.

Directional sensitivity of the cerebral pressure-flow relationship in young healthy individuals trained in endurance and resistance exercise.

What is the central question of this study? Does habitual exercise modality affect the directionality of the cerebral pressure-flow relationship? What is the main finding and its importance? These data suggest the hysteresis-like pattern of dynamic cerebral autoregulation appears present in long-term sedentary and endurance-trained individuals, but absent in resistance-trained individuals. This is the first study to expand knowledge on the directional sensitivity of the cerebral pressure-flow relationship to trained populations. Evidence suggests the cerebrovasculature may be more efficient at dampening cerebral blood flow (CBF) variations when mean arterial pressure (MAP) transiently increases, compared to when it decreases. Despite divergent MAP and CBF responses to acute endurance and resistance training, the long-term impact of habitual exercise modality on the directionality of dynamic cerebral autoregulation (dCA) is currently unknown. Thirty-six young healthy participants (sedentary (n=12), endurance-trained (n=12), and resistance-trained (n=12)) undertook a 5-min repeated squat-stand protocol at two forced MAP oscillation frequencies (0.05 and 0.10Hz). Middle cerebral artery mean blood velocity (MCAv) and MAP were continuously monitored. We calculated absolute (ΔMCAvT /ΔMAPT ) and relative (%MCAvT /%MAPT ) changes in MCAv and MAP with respect to the transition time intervals of both variables to compute a time-adjusted ratio in each MAP direction, averaged over the 5-min repeated squat-stand protocols. At 0.10Hz repeated squat-stands, ΔMCAvT /ΔMAPT and %MCAvT /%MAPT were lower when MAP increased compared with when MAP decreased for sedentary (ΔMCAvT /ΔMAPT : P=0.032; %MCAvT /%MAPT : P=0.040) and endurance-trained individuals (ΔMCAvT /ΔMAPT : P=0.012; %MCAvT /%MAPT P=0.007), but not in the resistance-trained individuals (ΔMCAvT /ΔMAPT : P=0.512; %MCAvT /%MAPT P=0.666). At 0.05Hz repeated squat-stands, time-adjusted ratios were similar for all groups (all P>0.605). These findings suggest exercise training modality does influence the directionality of the cerebral pressure-flow relationship and support the presence of a hysteresis-like pattern during 0.10Hz repeated squat-stands in sedentary and endurance-trained participants, but not in resistance-trained individuals. In future studies, assessment of elite endurance and resistance training habits may further elucidate modality-dependent discrepancies on directional dCA measurements.

Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex.

Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO2) is an important mechanism that maintains CO2 or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) responses to acute hypercapnia (5% CO2) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

Dynamic Cerebral Autoregulation following the Acute Consumption of Soft‐drinks in Healthy Adults

Chronic consumption of high-fructose corn syrup (HFCS) and artificially sweetened beverages (ASB) are associated with an increased risk of stroke. An attenuation in dynamic cerebral autoregulation (dCA), a measure cerebral vascular function during changes in arterial blood pressure, may indicate cerebral vascular dysfunction. Thus, understanding the acute effects that HFCS and ASB consumption has on dCA may help understand the increased risk of stroke associated with the chronic consumption of these beverages. Purpose We tested the hypothesis that dynamic cerebral autoregulation (dCA) is attenuated following the acute consumption of HFCS and ASB soft-drinks compared to Water. Methods Twelve healthy adults (age: 23±2 y, 4 females) completed three randomized, double-blind trials. Participants drank 500 mL of Water, HFCS (Mountain Dew) or ASB (Diet Mountain Dew). We continuously measured blood pressure (MAP), mean middle cerebral artery blood velocity (MCAv), and end-tidal CO2 tension (PETCO2). Cerebral vascular conductance (CVC) was calculated as mean MCAv/MAP. Twenty minutes after experimental beverage consumption participants completed a 5 minute seated baseline, followed by an oscillatory blood pressure challenge. The oscillatory blood pressure challenge consisted of squat-to-stand intervals at two different frequencies (0.10 Hz and 0.05 Hz) for 5 minutes each separated by 5 minutes of seated rest. dCA was assessed in the MCA using transfer function analysis. Coherence, gain and phase are reported in in predefined frequency domains: low frequency (LF; 0.07-0.2 Hz) and very low frequency (VLF; 0.01-0.07 Hz) for the 0.10 Hz and 0.05 Hz, respectively. Values are reported as mean±SD. Results At baseline, MCAv (HFCS: 53.7±11.5 and ASB: 52.2±10.3 vs. Water: 61.4±10.8 cm/s; p<0.01) and MCA CVC (HFCS: 0.6±0.2 and ASB: 0.5±0.1 vs. Water: 0.7±1 cm/s/mmHg; p<0.02) were lower following HFCS and ASB vs. Water. During the 0.10 Hz squat-to-stand, there were no differences between beverages for coherenceLF (p=0.30) or phaseLF (p=0.68). GainLF was lower following ASB (0.81±0.21 cm/s/mmHg) compared to Water (0.95±0.27 cm/s/mmHg; p=0.01) but there was no difference in gainLF between HFCS (0.92±0.23 cm/s/mmHg) and Water (p=0.53). During the 0.05 Hz squat-to-stand, there were no differences between beverages for coherenceVLF (p=0.83) or gainVLF (p=0.28). PhaseVLF was higher following ASB (45.4±8.5 degrees) compared to Water (39.8±8 degrees; p=0.06) but there was no difference in phaseVLF between HFCS (43.8±10.3 degrees) and Water (p=0.31). Conclusions Our data indicate that acute consumption of an ASB did not consistently alter dCA in both frequency bands. Additionally, dCA was not altered following a HFCS soft-drink. However, future research is warranted to determine the effects of chronic consumption of HFCS and ASB soft-drinks on cerebral vascular function and the increased the risk of stroke.

The middle cerebral artery blood velocity response to acute normobaric hypoxia occurs independently of changes in ventilation in humans

What is the central question of this study? Does the ventilatory response to moderate acute hypoxia increase cerebral perfusion independently of changes in arterial oxygen tension in humans? What is the main finding and its importance? The ventilatory response does not increase middle cerebral artery mean blood velocity during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation. Hypoxia induces ventilatory, cardiovascular and cerebrovascular adjustments to defend against reductions in systemic oxygen delivery. We aimed to determine whether the ventilatory response to moderate acute hypoxia increases cerebral perfusion independently of changes in arterial oxygenation. Eleven young healthy individuals were exposed to four 15min experimental conditions: (1) normoxia (partial pressure of end-tidal oxygen, =100mmHg), (2) hypoxia ( =50mmHg), (3) normoxia with breathing volitionally matched to levels observed during hypoxia (hyperpnoea; =100mmHg) and (4) hypoxia ( =50mmHg) with respiratory frequency and tidal volume volitionally matched to levels observed during normoxia (i.e., restricted breathing (RB)). Isocapnia was maintained in all conditions. Middle cerebral artery mean blood velocity (MCA Vmean ), assessed by transcranial Doppler ultrasound, was increased during hypoxia (58±12cm/s, P=0.04) and hypoxia + RB (61±14cm/s, P<0.001) compared to normoxia (55±11cm/s), while it was unchanged during hyperpnoea (52±13cm/s, P=0.08). MCA Vmean was not different between hypoxia and hypoxia + RB (P>0.05). These findings suggest that the hypoxic ventilatory response does not increase cerebral perfusion, indexed using MCA Vmean , during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation.