Middle Cerebral Artery Blood Flow Research Articles

Effects of Physical Exercise Training on Cerebral Blood Flow Measurements: A Systematic Review of Human Intervention Studies.

The aim of this systematic review was to examine the effects of physical exercise training on cerebral blood flow (CBF), which is a physiological marker of cerebrovascular function. Relationships between training-induced effects on CBF with changes in cognitive performance were also discussed. A systematic search was performed up to July 2022. Forty-five intervention studies with experimental, quasi-experimental, or pre-post designs were included. Sixteen studies (median duration: 14weeks) investigated effects of physical exercise training on CBF markers using magnetic resonance imaging, 20 studies (median duration: 14weeks) used transcranial Doppler ultrasound, and eight studies (median duration: 8weeks) used near-infrared spectroscopy. Studies using magnetic resonance imaging observed consistent increases in CBF in the anterior cingulate cortex and hippocampus, but not in whole-brain CBF. Effects on resting CBF-measured with transcranial Doppler ultrasound and near-infrared spectroscopy-were variable, while middle cerebral artery blood flow velocity increased in some studies following exercise or hypercapnic stimuli. Interestingly, concomitant changes in physical fitness and regional CBF were observed, while a relation between training-induced effects on CBF and cognitive performance was evident. In conclusion, exercise training improved cerebrovascular function because regional CBF was changed. Studies are however still needed to establish whether exercise-induced improvements in CBF are sustained over longer periods of time and underlie the observed beneficial effects on cognitive performance.

Measurement of resistance-area product by transcranial Doppler: An alternative tool for cognitive screening in hypertensive on drug treatment?

IntroductionArterial hypertrophy and remodeling are adaptive responses present in systemic arterial hypertension that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive performance (CP). However, CP is affected differently over time, so traditional screening methods may become less sensitive in assessing certain cognitive domains. The study aimed to evaluate whether cerebrovascular hemodynamic parameters can serve as a tool for cognitive screening in hypertensive without clinically manifest cognitive decline. MethodsParticipants were allocated into groups: non-hypertensive (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. Measurements of blood pressure and middle cerebral artery blood flow velocity were obtained from digital plethysmography and transcranial Doppler. For the cognitive assessment, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and a broad neuropsychological battery were applied. ResultsPatients in groups 2 and 3 show no significant differences in most of the clinical-epidemiological variables or pulsatility index (p = 0.361), however compared to group 1 and 2, patients in group 3 had greater resistance-area product [RAP] (1.7 [±0.7] vs. 1.2 [±0.2], p < 0.001). There was a negative correlation between RAP, episodic memory (r = -0.277, p = 0.004) and cognitive processing speed (r = -0.319, p = 0.001). ConclusionRAP reflects the real cerebrovascular resistance, regardless of the direct action of antihypertensive on the microcirculation, and seems to be a potential alternative tool for cognitive screening in hypertensive.

Amelioration of Brain Damage after Treatment with the Methanolic Extract of Glycyrrhizae Radix et Rhizoma in Mice.

Glycyrrhizae Radix et Rhizoma (GR) is a traditional herbal medicine widely used in Asian countries. GR was the most frequently used medicine among stroke patients in Donguibogam, the most representative book in Korean medicine. In the present study, we investigated the neuroprotective effects of the GR methanolic extract (GRex) on an ischemic stroke mice model. Ischemic stroke was induced by a 90 min transient middle cerebral artery occlusion (MCAO), and GRex was administered to mice with oral gavage after reperfusion of MCA blood flow. The MCAO-induced edema and infarction volume was measured, and behavioral changes were evaluated by a novel object recognition test (NORT). Immunofluorescence stains and Western blotting identified underlying mechanisms of the protective effects of GRex. GRex post-treatment in mice with MCAO showed potent effects in reducing cerebral edema and infarction at 125 mg/kg but no effects when the dosage was much lower or higher than 125 mg/kg. GRex inhibited the decrease of spontaneous motor activity and novel object recognition functions. The neuroprotective effects of GRex on ischemic stroke were due to its regulation of inflammation-related neuronal cells, such as microglia and astrocytes.

Evaluation of the changes in middle cerebral artery flow velocity related to different positions of patients during posterior fossa surgery.

This is a prospective observational study to evaluate the changes in middle cerebral artery flow velocities and cerebral perfusion pressure in the various positions used for posterior cranial fossa surgery and to correlate these changes with postoperative recovery characteristics and complications. Sixty patients were included in the study - 33 patients with CPA tumors were placed in the supine with head tilt position and the rest 27 with tumors in other locations of posterior fossa were placed in the prone position. The primary aim was to study the changes in middle cerebral artery blood flow velocity related to various positions of the patients used during posterior fossa surgery. The secondary aim was to compare the changes in pulsatility index, resistance index, and effective cerebral perfusion pressure in different position and to correlate these findings with postoperative recovery and the complications associated with these positions. The systolic and mean flow velocities were higher in the supine with head tilt group than the prone group after positioning and post repositioning, but these values were within normal limits, and the changes with positioning from baseline were comparable between the groups. Furthermore, these changes did not affect the effective cerebral perfusion pressure or the outcomes of the patients. The current results do not determine whether the supine with head tilt position is better than the prone position during posterior fossa surgery.

Association Between Cerebral Autoregulation and Long-Term Outcome in Patients With Acute Ischemic Stroke.

Dynamic cerebral autoregulation (CA) is known to be impaired in patients with acute ischemic stroke (AIS), but whether or not dynamic CA can predict long-term outcomes is unclear. This prospective study included 103 patients with AIS between September 2017 and April 2019. We measured the middle cerebral artery blood flow velocity and blood pressure within 7 days of AIS onset using a transcranial Doppler and Finometer, respectively. We conducted transfer function analysis to calculate dynamic CA indices (phase and gain), with lower phase and higher gain parameters reflecting less efficient CA. We followed up all patients after 3 and 12 months. Patients with 12-month modified Rankin Scale scores of <2 and ≥2 were defined as having favorable and unfavorable outcomes, respectively. We then analyzed the predictors of unfavorable outcomes after 3 and 12 months using logistic regression. The ipsilesional phase parameter was significantly lower in patients with unfavorable outcomes than in those with favorable outcomes. Multiple logistic regression analysis revealed that the ipsilesional phase parameter and the National Institutes of Health Stroke Scale score were nonmodifiable predictors of short-term and long-term outcomes. Moreover, in receiver operating characteristic analysis, the area under the curve of the ipsilesional phase parameter was 0.646 (95% confidence interval: 0.513-0.779, P =0.044). Notably, the optimal cut-off value was 20.33 degrees (sensitivity: 63%, specificity: 70%). Dynamic CA is an independent predictor of outcomes at 3 and 12 months in patients with AIS.

Clinical factors associated with cerebral autoregulation in ischemic stroke related to small artery occlusion

BackgroundExisting data suggest that cerebral autoregulation (CA) varies among different subtypes of ischaemic stroke. CA is globally impaired in patients with small artery occlusion (SAO). However, the factors influencing CA impairment in patients remains to be elucidated.MethodsStroke patients with SAO who underwent brain magnetic resonance imaging (MRI) were prospectively studied. Within 7 days after stroke onset, CA was recorded from the middle cerebral artery blood flow velocity and arterial blood pressure was simultaneously measured. Transfer function analysis was used to derive CA parameters, including gain and phase. Clinical characteristics, mean arterial pressure (MAP), biochemical findings, and cerebral small vessel disease (CSVD) markers on MRI were assessed in each patient. Factors associated with CA parameters were investigated. Univariate and multivariate linear regression analyses were conducted to determine the relationship between clinical factors and CA parameters.ResultsSixty-three SAO patients (age, 56.3 ± 9.9 years; 55 men) were enrolled in the study. In the multiple linear regression analysis, after controlling for relevant clinical factors, MAP on admission (ipsilateral OR = 0.99 and contralateral OR = 0.99, both P < 0.005) was a significant independent predictor of bilateral gain. MAP > 105 mmHg on admission (OR = 0.77, P = 0.019) was significantly associated with ipsilateral gain. Diabetes mellitus was a significant predictive factor for bilateral gain (ipsilateral OR = 1.32 and contralateral OR = 1.22, both P < 0.005). No correlations were found between CA parameters and CSVD characteristics.ConclusionIn SAO-related ischaemic stroke, patients with MAP > 105 mmHg on admission tended to have better ipsilateral CA. Diabetes mellitus appears to be an independent risk factor for CA impairment in patients with SAO-related stroke. CSVD may not be the main factor affecting bilateral CA in patients with SAO.

Post-reperfusion hyperperfusion after endovascular stroke treatment: a prospective comparative study of TCD versus MRI

BackgroundIncreased middle cerebral artery (MCA) blood flow velocities on transcranial duplex sonography (TCD) were recently reported in individual patients after successful mechanical thrombectomy (MT) and were related to intracranial hemorrhage...

Cardiovascular and cerebrovascular responses to urodynamics testing after spinal cord injury: The influence of autonomic injury.

Autonomic dysfunction is a prominent concern following spinal cord injury (SCI). In particular, autonomic dysreflexia (AD; paroxysmal hypertension and concurrent bradycardia in response to sensory stimuli below the level of injury) is common in autonomically-complete injuries at or above T6. AD is currently defined as a >20 mmHg increase in systolic arterial pressure (SAP) from baseline, without heart rate (HR) criteria. Urodynamics testing (UDS) is performed routinely after SCI to monitor urological sequelae, often provoking AD. We, therefore, aimed to assess the cardiovascular and cerebrovascular responses to UDS and their association with autonomic injury in individuals with chronic (>1 year) SCI. Following blood draw (plasma norepinephrine [NE]), continuous SAP, HR, and middle cerebral artery blood flow velocity (MCAv) were recorded at baseline (10-minute supine), during standard clinical UDS, and recovery (10-minute supine) (n = 22, age 41.1 ± 2 years, 15 male). Low frequency variability in systolic arterial pressure (LF SAP; a marker of sympathetic modulation of blood pressure) and cerebral resistance were determined. High-level injury (≥T6) with blunted/absent LF SAP (<1.0 mmHg2) and/or low plasma NE (<0.56 nmol•L−1) indicated autonomically-complete injury. Known electrocardiographic markers of atrial (p-wave duration variability) and ventricular arrhythmia (T-peak–T-end variability) were evaluated at baseline and during UDS. Nine participants were determined as autonomically-complete, yet 20 participants had increased SAP >20 mmHg during UDS. Qualitative autonomic assessment did not discriminate autonomic injury. Maximum SAP was higher in autonomically-complete injuries (207.1 ± 2.3 mmHg) than autonomically-incomplete injuries (165.9 ± 5.3 mmHg) during UDS (p < 0.001). HR during UDS was reduced compared to baseline (p = 0.056) and recovery (p = 0.048) only in autonomically-complete lesions. MCAv was not different between groups or phases (all p > 0.05). Cerebrovascular resistance index was increased during UDS in autonomically-complete injuries compared to baseline (p < 0.001) and recovery (p < 0.001) reflecting intact cerebral autoregulation. Risk for both atrial and ventricular arrhythmia increased during UDS compared to baseline (p < 0.05), particularly in autonomically-complete injuries (p < 0.05). UDS is recommended yearly in chronic SCI but is associated with profound AD and an increased risk of arrhythmia, highlighting the need for continued monitoring during UDS. Our data also highlight the need for HR criteria in the definition of AD and the need for quantitative consideration of autonomic function after SCI.

Statin contribution to middle cerebral artery blood flow velocity in older adults at risk for dementia.

It is plausible that statins could improve cerebral blood flow through pleiotropic mechanisms. The purpose of this investigation was to assess the contribution of statins to cerebrovascular variables in older adults with dyslipidemia and familial history of dementia. Furthermore, we explored the interaction between statin use and sex due to prevalent bias in statin trials. Middle cerebral artery blood flow velocity (MCAv) was measured using transcranial Doppler ultrasound. Continuous supine rest recordings lasted 8min. Participants included in analyses were statin (n = 100) or non-statin users (n = 112). MCAv and cerebrovascular conductance were significantly higher in statin users (p = 0.047; p = 0.04), and pulsatility index (PI) was significantly lower in statin users (p < 0.01). An interaction effect between statin use and sex was present for PI (p = 0.02); female statin users had significantly lower cerebrovascular resistance than the other three groups. In this cross-sectional analysis, statin use was positively associated with cerebrovascular variables in older adults at risk for dementia. Female statin users had significantly higher resting MCAv and cerebrovascular conductance than female non-statin users. The greatest contribution of statin use was the association with reduced cerebrovascular resistance. Given that cerebrovascular dysregulation is one of the earliest changes in Alzheimer's disease and related dementia pathology, targeting the cerebrovasculature with statins may be a promising prevention strategy.

Effect of a standardized maternal meal on fetal middle cerebral artery Doppler indices: A single-blinded crossover study.

ObjectiveMeasures of Doppler blood flow velocity profiles are an integral part of monitoring fetal well-being during pregnancy. These examinations are performed at different times of the day and at different maternal meal states. In uncomplicated pregnancies, we assessed the effect of a standardized maternal meal on middle cerebral artery (MCA) and umbilical artery (UA) Doppler blood flow velocity pulsatility indices (PIs) and MCA peak systolic velocity (PSV).MethodsIn this prospective single-blinded crossover study 25 healthy women were examined at 36 weeks of pregnancy. The first examination was performed in the morning following overnight fast, and repeated after extended fast (state A), and after a standard breakfast meal (state B).ResultsIrrespective of maternal prandial status, the MCA-PI values were lower in the 2nd compared to the 1st examination (-0.187; p = 0.071, and -0.113; p = 0.099, state A and B, respectively). Compared to the values in the 1st examination, the UA-PI values, were higher after extended fast (0.014; p = 0.436), and lower post-prandially (-0.036; p = 0.070). The difference (state B minus state A) between the meal states were not significant (0.074; p = 0.487 and -0.050; p = 0.058, for MCA-PI and UA-PI, respectively). Adjusting for the possible influence of fetal heart rate on MCA-PI and UA-PI, the differences between meal states remained non-significant (p = 0.179, p = 0.064, respectively). The MCA-PSV values increased after the meal (6.812; p = 0.035), whereas no increase was observed following extended fast (0.140; p = 0.951). The difference in MCA-PSV values between the two meal states was not significant (6.672; p = 0.055).ConclusionOur results demonstrate possible diurnal variations in MCA-PI and UA-PI, with and without adjustment for fetal heart rate, that seem to be unaffected by maternal meal intake in healthy pregnancies.

Cerebrovascular reactivity depending on rheumatoid factor and anticitrullinated protein antibody positivity in hypertensive patients with rheumatoid arthritis

Objective – to investigate cerebrovascular reactivity (CVR) depending on rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity in hypertensive patients with rheumatoid arthritis (RA).Subjects and methods. A single cross-sectional study included 61 patients (mean age 59.8±7.7 years; 6 men and 55 women) with combined RA and grade 1–2 hypertension (HTN). The duration of RA was 11.2±7.4 years. The duration of HTN was 12.1±8.6 years. All patients were treated with methotrexate. RA patients were categorized into RF/ACPA seronegative and RF/ACPA seropositive subgroups. CVR was evaluated by bilateral transcranial Doppler sonography of the middle cerebral arteries (MCA) in a hyperoxic test (O2 CVR) and in a hypercapnic test (CO2 CVR). We measured MCA mean blood flow velocity (Vmn), time average maximal blood flow velocity (TAMX), peak systolic velocity (Vps) at baseline, within 2 minutes of 100% oxygen inhalation and within 3 minutes of recovery phase (hyperoxic test). We calculated the following indicators for assessing CVR: index changes of flow velocity mean (IFVm), speed modification of velocity (SMFVm) and normalized answer of reserve (NAR). Then, according to the same scheme, we performed a hypercapnic test with the inhalation of a 4% mixture of carbon dioxide with air. Values are presented as Me [Q1 ; Q3 ].Results and discussion. Hypertensive patients with RA had a decrease in response power of MCA blood flow to hyperoxia. RF-seropositive RA patients had a more pronounced decrease in the power of the response to hyperoxia compared with RF-seronegative RA patients. The values of IFVm in the hyperoxic test were –13.4 [–19.9; –0.9] versus –16.2 [–22.7; –13.4]% (р=0.0453), respectively. ACPA-seropositive RA patients had not only a more pronounced decrease in the power of the response of MCA blood flow to hyperoxia, but also a more pronounced slowdown in the response velocity of MCA blood flow to hyperoxia compared with ACPA-seronegative RA patients. The values of IFVm in the hyperoxic test were –9.74 [–15.9; 2.84] versus –20.9 [–25.0; –14.7]% (р=0.0062), the values of SMFVm were –0.05 [–0.09; 0.02] versus –0.09 [–0.20; –0.05] sm/s2 (р=0.0488) respectively. Combined RA and HTN patients had a decrease in response power of MCA blood flow to hypercapnia. However, no statistical differences were found in the state of CO2 CVR between patients with seropositive RA and seronegative RA.Conclusion. Hypertensive patients with seropositive RA have a more pronounced O2 CVR disorder in compared to seronegative RA patients.

Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome.

Despite its increasing recognition and extensive research, there is no unifying hypothesis on the pathophysiology of the postural tachycardia syndrome. In this cross-sectional study, we examined the role of fear conditioning and its association with tachycardia and cerebral hypoperfusion on standing in 28 patients with postural tachycardia syndrome (31 ± 12 years old, 25 females) and 21 matched controls. We found that patients had higher somatic vigilance (P = 0.0167) and more anxiety (P < 0.0001). They also had a more pronounced anticipatory tachycardia right before assuming the upright position in a tilt-table test (P = 0.015), a physiological indicator of fear conditioning to orthostasis. While standing, patients had faster heart rate (P < 0.001), higher plasma catecholamine levels (P = 0.020), lower end-tidal CO2 (P = 0.005) and reduced middle cerebral artery blood flow velocity (P = 0.002). Multi-linear logistic regression modelling showed that both epinephrine secretion and excessive somatic vigilance predicted the magnitude of the tachycardia and the hyperventilation. These findings suggest that the postural tachycardia syndrome is a functional disorder in which standing may acquire a frightful quality, so that even when experienced alone it may elicit a fearful conditioned response. Heightened somatic anxiety is associated with and may predispose to a fear-conditioned hyperadrenergic state when standing. Our results have therapeutic implications.

Efficacy of nimodipine in the treatment of subarachnoid hemorrhage: a meta-analysis.

Subarachnoid hemorrhage (SAH) is an uncommon and serious subtype of stroke, which leads to the loss of the patient's ability to produce and live for many years. To investigate the clinical effect of nimodipine in the treatment of SAH. Electronic databases including China National Knowledge Infrastructure (CNKI), VIP, SinoMed, China Master's Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed and Embase were searched from 2010 and 2021. All randomized controlled trials evaluating the efficacy of nimodipine in the treatment of SAH were included in our meta-analysis. The patients were divided into control group and treatment group. Meta-analysis was performed with Stata16.0 software. A total of 10 studies were included. Compared with the control group, the treatment group had higher effective rate (OR = 3.21, 95% CI: 2.25, 4.58; p < 0.001), and lower incidence of adverse reactions (OR = 0.35, 95% CI: 0.19, 0.67; p = 0.001). Before treatment, no significant differences were identified in middle cerebral artery blood flow velocity and Glasgow coma scale (GCS) score between the two groups. However, after treatment, the middle cerebral artery blood flow velocity (SMD = -1.36, 95% CI: -2.28, -0.49; p = 0.002) and GCS score (SMD = 1.24, 95% CI: 0.58, 1.89; p < 0.001) in the treatment group were significantly better than those in the control group. Nimodipine is effective in the treatment of SAH, lowering incidence of adverse reactions and therefore improving the prognosis of patients.

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.

The 496th case:recurrent syncope for 8 years

A 25-year-old women was admitted to the department of Neurology in Affiliated 2nd Hospital of Hainan Medical University due to recurrent syncope for 8 years and return for 2 months. She had multiple episodes of syncope at onset. She presented with the feeling of weakness in both lower limbs, and fatigue in the past year. She experienced pain in the waist and limbs joint in recent three months. Physical examination showed joint hyperactivity in metacarpophalangeal joints of both upper limbs, increased skin elasticity. Active-standing transcranial Doppler (TCD) test showed that the average heart rate (HR) and the average middle cerebral artery (MCA) blood flow velocity in the supine position were 79 beats/min and 62 cm/s, respectively; while the average HR and the average MCA blood flow velocity in the standing position were 126 beats/min, 47 cm/s. Meanwhile,the blood pressure was normal during the test of supine-to-standing TCD. Genetic testing indicated LDB3 transgenation. The patient was diagnosed as postural tachycardia syndrome (joint-hypermobility-related), Ehlers-Danlos syndrome, and relieved by fluid infusion and rehabilitation therapy.

Physiological Mechanisms and Significance of Intracranial B Waves.

ObjectiveRecently published studies have described slow spontaneous cerebral blood flow (CBF) and cerebrospinal fluid (CSF) oscillations measured by magnetic resonance imaging (MRI) as potential drivers of brain glymphatic flow, with a similar frequency as intracranial B-waves. Aiming to establish the relationship between these waveforms, we performed additional analysis of frequency and waveform parameters, of our previously published transcranial Doppler (TCD) and intracranial pressure (ICP) recordings of intracranial B waves, to compare to published MRI frequency measurements of CBF and CSF slow oscillations.Patients and MethodsWe analyzed digital recordings of B waves in 29 patients with head injury, including middle cerebral artery (MCA) flow velocity (FV), ICP, end tidal CO2, and arterial blood pressure (ABP). A subset of these recordings demonstrated high B wave activity and was further analyzed for parameters including frequency, interaction, and waveform distribution curve features. These measures were compared to published similar measurements of spontaneous CBF and CSF fluctuations evaluated using MRI.ResultsIn patients with at least 10% amplitude B wave activity, the MCA blood flow velocity oscillations comprising the B waves, had a maximum amplitude at 0.0245 Hz, and time derivative a maximum amplitude at 0.035 Hz. The frequency range of the B waves was between 0.6–2.3 cycles per min (0.011-0.038 Hz), which is in the same range as MRI measured CBF slow oscillations, reported in human volunteers. Waveform asymmetry in MCA velocity and ICP cycles during B waves, was also similar to published MRI measured CBF slow oscillations. Cross-correlation analysis showed equivalent time derivatives of FV vs. ICP in B waves, compared to MRI measured CBF slow oscillations vs. CSF flow fluctuations.ConclusionsThe TCD and ICP recordings of intracranial B waves show a similar frequency range as CBF and CSF flow oscillations measured using MRI, and share other unique morphological wave features. These findings strongly suggest a common physiological mechanism underlying the two classes of phenomena. The slow blood flow and volume oscillations causing intracranial B waves appear to be part of a cascade that may provide a significant driving force for compartmentalized CSF movement and facilitate glymphatic flow.

Cerebral hemodynamics during sustained intraoperative hypotension.

Static cerebral autoregulation (CA) maintains cerebral blood flow (CBF) relatively constant above a mean arterial blood pressure (BPmean) of 60-65 mmHg. Below this lower limit of CA (LLCA), CBF declines along with BPmean. Data are lacking in describing how CA reacts to sustained hypotension since hypotension is usually avoided. In this study, we took advantage of a procedure requiring sustained hypotension. We assessed static CA for LLCA determination, and a more continuous CA, which counters short-term blood pressure variations. With these data, we analyzed CA during longstanding hypotension. Continuous arterial blood pressure and middle cerebral artery blood flow velocity (MCAVmean) were monitored in 23 patients that required deep intraoperative hypotension. The LLCA was determined for every patient, and BPmean below this LLCA was classified as the patient-specific hypotension. With the mean flow index (Mxa), continuous CA (Mxa-CA) was quantified. Mxa was calculated and averaged after induction of general anesthesia (baseline), every 15 min during, and 15 min after 1 h of hypotension. Functioning CA was defined as Mxa < 0.4. Data are expressed as median (25th-75th percentile). The LLCA was located at 56 (47-74) mmHg. At baseline, Mxa was 0.21 (0.14-0.32) and 0.61 (0.48-0.78) during hypotension (P < 0.01), with no appreciable change over time, n = 12. After blood pressure restoration, Mxa improved, 0.25 (0.06-0.35, n = 9). Mxa-CA became and remained disturbed during the 1 h of hypotension, and improved after blood pressure restoration. This completely reversible situation suggests no ischemic hyperemia occurs and renders an adaptation mechanism during sustained hypotension unlikely.NEW & NOTEWORTHY Intraoperative hypotension is normally avoided by anesthesiologists. However, for the Personalized External Aortic Root Support (PEARS) procedure, deep-induced hypotension is an essential requirement for the surgeon to be able to manipulate the aortic root. In this procedure, blood pressure and middle cerebral artery blood flow velocity were monitored. In this study, we assessed cerebral autoregulation during sustained hypotension, to give an insight into its behavior during hypotension.

The Influence of Sleep Duration on Cerebrovascular Reactivity

The impaired ability of the cerebrovasculature to dilate in response to a vasoactive stimulus (i.e., cerebrovascular reactivity, CVR) is associated with an increased risk of cognitive impairment. The association between sleep duration and dementia risk is “U‐shaped”, where adults who achieve seven hours of sleep have the lowest risk of cognitive impairment, compared to adults who achieve greater than or less than seven hours of sleep. In otherwise healthy adults, poor sleep quality and duration impairs peripheral vascular function, but its effect on CVR in generally healthy adults has remained largely been unexplored. The purpose of this study was to assess the relation between subjective sleep quality and CVR in healthy adults. Because the relation between sleep duration and cognitive impairment is an inverted U‐shape, we hypothesized that CVR would be lower in adults who slept longer than or shorter than the recommended 7‐8 hours of sleep. Data from thirty‐five individuals across the adult lifespan (21 males / 14 females, age: 44 ± 17 years; BMI: 26.8 ± 4.8 kg/m2; blood pressure, BP: 114 ± 12 / 71 ± 10 mmHg; heart rate, HR: 62 ± 8 bpm) were included in this analysis. CVR was assessed by measuring the change in middle cerebral artery blood flow velocity (MCAv) at baseline and following a 3‐minute hypercapnic stimulus (+9 mmHg increase in the end‐tidal partial pressure of CO2) using transcranial Doppler ultrasound. MCAv was normalized to beat‐to‐beat BP (MCACVC), and CVR was calculated as the percentage change in MCACVC and normalized to the absolute change in end‐tidal CO2.Sleep duration was negatively predictive of lower CVR (R2=0.17, β1± SE = ‐0.45 ± 0.18 %/mmHg/hour, P=0.014). A correlation matrix was performed to determine if any variables other than sleep duration (e.g., age, sex, etc) might also impact CVR. Age (P=0.53), BMI (P=0.93), systolic BP (P=0.22), diastolic BP (P=0.84), HR (P=0.071), and mean arterial pressure (P=0.57) were not associated with CVR. Only sex was significantly associated with CVR (R= ‐0.36, P=0.036), where men had augmented CVR compared to women (2.20 ± 0.73 %/mmHg vs. 1.59 ± 0.93 %/mmHg, P=0.036). Importantly, sex (β1± SE= ‐0.18 ± 0.27 %/mmHg, P=0.51) did not influence the relation between CVR (β1± SE= ‐0.41 ± 0.16 %/mmHg/hour, P=0.013) and sleep duration (model adjusted for sex: R2= 0.17, P=0.042). In conclusion, longer sleep duration was independently associated with lower CVR in healthy adults. Future studies should include more individuals with shorter sleep duration to test the possibility of an inverted U‐shaped association with CVR.

The Effects of Transcutaneous Vagal Nerve Stimulation on Dynamic Cerebral Autoregulation

PurposeTranscutaneous vagal nerve stimulation (tVNS) applied to the cervical branch of the vagus nerve is FDA‐approved to treat migraine and cluster headache. tVNS applied to the auricle branch of the vagus nerve (tVNSab) reduces muscle sympathetic nerve activity and improves cardiac parasympathetic activity after one session in healthy participants. Given the use of tVNS to treat cerebral disorders and its effects on autonomic function, we postulated that tVNSab might be beneficial for cerebral vascular function. We tested the hypotheses that tVNSab will increase resting middle cerebral artery blood flow velocity (MCAv) and improve dynamic cerebral autoregulation (dCA) during a repeated squat‐to‐stand procedure.MethodsSeven healthy participants (age: 20 ± 3 y; BMI:19 ± 7 kg/m2; 3 women) completed two randomized experimental visits on separate days. One visit consisted of tVNSab using a transcutaneous electrical nerve stimulation device (pulse width = 200 ms; pulse frequency = 30 Hz) with electrodes attached to the tragus of each ear. A time‐control visit (SHAM) was conducted with electrodes attached to the tragus but no current was applied. Mean arterial pressure (MAP; photoplethysmography), the partial pressure of end‐tidal carbon dioxide (PETCO2; capnography) and MCAv (transcranial Doppler ultrasound) were measured continuously. After 45 min of resting tVNS or SHAM, subjects performed a repeated squat‐to‐stand maneuver at a frequency of 0.05 Hz for 5 min while tVNSab or SHAM continued. Resting conductance values for the MCA (MCAc) were calculated as MCAv/MAP. MCA dCA was assessed during the squat‐to‐stand maneuver using spectral analyses to obtain coherence, gain, and phase values in the very low frequency (VLF) and low frequency (LF) bands. Spectral analysis gain was also assessed using normalized units (gainn), defined as beat to beat values divided by the mean value relative to changes in blood pressure. Data are presented as mean ± SD.ResultsThere were no differences between tVNSab and SHAM for MAP (tVNSab: 103 ± 8; SHAM: 102 ± 12 mmHg; P=0.41), PETCO2 (tVNSab: 35 ± 5; SHAM: 36 ± 2 mmHg; P=0.42), MCAv (tVNSab: 61.5 ± 9.2; SHAM: 58.7 ± 13.3 cm/s, P=0.36) or MCAc (tVNSab: 0.60 ± 0.08; SHAM: 0.59 ± 0.19 cm/s/mmHg, P=0.46) during baseline. There were no differences between conditions for coherence at VLF (tVNSab: 0.43 ± 0.14; SHAM: 0.45 ± 0.34; P=0.44) or LF (tVNSab: 0.65 ± 0.17; SHAM: 0.72 ± 0.13; P=0.06). Phase in the VLF (tVNSab: 0.35 ± 0.32; SHAM: 0.33 ± 0.36 rad; P=0.44) and LF (tVNSab: 0.28 ± 0.23; SHAM: 0.30 ± 0.16 rad; P=0.36) were not different. Gain (tVNSab: 0.56 ± 0.30; SHAM: 0.56 ± 0.54 cm/s/mmHg; P=0.50) and gainn (tVNSab: 0.99 ± 0.53; SHAM: 0.85 ± 0.84 %/mmHg; P=0.37) in the VLF were not different. However, gain (tVNSab: 0.76 ± 0.14; SHAM: 0.86 ± 0.17 cm/s/mmHg; P=0.02) and gainn (tVNSab: 1.22 ± 0.16; SHAM: 1.35 ± 0.23 %/mmHg; P=0.04) in the LF were lower during tVNSab.ConclusiontVNSab did not alter resting cerebral vascular responses. However, MCA LF gain was lower during tVNSab versus SHAM. These preliminary data indicate that dCA in a major intracranial cerebral artery might be improved during a single session of tVNSab. Further research regarding the influence of chronic tVNSab on cerebral vascular function is warranted.

Dantrolene Significantly Improves Cerebral Blood Flow In Diabetic Rats With Cerebral Vasospasms

Cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature, and the primary cause of morbidity and mortality following a hemorrhagic stroke. Diabetics have a greater predisposition for developing CVSPs than nondiabetics, even when under glycemic control. The middle cerebral artery (MCA) is one of the most common vessels affected by CVSPs. Experimental evidence shows that concomitant administration of dantrolene (a ryanodine receptor blocker) and nimodipine (a Ca+2 channel blocker) synergistically reduces vasospasms in aortic rings from streptozotocin (STZ)‐induced diabetic rats. To determine if the effects observed in the systemic vasculature extend to the cerebral circulation, we investigated the effects of intravenous administration of dantrolene (2.5 mg/kg) and nimodipine (1 mg/kg and 2 mg/kg) on MCA blood flow velocity (BFV) seven days after the induction of CVSP in diabetic rats. Vasospasms were induced by bathing the external surface of the left common carotid artery with autologous whole blood. BFV was measured with a PeriFlux 5000 Laser Doppler System before, and sixty minutes after administering the drugs. Morphometric evaluations of the common carotid arteries were also performed to assess vascular alterations secondary to the induction of vasospasms. BFV was reduced by 30% with dantrolene alone (from 495.90 ±21.38 to 345.50±31.46 perfusion units, n=6, p≤0.05), however, nimodipine alone (1mg/kg or 2 mg/kg) did not affect this variable. The combination of dantrolene with 1 mg/kg nimodipine decreased BFV by 22% (from 518.90±31.49 to 405.50±23.84 perfusion units, n=7, p≤0.05), while a 32% reduction was obtained with the combination of dantrolene and 2 mg/kg nimodipine (from 504.60±15.38 to 344.90±36.98 perfusion units, n=6, p≤0.05). Furthermore, seven days after the induction of vasospasms, the lumen area of the left common carotid artery decreased, whereas media thickness and the wall‐to‐lumen ratio increased when compared to contralateral controls. The latter findings suggest that a period of seven days after the induction of vasospasms, was sufficient to cause vascular remodeling. Thus, our results indicate that, in diabetic rats, 2.5 mg/kg dantrolene alone was as effective as the combination of dantrolene and the highest dose of nimodipine in reducing BFV in the MCA. Therefore, dantrolene may provide a promising alternative therapy for the treatment of CVSP in the diabetic population.