Cerebral Artery Blood Flow Velocity Research Articles

Cerebral autoregulation during exposure to artificial gravity

Our work has previously shown that exposure to artificial gravity (AG) can improve orthostatic tolerance. The purpose of this work is to examine whether cerebral autoregulation is improved with AG in twelve hypovolemic men and women. The protocol consisted of an initial ~45 minutes of a “step up” tolerance period, used to determine participants' presyncopal limit, followed by ~45 minutes training period at GZ below participants presyncopal limit. Beat‐by‐beat blood pressure (Portapres), heart rate (ECG), middle cerebral artery blood flow velocity (Transcranial Doppler) and end‐tidal carbon dioxide (capnography) were collected on participants during short arm centrifugation. Cerebral autoregulation was assessed using transfer function analysis between mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV) in 3‐min intervals during the training period. Exposure to AG resulted in a significant positive correlation between GZ and MAP, MAP variability and MCBFV variability in the low frequency (LF) range (0.07–0.15 Hz). In addition, coherence between MAP and MCBFV in the LF range was positively correlated. There was no change in gain and phase between MAP and MCBFV in the same frequency range. With higher GZ, there was a significant positive correlation in coherence and significant negative correlation in gain between MAP and MCBFV in the very low frequency range (0.03–0.07 Hz). These data suggest that increasing GZ exposure is correlated to increasing MAP variability. However, despite this increased MAP variability gain values demonstrated a negative correlation with GZ, suggesting that cerebral autoregulation tended to improve with increasing GZ exposure. We expect increased coherence was a result of the increased MAP variability associated with higher GZ. These data may suggest that exposure to AG may be helpful to improve cerebral autoregulation. Therefore, one could speculate that AG may be a useful tool to consider as a countermeasure for post‐flight astronauts to improve their orthostatic tolerance as well as cerebral autoregulation and improve re‐adaptation to a gravity environment.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cyclooxygenase Inhibition and Cerebrovascular Reactivity: Interaction of Aging and Aerobic Fitness

The ability of the cerebral microvessels to respond to chemical or metabolic stimuli declines with age and this change may be one mechanism through which age‐related cognitive decline occurs. Prostaglandins play an important role in the control of vascular tone, therefore changes in prostaglandin synthesis or expression may be underlying the age‐related alterations in cerebral microvascular function. Additionally, we have previously shown that aerobic fitness was associated with a decrease in cerebral microvascular function after cyclooxygenase (COX) blockade; yet this was in a small sample size of healthy older adults who were not exercise trained. Thus, the purpose of our study was to evaluate the effect of age on cerebral microvascular reactivity to hypercapnia (CVR) and to determine if habitual exercise modifies the response to COX blockade. We recruited 45 younger (YA; age = 26±1 y) and 31 older (OA; age = 63±1 y) healthy adults, including 21 sedentary YA, 24 exercising YA, 12 sedentary OA, and 19 exercising OA. Aerobic fitness (VO2 max) was measured during an incremental cycle ergometer test. Middle cerebral artery blood flow velocity (MCAv) and end‐tidal CO2 (ETCO2) were continuously recorded. CVR was calculated as the linear slope of the relationship between ETCO2 and MCAv and was assessed before and after the administration of the COX inhibitor indomethacin (INDO). The change in CVR was calculated as pre INDO CVR – post INDO CVR. There were no group differences in MCAv pre INDO (YA: 65±3 cm/s vs. OA: 59±3 cm/s; p>0.05); however, YA had higher MCAv post INDO (YA: 45±1 cm/s vs. OA: 40±2 cm/s; p<0.05). OA had significantly greater change in CVR compared with YA (2.0±0.1 cm/s/mmHg vs. 1.5±0.2 cm/s/mmHg, respectively; p<0.05). There was also a significant effect of habitual exercise, such that sedentary adults had a greater change in CVR compared with exercising adults (2.0±0.2 cm/s/mmHg vs. 1.5±0.2 cm/s/mmHg, respectively; p<0.05). In addition, there was an inverse association between VO2 max and the change in CVR in OA (r=0.42, p<0.05), but not in YA (p>0.05). Our results indicate that older adults, regardless of exercise status, rely more on COX‐derived products for cerebral microvascular responses to hypercapnia. Our results also suggest that habitual exercise may alter the contribution of COX‐derived products to cerebral blood flow regulation.Support or Funding InformationSupported by National Institute of Health grant HL118154This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Countdown before voluntary exercise induces muscle vasodilation with decreased muscle sympathetic nerve activity in humans

We examined whether countdown (CD) before voluntary bicycle ergometer exercise induced cerebro‐cardiovascular responses and, if so, whether these responses to CD were altered by postural change from the semi‐recumbent to supine position. Young men (n=14) performed voluntary cycle exercise in the semi‐recumbent position while middle cerebral artery blood flow velocity (CBF; Doppler ultrasonography), heart rate (HR), blood pressure (finger photoplethysmography), oxygen consumption rate (VO2), oxygen saturation in the right thigh muscle (StO2; near‐infrared spectrometry), cardiac output (CO; cZ method) and total peripheral resistance (TPR) were measured. The subjects repeated 8 trials, intermitted by more than 5‐min rest. In 4 trials randomly selected from 8 trials, the onset of exercise was signaled by a 30‐sec CD, whereas in the remaining 4 trials, exercise was started without CD. We found that CD increased CBF, HR, CO, mean blood pressure, and VO2 sequentially, decreasing TPR with increased StO2. To assess efferent signals causing vasodilation and the effects of posture change from the semi‐recumbent to supine position, other groups of subjects underwent the same exercise protocol but using only right leg in the semi‐recumbent (n=10) or supine (n=8) positions while muscle sympathetic nerve activity (MSNA; microneurography) and StO2 were measured in the left and right leg, respectively. We found that CD decreased MSNA burst frequency and total MSNA (both, P<0.05), which were significantly correlated with the increase in StO2 (both, P<0.001). However, these responses to CD were nearly abolished by the postural change. Thus, CD before starting voluntary exercise induced cerebro‐cardiovascular responses from central system to effector organs in a sequential manner in the semi‐recumbent position, but these responses were minimized while in the supine position.Support or Funding InformationThis study was supported by grants from the Japan Society for the Promotion of Science (24689014 and 15H04680).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Dynamic Cerebral Autoregulation Impairment Persists Past Resolution of Symptoms in Collegiate Athletes Following Concussion

ObjectivesDespite 3.8 million concussions occurring annually in the United States, the pathophysiological sequelae of the injury are still poorly understood. Animal and human studies have consistently reported deficits in cerebral blood flow (CBF) following concussion suggesting impairments in CBF regulation. Reductions in CBF are also associated with functional outcomes. The purpose of the study was to examine dynamic cerebral autoregulation (dCA) in an ongoing prospective cohort of collegiate athletes 3 days, 21 days, and 90 days following a concussion and compare them with non‐injured controls.Materials and MethodsTwenty‐seven NCAA and recreational athletes (20±1 years) with a physician diagnosed sports‐related concussions were enrolled in the study. For the injured athletes, data was collected on days 3,21, and 90 following concussion. Twenty‐five age and sports matched non‐injured controls (20±1 years) were also enrolled. For non‐injured controls, data was collected at one time point. Symptom number and severity was measured using the Sports Concussion Assessment Tool (SCAT‐3). Depression scores were assessed with Patient Health Questionnaire‐9 (PHQ‐9). Continuous mean arterial blood pressure (MBP) was obtained with finger photoplethysmography and middle cerebral artery blood flow velocity (MCAV) was obtained with a 2 MHz transcranial Doppler ultrasonography while subjects were seated in an upright position. dCA was estimated from transfer function (Tf) analysis of beat‐to‐beat spontaneous fluctuations in MBP and MCAV within the low (LF, 0.07–0.20 Hz) and high (HF, 0.20–0.35 Hz) frequency ranges. Effective dCA would attenuate spontaneous changes in MCAV in response to variations in MBP, which would correspond to relatively low transfer function gain. Independent and paired t‐tests were used to compare dCA between days 3, 21, and 90 following concussion with the non‐injured controls.ResultsCompare to the controls, concussed athletes exhibited greater symptom number on day‐3 (12.2±6.8 vs. 2.4±3.4; p<0.001) and higher PHQ‐9 score (8.7±5.6 vs. 2.1±2.1; p<0.001). LF Tf gain was higher on day‐3 (1.26±0.34U vs. 1.04±0.28U; p=0.016) compared to the controls. LF Tf gain continued to be high on day‐21 (1.30±0.45U; p=0.025) compared to the non‐injured controls despite no differences in symptoms number or depression scores between the groups. LF Tf gain was comparable to the controls on day‐90.ConclusionsDynamic cerebral autoregulation appears to be impaired at least up to 21 days following concussion despite improvement in symptom and depression. Cerebral autoregulation estimated from transcranial Doppler ultrasonography may be useful as a potential vascular biomarker for return‐to‐play decisions following a concussion preventing the risk of second‐impact syndrome.Support or Funding InformationThis work was supported by SMU University Research Council Grant, Spring 2015 & Texas Institute for Brain Injury and Repair (TIBIR) Pilot Grant 2016.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Whole blood viscosity and cerebral blood flow velocities in obese hypertensive or obese normotensive adolescents.

Obesity affects all major organ systems and leads to increased morbidity and mortality. Whole blood viscosity is an important independent regulator of cerebral blood flow. The aim of the present study was to evaluate the effect of whole blood viscosity on cerebral artery blood flow velocities using transcranial Doppler ultrasound in pediatric patients with obesity compared to healthy controls and analyze the effect of whole blood viscosity and blood pressure status to the cerebral artery blood flow velocities. Sixty patients with obesity diagnosed according to their body mass index (BMI) percentiles aged 13-18 years old were prospectively enrolled. They were grouped as hypertensive or normotensive according to their ambulatory blood pressure monitoring. Whole blood viscosity and middle cerebral artery velocities by transcranial Doppler ultrasound were studied and compared to 20 healthy same aged controls. Whole blood viscosity values in hypertensive (0.0619±0.0077 poise) and normotensive (0.0607±0.0071 poise) groups were higher than controls (0.0616±0.0064 poise), with no significance. Middle cerebral artery blood flow velocities were higher in the obese hypertensive (73.9±15.0 cm/s) and obese normotensive groups (75.2±13.5 cm/s) than controls (66.4±11.5 cm/s), but with no statistical significance. Physiological changes in blood viscosity and changes in blood pressure did not seem to have any direct effect on cerebral blood flow velocities, the reason might be that the cerebral circulation is capable of adaptively modulating itself to changes to maintain a uniform cerebral blood flow.

Compression garments and cerebral blood flow: Influence on cognitive and exercise performance

This study aimed to describe the effect of compression garments on middle cerebral artery blood flow velocity (MCAv) in relation to cognitive and exercise performance whilst cycling. In a randomised-controlled-cross-over design, 15 well-trained male cyclists were recruited to participate in three identical trials wearing loose fitting shorts (control), low-grade, or medium-grade compression garments. The protocol involved four 8 min increments of cycling at 30%, 50%, 70%, and 85% maximal power output and a 4 km time-trial. Participants undertook a cognitive Stroop task at baseline and at the midpoint of each increment. MCAv was monitored with Transcranial Doppler Ultrasonography. Mean arterial pressure (MAP) and partial pressure of end-tidal CO2 (PetCO2) were measured throughout. MCAv, MAP, PetCO2, and reaction time of the complex Stroop task were influenced by exercise intensity, but not compression garments. Compression garments significantly affected cognitive accuracy in the complex Stroop task such that low-grade compression appeared to enhance cognitive accuracy in comparison to the control condition at the highest intensity (p = .010). Time-trial performance did not differ between the control (338.0 ± 17.3 s), low-grade (338.7 ± 18.7 s), or medium-grade (342.2 ± 19.3 s) conditions (p = .114). Compression garments did not affect MCAv during exercise or time-trial performance, but compression may be beneficial for improved cognitive accuracy during high-intensity exercise. Further research is required to elucidate the potential impact on cognitive performance.

Intravenous saline administration in patients with severe acquired brain injury and orthostatic intolerance for tilt-table mobilization

ABSTRACTPrimary objective: This study aimed to investigate the effect of intravenous saline administration on orthostatic hypotension (OH) during head up tilt (HUT) and the change in the renin–angiotensin–aldosterone system before and after HUT in patients with severe acquired brain injury (ABI).Research design: The study is designed as an observational study.Methods and procedures: Fourteen patients with ABI, low level of consciousness and OH were monitored before, during and after HUT with non-invasive beat-to-beat blood pressure measurement, and transcranial Doppler determination of middle cerebral artery blood flow velocity. Blood samples were collected before and after two HUT sessions separated by 1 hour and saline was administered in between.Main outcomes and results: Patients’ ability to stand upright did not change after saline administration due to OH. The patients showed signs of reduced cerebral autoregulation at both HUT sessions. The patients had a significant lower level of renin and angiotensin II but not aldosterone.Conclusions: Patients with severe ABI and OH demonstrate no improvement in standing time with reduced plasma renin and angiotensin II after two HUT sessions and 1 hour fluid administration. Research focusing on the ability to retain fluid after bed rest is warranted.

Assessment of maternal cerebral blood flow velocity by transcranial Doppler ultrasound before delivery and in the early postpartum period

Objective: This prospective observational study aimed to identify the effects of labor on cerebral hemodynamics by measuring the middle cerebral artery (MCA) blood flow velocity by transcranial Doppler ultrasound (TCD), and the related factors just before delivery and within the 24 h after delivery. Methods: The study included 35 healthy pregnant women with a gestational age of >37 weeks who were in labor and a control group including healthy, age-matched, nonpregnant women (n = 24). Demographic characteristics and significant clinical information of pregnant women were recorded. The MCA blood flow velocity was assessed by TCD just before and within 24 h after delivery. The parameters assessed by TCD were mean cerebral blood flow velocity (MCBFV), peak systolic velocity (PSV), pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio. Results: There was no significant difference between the pregnant and nonpregnant women regarding age (27 ± 5 years versus 28 ± 7 years; p = .751). The MCBFV, PSV, PI, and RI showed a significant increase within the 24 h after delivery as compared with those before delivery. Comparison of the pregnant women with the control group in terms of the values of all parameters related to the MCA blood flow velocity revealed that the values that were significantly low before delivery reached to the level of the control group after delivery Conclusion: The findings of this study demonstrated that the blood flow velocity of the MCA decreased during the late pregnancy period and increased in the early postpartum period to the level similar to that of the nonpregnant group.

Hematoma volume is a predictive factor of disturbed autoregulation after spontaneous intracerebral hemorrhage

BackgroundDynamic cerebral autoregulation (dCA) is probably disturbed after spontaneous intracerebral hemorrhage (ICH) and could be an independent predictor of clinical outcome. Clinical determinants of dCA status after ICH need to be further elucidated. MethodsWe finally enrolled 53 patients diagnosed with supratentorial ICH within 6days from onset. DCA was assessed 4–6days after ICH onset by monitoring middle cerebral artery blood flow velocities and simultaneous arterial blood pressure continuously, utilizing transcranial Doppler combined with a servo-controlled finger plethysmograph. Cerebral autoregulation was evaluated by phase difference (PD) in low frequency (0.06–0.12Hz) range derived from transfer function analysis. The previous clinical history was collected including hypertension, diabetes mellitus, prior stroke, smoking, heavy drinking history. Laboratory results during hospitalization were utilized for further risk factors screening, including fasting blood glucose, glycosylated hemoglobin A (1C), total cholesterol, low density lipoprotein cholesterol and homocysteine, etc. Computed tomography scans were performed to collect neuroimaging data, including hematoma location, volume and presence of intraventricular hemorrhage. Univariate and multivariate linear analyses were adopted to explore the relationship between clinical and laboratory variables and bilateral PD respectively. ResultsIn ICH patients, PD was lower (indicating disturbed autoregulation) both on the ipsilateral (37.53±17.78 degree, P<0.001) and contralateral (34.45±14.92 degree, P<0.001) side of hematoma compared with healthy controls (56.13±16.11 degree). Hematoma volume was independently associated with ipsilateral PD according to multivariate analysis (β=−0.383, P=0.024) after adjustment for clinical and laboratory factors. ConclusionsDCA is bilaterally disturbed after supratentorial ICH. Larger hematoma volume is likely to independently predict poorer cerebral autoregulation status ipsilateral to hematoma.

Blunted cerebrovascular response is associated with elevated beta-amyloid

The goal of this study was to explore the association of beta-amyloid accumulation and cerebrovascular response (CVR) in cognitively normal older adults. Beta-amyloid accumulation was characterized with [18F] Florbetapir positron emission tomography scans. CVR was calculated as middle cerebral artery blood flow velocity change from rest to moderate intensity exercise. We found that individuals with elevated beta-amyloid aggregation had a blunted CVR (n = 25, age 70.1 ± 4.8; 3.3 ± 3.7 cm/s) compared to non-elevated individuals (n = 45, age 72.0 ± 4.9; 7.2 ± 5.0 cm/s, p < 0.001). Further, greater beta-amyloid burden was linearly associated with less CVR across all participants (b = −11.7, p < 0.001). Greater CVR and less beta-amyloid burden were associated with processing speed (p < 0.05). This study is the first to show that CVR from rest to exercise is blunted across increased global beta-amyloid burden.

The Relationship between Cerebral Vasoreactivity and Post-Concussive Symptom Severity.

While pathophysiology underlying post-concussion symptom burden is unknown, data suggest that cerebrovascular dysfunction may be among the culprits. We sought to determine whether the degree of impairment in the ability of cerebrovasculature to buffer against changes in arterial gases (vasoreactivity) is associated with concussion symptoms. In 15 participants (19 ± 5 years, 1 week to 1 year post-injury) diagnosed with concussion, we assessed vasoreactivity from the slope of the linear relationship of beat-by-beat middle cerebral artery blood flow velocity (transcranial Doppler ultrasound) to end-tidal CO2 during progressive increases in end-tidal CO2 (air rebreathing). Symptom burden was assessed using the Post-Concussion Symptom Scale. Subsequently, we explored the relationship between vasoreactivity and the severity of post-concussion headache and cognitive difficulties by linear models. During rebreathing, CO2 increased from 32.6 ± 1.6 to 46.8 ± 1.8 mmHg and cerebrovascular conductance (i.e., flow velocity over pressure) increased from 0.48 ± 0.04 to 0.74 ± 0.06 cms-1 mmHg-1. There was a strong linear relationship between the increase in CO2 and in conductance (R2 = 0.81 ± 0.05; p < 0.05). On average, cerebral vasoreactivity was 0.018 ± 0.003 cm-1 s-1 mmHg CO2-1. Although vasoreactivity tended to be somewhat higher in the asymptotic participants (0.019 ± 0.003 vs. 0.015 ± 0.005 cm-1 s-1 mmHg CO2-1), this difference was not statistically significant (p = 0.48). Higher vasoreactivity was strongly associated with more severe headaches (R2 = 0.57; p < 0.01) and worse cognitive symptoms (R2 = 0.71; p < 0.01). Thus, cerebral vasoreactivity relates strongly to post-concussive headache and cognitive symptom burden. This has significant implications for understanding the pathophysiology underlying post-concussive symptom burden and for devising effective treatment options.

Cerebral Blood Flow Responses to Aquatic Treadmill Exercise.

Aquatic treadmills are used as a rehabilitation method for conditions such as spinal cord injury, osteoarthritis, and stroke, and can facilitate an earlier return to exercise training for athletes. However, their effect on cerebral blood flow (CBF) responses has not been examined. We tested the hypothesis that aquatic treadmill exercise would augment CBF and lower HR compared with land-based treadmill exercise. Eleven participants completed incremental exercise (crossover design) starting from walking pace (4 km·h, immersed to iliac crest [aquatic], 6 km·h [land]) and increasing 1 km·h every 2 min up to 10 km·h for aquatic (maximum belt speed) or 12 km·h for land. After this, participants completed two 2-min bouts of exercise immersed to midthigh and midchest at constant submaximal speed (aquatic), or were ramped to exhaustion (land; increased gradient 2° every min). Middle cerebral artery blood flow velocity (MCAv) and HR were measured throughout, and the initial 10 min of each protocol and responses at each immersion level were compared. Compared with land-based treadmill, MCAvmean increased more from baseline for aquatic exercise (21% vs 12%, P < 0.001), while being associated with lower overall HR (pooled difference, 11 bpm; P < 0.001). MCAvmean increased similarly during aquatic walking compared with land-based moderate intensity running (~10 cm·s, P = 0.56). Greater water immersion lowered HR (139 vs 178 bpm for midchest vs midthigh), whereas MCAvmean remained constant (P = 0.37). Findings illustrate the potential for aquatic treadmill exercise to enhance exercise-induced elevations in CBF and thus optimize shear stress-mediated adaptation of the cerebrovasculature.

Dynamic wheelchair seating positions impact cardiovascular function after spinal cord injury.

BackgroundInnovative wheelchairs allow individuals to change position easily for comfort and social situations. While these wheelchairs are beneficial in multiple ways, the effects of position changes on blood pressure might exacerbate hypotension and cerebral hypoperfusion, particularly in those with spinal cord injury (SCI) who can have injury to autonomic nerves that regulate cardiovascular control. Conversely, cardiovascular benefits may be obtained with lowered seating. Here we investigate the effect of moderate changes in wheelchair position on orthostatic cardiovascular and cerebrovascular reflex control.MethodsNineteen individuals with SCI and ten neurologically-intact controls were tested in supine and seated positions (neutral, lowered, and elevated) in the Elevation™ wheelchair. Participants with SCI were stratified into two groups by the severity of injury to cardiovascular autonomic pathways. Beat-to-beat blood pressure, heart rate and middle cerebral artery blood flow velocity (MCAv) were recorded non-invasively.ResultsSupine blood pressure and MCAv were reduced in individuals with lesions to autonomic pathways, and declined further with standard seating compared to those with preserved autonomic control. Movement to the elevated position triggered pronounced blood pressure and MCAv falls in those with autonomic lesions, with minimum values significantly reduced compared to the seated and lowered positions. The cumulative duration spent below supine blood pressure was greatest in this group. Lowered seating bolstered blood pressure in those with lesions to autonomic pathways.ConclusionsIntegrity of the autonomic nervous system is an important variable that affects cardiovascular responses to orthostatic stress and should be considered when individuals with SCI or autonomic dysfunction are selecting wheelchairs.SponsorshipThis work was supported in part by the Heart and Stroke Foundation of British Columbia and the Yukon (V.E.C).

Random squat/stand maneuvers: a novel approach for assessment of dynamic cerebral autoregulation?

Squat/stand maneuvers (SSM) have been used to assess dynamic cerebral autoregulation (dCA), but always at a fixed frequency (FF). This study aimed to assess the use of random-frequency (RF) SSMs as a stimulus for measuring dCA and determine the reproducibility of FF and RFSSMs. Twenty-nine healthy volunteers [19 male, mean age 23.0 (4.9) yr] completed the study; 11 returned for a repeat visit (median 45 days). Heart rate, beat-to-beat blood pressure, middle cerebral artery (MCA) blood flow velocity, end-tidal CO2, and angle of the squat movement were measured. Subjects underwent four recordings: 5 min sitting, 5 min standing, FFSSMs (0.05Hz), and RFSSMs. Subjects were asked to rate the degree of exertion experienced while performing these maneuvers. Twenty-nine subjects completed the protocol; nine data sets were deemed unsuitable for further analysis. Mean ARI of 6.21 (1.04) while standing was significantly greater than during the SSMs (P < 0.01), with mean (SD) ARI during the FF and RFSSMs being 5.16 (1.43) and 5.37 (1.21), respectively. However, no significant difference was found between the ARI estimates from the two SSMs (P = 0.856) or for each of the four recordings between the two visits (P = 0.645). RFSSMs were found to be significantly less tiring than FFSSMs (P < 0.01). In conclusion, RFSSMs are an effective and noninvasive method of assessing dCA. There is no difference in the ARI estimates in comparison with FFSSMs. Although FFSSMs have been well tolerated previously, RFSSMs are preferred by healthy subjects and thus may be better tolerated by a patient population in a clinical setting.NEW & NOTEWORTHY RFSSMs provided comparable estimates of autoregulatory indices to FFSSMs. Instead of point estimates at the driven frequency, RFSSMs generate a broader power spectrum of changes in arterial blood pressure and cerebral blood flow velocity, allowing direct comparison with spontaneous fluctuations through transfer function analysis. Moreover, random-frequency SSMs are preferred by participants. They are a novel tool by which larger blood pressure oscillations can be elicited for the reliable measurement of dynamic cerebral autoregulation.

Influence of sex, menstrual cycle, and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing.

Women experience orthostatic intolerance more than men, and they experience faintness more in the early follicular [i.e., low-hormone (LH)] than luteal [i.e., high-hormone (HH)] phase of the menstrual cycle. Men (n = 13, 25.8 ± 1.8 yr old) and women in the LH (days 2-5; placebo) and HH (days 18-24; high dose) phases of the menstrual cycle with (OC; n = 14, 22.0 ± 0.8 yr old) or without (NOC; n = 12, 21.8 ± 0.5 yr old) oral contraceptive (OC) use underwent the Valsalva maneuver and a supine-sit-stand protocol. Blood pressure, normalized stroke volume [stroke volume index (SVi)], cardiac output index, heart rate, end-tidal CO2, and middle cerebral artery (MCA) blood flow velocity were measured. When subjected to the Valsalva maneuver, all women had a greater increase in diastolic and mean MCA blood flow velocity than men (P ≤ 0.065), with no significant effect of menstrual cycle phase or OC use. When subjected to the supine-sit-stand protocol, men had lower MCA blood flow velocity (P < 0.038) than all women, and SVi was higher in men than in the NOC group in all postures (P < 0.011) and in the OC group in the LH phase of the menstrual cycle during standing (P = 0.010). Only men experienced higher resistance index (P < 0.001) and pulsatility index (P < 0.001) with standing. The OC group had lower end-tidal CO2 (P = 0.002) than the NOC group (P = 0.030) and men (P ≤ 0.067). SVi (P = 0.004) and cardiac output index (P = 0.008) were higher in the OC than NOC group. A tendency toward a lower mean MCA blood flow velocity (P = 0.058) and higher SVi (P = 0.059) and pulsatility index (P = 0.058) was noted in the HH than LH phase. Mean arterial pressure was higher in the OC than NOC group in the LH phase (P = 0.049) and lower in the HH than LH phase (P = 0.014). Our results indicate that cycling estrogens/progestins can influence ventilatory, cardiovascular, and/or cerebrovascular physiology.NEW & NOTEWORTHY We have found sex differences in the cerebrovascular response to the Valsalva maneuver and standing. Men have greater cerebral vasoconstriction (or women have greater cerebral vasodilation) during late phase II of the Valsalva maneuver, and the cerebrovascular resistance index increases in men, but not in women, during standing. Furthermore, our findings indicate that both the menstrual cycle phase and oral contraceptive use can influence cardiovascular function both at rest and during active standing.

Middle cerebral artery blood flow velocity during a 4km cycling time trial.

This study sought to describe middle cerebral artery blood flow velocity (MCAv) during a 4km cycling time trial, and relate it to different pacing strategies adopted by participants. After familiarisation and a standardised exercise protocol, 15 male trained cyclists rode a 4km time trial on a cycling ergometer. MCAv was assessed via transcranial Doppler ultrasound in the right hemisphere at resting baseline, and throughout the time trial. Mean arterial pressure, end-tidal partial pressure of carbon dioxide (PetCO2) and heart rate were assessed alongside MCAv. Plasma lactate was assessed post time trial. Data were compared depending upon whether participants completed the time trial with a positive (first half faster than the last) or negative pacing profile although there was no difference in the time to completion with either pacing strategy (positive 344±23s, negative 334±14s; p=0.394). Lower mean MCAv (positive pacing -7.6±14.2%, negative pacing +21.2±15.0% compared to resting baseline measures; p=0.004) and lower PetCO2 (significant interaction p<0.001) towards the end of the time trial were observed with positive compared to negative pacing. Heart rate and lactate did not differ between pacing strategies. Changes in MCAv appear to depend on the pacing strategy adopted, with a positive pacing strategy likely to contribute to a hyperventilatory drop in PetCO2 and subsequent reduction in MCAv. Although lower cerebral blood flow cannot be directly linked to an inability to raise or maintain power output during the closing stages of the time trial, this potential contributor to fatigue is worth further investigation.

Dynamics of middle cerebral artery blood flow velocity during moderate-intensity exercise.

The dynamic response to a stimulus such as exercise can reveal valuable insights into systems control in health and disease that are not evident from the steady-state perturbation. However, the dynamic response profile and kinetics of cerebrovascular function have not been determined to date. We tested the hypotheses that bilateral middle cerebral artery blood flow mean velocity (MCAV) increases exponentially following the onset of moderate-intensity exercise in 10 healthy young subjects. The MCAV response profiles were well fit to a delay (TD) + exponential (time constant, τ) model with substantial agreement for baseline [left (L): 69, right (R): 64 cm/s, coefficient of variation (CV) 11%], response amplitude (L: 16, R: 13 cm/s, CV 23%), TD (L: 54, R: 52 s, CV 9%), τ (L: 30, R: 30 s, CV 22%), and mean response time (MRT) (L: 83, R: 82 s, CV 8%) between left and right MCAV as supported by the high correlations (e.g., MRT r = 0.82, P < 0.05) and low CVs. Test-retest reliability was high with CVs for the baseline, amplitude, and MRT of 3, 14, and 12%, respectively. These responses contrasted markedly with those of three healthy older subjects in whom the MCAV baseline and exercise response amplitude were far lower and the kinetics slowed. A single older stroke patient showed baseline ipsilateral MCAV that was lower still and devoid of any exercise response whatsoever. We conclude that kinetics analysis of MCAV during exercise has significant potential to unveil novel aspects of cerebrovascular function in health and disease.NEW & NOTEWORTHY Resolution of the dynamic stimulus-response profile provides a greater understanding of the underlying the physiological control processes than steady-state measurements alone. We report a novel method of measuring cerebrovascular blood velocity (MCAv) kinetics under ecologically valid conditions from rest to moderate-intensity exercise. This technique reveals that brain blood flow increases exponentially following the onset of exercise with 1) a strong bilateral coherence in young healthy individuals, and 2) a potential for unique age- and disease-specific profiles.

Effects of hypertonic sodium chloride hydroxyethyl starch solution on cerebral vasospasm in patients with ruptured aneurysm undergoing interventional embolization surgery

Objective To investigate the protective effect and potential mechanisms of hypertonic sodium chloride hydroxyethyl starch solution(HSH) on cerebral vasospasm (CVS) in patients with ruptured aneurysm undergoing interventional embolization surgery. Methods Thirty aSAH patients with Ⅱ or Ⅲ level of ASA and Hunt/Hess, 1 or 2 grade of improvement Fisher, 13-15 score of GCS, 18-80 years of age and undergoing interventional embolization surgery were randomly divided into 2 groups(n=15): group H and group N. For group H, patients received 4.2% HSH(4 ml/kg). For group N, patients received normal saline (4 ml/kg). Than, the MAP, CVP, plasma osmotic pressure(POP), HR, Na+, K+, Cl- were recorded at 8 AM of different day time points: preoperative induction (T0), the end of intravenous infusion of HSH or normal saline(T1), the end of surgery(T2), 1st day after operation(T3), 2nd day after operation(T4), 3rd day after operation(T5), 4th day after operation(T6), 5th day after operation(T7). Right middle cerebral artery blood flow velocity was monitored with transcranial doppler(TCD) at T3-T7. The plasma IL-6, TNF-α, endothelin-1(ET-1) andnitric oxide(NO) productions were measured by ELlSA, and glasgow coma scale(GCS), china stroke scale(CSS) and 24 h of fluid therapy were recorded at T3-T7. Results Compared with group N, CVP in group H was significantly higher than that in group N at T1-T7(P 0.05). Conclusions Intravenous infusion of HSH could effectively attenuate cerebral vasospasm in patients with aSAH undergoing interventional embolization surgery, which may be through inhibiting inflammation and breaking the imbalance of ET-1 and NO. Key words: Hypertonic sodium chloride hydroxyethyl starch solution; Intracranial aneurysms; Interventional therapy; Vasospasm

Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise.

We examined whether a change in posterior cerebral artery flow velocity (PCAv) reflected the posterior cerebral blood flow in healthy subjects during both static and dynamic exercise. PCAv and vertebral artery (VA) blood flow, as an index of posterior cerebral blood flow, were continuously measured during an exercise trial using transcranial Doppler (TCD) ultrasonography and Doppler ultrasound, respectively. Static handgrip exercise significantly increased both PCAv and VA blood flow. Increasing intensity of dynamic exercise further increased VA blood flow from moderate exercise, while PCAv decreased to almost resting level. During both static and dynamic exercise, the PCA cerebrovascular conductance (CVC) index significantly decreased from rest (static and high-intensity dynamic exercise, -11.5 ± 12.2% and -18.0 ± 16.8%, means ± SD, respectively) despite no change in the CVC of VA. These results indicate that vasoconstriction occurred at PCA but not VA during exercise-induced hypertension. This discrepancy in vascular response to exercise between PCA and VA may be due to different cerebral arterial characteristics. Therefore, to determine the effect of exercise on posterior cerebral circulation, at least, we need to carefully consider which cerebral artery to measure, regardless of exercise mode.NEW & NOTEWORTHY We examined whether transcranial Doppler-determined flow velocity in the posterior cerebral artery can be used as an index of cerebral blood flow during exercise. However, the changes in posterior cerebral artery flow velocity during exercise do not reflect vertebral artery blood flow.

Oscillatory lower body negative pressure impairs working memory task-related functional hyperemia in healthy volunteers.

Neurovascular coupling (NVC) describes the link between an increase in task-related neural activity and increased cerebral blood flow denoted "functional hyperemia." We previously showed induced cerebral blood flow oscillations suppressed functional hyperemia; conversely functional hyperemia also suppressed cerebral blood flow oscillations. We used lower body negative pressure (OLBNP) oscillations to force oscillations in middle cerebral artery cerebral blood flow velocity (CBFv). Here, we used N-back testing, an intellectual memory challenge as a neural activation task, to test the hypothesis that OLBNP-induced oscillatory cerebral blood flow can reduce functional hyperemia and NVC produced by a working memory task and can interfere with working memory. We used OLBNP (-30 mmHg) at 0.03, 0.05, and 0.10 Hz and measured spectral power of CBFv at all frequencies. Neither OLBNP nor N-back, alone or combined, affected hemodynamic parameters. 2-Back power and OLBNP individually were compared with 2-back power during OLBNP. 2-Back alone produced a narrow band increase in oscillatory arterial pressure (OAP) and oscillatory cerebral blood flow power centered at 0.0083 Hz. Functional hyperemia in response to 2-back was reduced to near baseline and 2-back memory performance was decreased by 0.03-, 0.05-, and 0.10-Hz OLBNP. OLBNP alone produced increased oscillatory power at frequencies of oscillation not suppressed by added 2-back. However, 2-back preceding OLBNP suppressed OLBNP power. OLBNP-driven oscillatory CBFv blunts NVC and memory performance, while memory task reciprocally interfered with forced CBFv oscillations. This shows that induced cerebral blood flow oscillations suppress functional hyperemia and functional hyperemia suppresses cerebral blood flow oscillations.NEW & NOTEWORTHY We show that induced cerebral blood flow oscillations suppress functional hyperemia produced by a working memory task as well as memory task performance. We conclude that oscillatory cerebral blood flow produces causal reductions of memory task neurovascular coupling and memory task performance. Reductions of functional hyperemia are constrained by autoregulation.