Middle Cerebral Artery Blood Flow Velocity Research Articles

SEX DIFFERENCES IN CEREBRAL BLOOD FLOW VELOCITY RESPONSES TO EXERCISE IN THE HEAT

INTRODUCTION & AIMS Global warming poses a risk for the development of heat-related physiological impairment, which can be aggravated when exercising in hot conditions. The aim of the present study was to investigate acute effects of exercising in hot conditions on cerebral blood flow velocity and systolic function in healthy individuals and to explore possible sex differences. METHODS The experimental condition consisted of walking on a treadmill, at 5km/h and 2% incline, inside a heat chamber at 40°C (50%RH), for 90 minutes. Middle cerebral artery blood flow velocity (MCAv) and left ventricular global longitudinal strain (GLS; a sensitive index of systolic function), were assessed at baseline and every 30 minutes by means of transcranial Doppler and speckle-tracking echocardiography, respectively. Data is expressed in delta (Δ) and standard error. RESULTS Twenty-six individuals (13♂,13♀ 27.1±1.0yrs, P=0.02) completed the experimental protocol. Both males and females exhibited non-significant increases in MCAv from baseline at 30 minutes (♂Δ=2.55±2.15 P>0.05; ♀Δ=0.54±2.53cm.s-1, P>0.05; interaction P=0.63), followed by significant decreases relative to 30min, at 60min (♂Δ=-4.0±1.23 P=0.04; ♀Δ=-5.41±1.56cm.s-1, P=0.03; interaction P=0.63) and 90 minutes (♂Δ=-6.08±1.37 P<0.01; ♀Δ=-7.39±1.40cm.s-1, P<0.01; interaction P=0.63). In males, there was a significant decrease in GLS from baseline at 30min (Δ=2.44±0.69%, P<0.05), 60 (Δ=2.79±0.73%, P=0.03), and 90 (Δ=3.49±0.89%, P=0.03) minutes; no significant changes were observed in females. CONCLUSION Males and females presented similar patterns of change in cerebral blood flow velocity, including significant decreases with prolonged heat exertion. These changes occur in both sexes, despite changes in systolic strain only being apparent in males. These data suggest that sex differences may exist in the regulation of cerebrovascular responses to exercise in the heat in humans.

The association between cerebral blood flow variations during on-pump coronary artery bypass grafting surgery and postoperative delirium.

Postoperative delirium (POD) has a major impact on patient recovery after cardiac surgery. Although its pathophysiology remains unclear, there could be a correlation between cerebral blood flow (CBF) variations during cardio-pulmonary bypass (CPB) and POD. Our study aimed to evaluate whether variations in on-pump CBF, compared to pre-anesthesia and pre-CPB values, are associated with POD following coronary artery bypass grafting (CABG) surgery. This prospective observational cohort study included 95 adult patients undergoing elective on-pump CABG surgery. Right middle cerebral artery blood flow velocity (MCAV) was assessed using Transcranial Doppler before anesthesia induction, before CPB and every fifteen minutes during CPB. Pre-anesthesia and pre-CPB values were chosen as baselines. Individual values, measured during CPB, were converted as percentage changes relative to these baselines and named as %MCAV0 and %MCAV1, respectively. POD was assessed using the Confusion Assessment Method for ICU (CAM-ICU) during the first 48 post-operative hours and with the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) on the fifth post-surgical day. Overall POD incidence was 17.9%. At 30minutes of CPB, %MCAV0 was higher in POD group than in no-POD group (p = .05). %MCAV0 at 45minutes of CPB was significantly higher in POD group (87 (±17) %) than in no-POD group (68 (±24) %), p = .04. %MCAV1 at 30 and 45minutes of CPB were higher in POD group than in no-POD group, at the limit of statistical significance. We found %MCAV1 > 100% in POD group, but not in no-POD group. Significant differences in %MCAV0 became evident after 30minutes of CPB, whereas differences in %MCAV1 at 45 minutes of CPB were at limit of statistical significance. In POD group %MCAV1 was higher than 100% at 30 and 45minutes of CPB, which is supposed to be a sign of cerebral hyperperfusion. Monitoring CBF during CPB could have prognostic value for POD.

Effects of butylphthalide on cerebral vascular circulation, coagulation function, and neurological function in patients with acute severe ischemic stroke following intravenous thrombolysis: a preliminary study

Objective To analyze the effects of Butylphthalide on cerebral vascular circulation, coagulation function, and neurological function in patients with acute severe ischemic stroke following intravenous thrombolysis. Methods Clinical efficacy, cerebral vascular circulation indicators [anterior cerebral artery (ACA), middle cerebral artery (MCA), vertebral artery (VA) blood flow velocity], coagulation function indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB)], neurological function indicators [Activities of Daily Living (ADL) score. Results The total effective rate of treatment in the control group was 76.47%, while in the observation group, it was 96.08%, with the observation group showing a significantly higher total effective rate than the control group (p < 0.05). Before treatment, there was no significant difference in ACA, MCA, and VA blood flow velocity between the two groups (p > 0.05). However, after treatment, the ACA, MCA, and VA blood flow velocity in the observation group were significantly higher than those in the control group (p < 0.05). Before treatment, there was no significant difference in PT, APTT, TT, and FIB levels between the two groups (p > 0.05). Conclusion In patients with acute severe ischemic stroke undergoing intravenous thrombolysis, the addition of Butylphthalide to the treatment regimen yields favorable clinical outcomes. Compared to Alteplase alone, the addition of Butylphthalide further improves cerebral vascular circulation and coagulation function, promoting the recovery and reconstruction of neurological function in patients. Importantly, the addition of Butylphthalide does not increase the risk of adverse reactions, making it a safe and ideal option for clinical application.

Comparison of diffuse correlation spectroscopy analytical models for measuring cerebral blood flow in adults.

Although multilayer analytical models have been proposed to enhance brain sensitivity of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow, the traditional homogeneous model remains dominant in clinical applications. Rigorous in vivo comparison of these analytical models is lacking. We compare the performance of different analytical models to estimate a cerebral blood flow index (CBFi) with DCS in adults. Resting-state data were obtained on a cohort of 20 adult patients with subarachnoid hemorrhage. Data at 1 and 2.5cm source-detector separations were analyzed with the homogenous, two-layer, and three-layer models to estimate scalp blood flow index and CBFi. The performance of each model was quantified via fitting convergence, fit stability, brain-to-scalp flow ratio (BSR), and correlation with transcranial Doppler ultrasound (TCD) measurements of cerebral blood flow velocity in the middle cerebral artery (MCA). The homogeneous model has the highest pass rate (100%), lowest coefficient of variation (CV) at rest (median [IQR] at 1Hz of 0.18 [0.13, 0.22]), and most significant correlation with MCA blood flow velocities (, ) compared with both the two- and three-layer models. The multilayer model pass rate was significantly correlated with extracerebral layer thicknesses. Discarding datasets with non-physiological BSRs increased the correlation between DCS measured CBFi and TCD measured MCA velocities for all models. We found that the homogeneous model has the highest pass rate, lowest CV at rest, and most significant correlation with MCA blood flow velocities. Results from the multilayer models should be taken with caution because they suffer from lower pass rates and higher coefficients of variation at rest and can converge to non-physiological values for CBFi. Future work is needed to validate these models in vivo, and novel approaches are merited to improve the performance of the multimodel models.

Effect of controlled blood pressure increase on cerebral blood flow velocity and oxygenation in patients with subarachnoid haemorrhage.

Patients with aneurysmal subarachnoid haemorrhage (SAH) might have impaired cerebral autoregulation, that is, CBF - and thereby oxygen delivery - passively increase with an increase in CPP. This physiological study aimed to investigate the cerebral haemodynamic effects of controlled blood pressure increase in the early phase after SAH before any signs of delayed cerebral ischaemia (DCI) occurred. The study was carried out within 5 days after ictus. Data were recorded at baseline and after 20 min of noradrenaline infusion to increase mean arterial blood pressure (MAP) by a maximum of 30 mmHg and to an absolute level of no more than 130 mmHg. The primary outcome was the difference in middle cerebral artery blood flow velocity (MCAv) measured by transcranial Doppler (TCD), while differences in intracranial pressure (ICP), brain tissue oxygen tension (PbtO2 ), and microdialysis markers of cerebral oxidative metabolism and cell injury were assessed as exploratory outcomes. Data were analysed using Wilcoxon signed-rank test with correction for multiplicity for the exploratory outcomes using the Benjamini-Hochberg correction. Thirty-six participants underwent the intervention 4 (median, IQR: 3-4.75) days after ictus. MAP was increased from 82 (IQR: 76-85) to 95 (IQR: 88-98) mmHg (p-value: <.001). MCAv remained stable (baseline, median 57, IQR: 46-70 cm/s; controlled blood pressure increase, median: 55, IQR: 48-71 cm/s; p-value: .054), whereas PbtO2 increased significantly (baseline, median: 24, 95%CI: 19-31 mmHg; controlled blood pressure increase, median: 27, 95%CI: 24-33 mmHg; p-value <.001). The remaining exploratory outcomes were unchanged. In this study of patients with SAH, MCAv was not significantly affected by a brief course of controlled blood pressure increase; despite this, PbtO2 increased. This suggests that autoregulation might not be impaired in these patients or other mechanisms could mediate the increase in brain oxygenation. Alternatively, a CBF increase did occur that, in turn, increased cerebral oxygenation, but was not detected by TCD. clinicaltrials.gov (NCT03987139; 14 June 2019).

Aortic stiffness and impairments in cerebrovascular function in cancer survivorship

An established consequence of anti-cancer treatment is increased aortic stiffness, which impairs the aortic damping of cardiac-generated pulsatile pressure and blood flow. These increased pulsations may result in vascular injury in the microcirculation of target end organs like the brain. The aim of the present study was to determine the ramifications of elevated aortic stiffness on cerebral macro- and microvascular pulsatility and autoregulatory function in cancer survivors. We hypothesized that cerebrovascular pulsatility would be enhanced, and cerebrovascular reactivity (CVR) to elevations in arterial CO 2 would be impaired, both in the large and small cerebral vessels in patients with a history of cancer and anti-cancer treatment versus healthy age- and sex-matched non-cancer controls. Aortic arch pulse wave velocity (aaPWV), a regional measure of stiffness in the proximal aorta, was calculated from echocardiographic views of the aortic valve and the descending aortic arch. Subjects then breathed room air for 60s followed by ~2 minutes of rebreathing with simultaneous collection of end-tidal pressure of CO 2 (P ET CO 2 ). Middle cerebral artery blood flow velocity (MCAv) was assessed using transcranial doppler. Oxygenated (oxy-[Hb]) and deoxygenated (deoxy-[Hb]) cerebral microvascular hemoglobin concentrations were monitored using two near-infrared spectroscopy probes placed over the prefrontal cortices. Pulsatility was assessed at baseline using Gosling’s Pulsatility Index (PI) for both the microvasculature and MCA. To account for changes in perfusion pressure, MAP was collected via finger plethysmography and cerebrovascular conductance indices were calculated for both oxy-[Hb] (CVCi oxy ) and MCAv (CVCi MCA ). CVR was calculated as the slope of CVCi oxy and CVCi MCA over P ET CO 2 during rebreathing. Six women were recruited (n = 3/group). Age was similar between the healthy non-cancer controls (HC) and patients with a history of cancer and anti-cancer treatment (CS) (31.0 ± 7 vs. 32.7 ± 13 years). Baseline ventilatory (P ET CO 2 ), central and cerebral hemodynamics were also similar (all p &gt; 0.05). aaPWV was significantly elevated in CS compared to HC (5.3 ± 0.6 vs. 3.1 ± 1.1 m/s, p = 0.04). Cerebral microcirculation PI in CS was significantly elevated (0.04 ± 0.01 vs. 0.02 ± 0.01, p = 0.02), but MCA PI was not different (p &gt; 0.05). CVR-CVCi oxy was impaired in CS (-3.6 ± 2.8 vs. 1.5 ± 0.5 nM·mmHg -1 /mmHg, p = 0.03), and CVR-CVCi MCA was similarly reduced (-0.05 ± 0.06 vs. 0.15 ± 0.01 mm/sec·mmHg -1 /mmHg, p &lt; 0.01). The increase in MAP during hypercapnia was similar between groups. Consistent with our hypothesis, both CVR-CVCi oxy and CVR-CVCi MCA were attenuated in patients with a history of anti-cancer treatment. Additionally, the microvascular pulsatility was greater in CS. This suggests an impaired cerebrovascular function, possibly related to increased transmission of pulsatility into the brain, in the years following cancer diagnoses and treatment. 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.

Middle cerebral artery dynamic cerebral autoregulation is impaired by infarctions in the anterior but not the posterior cerebral artery territory in patients with mild strokes.

The aim of this study was to ascertain whether dynamic cerebral autoregulation (CA) in the middle cerebral artery (MCA) is disturbed by cerebral infarctions outside the MCA territory. We estimated transfer function parameters gain and phase from simultaneous recordings of spontaneous oscillation in blood pressure and MCA cerebral blood flow velocity in 10 consecutive patients with isolated anterior cerebral artery (ACA) infarctions and in 22 consecutive patients with isolated posterior cerebral artery (PCA) infarctions. All ACA infarctions were in the motor, premotor, or supplementary motor cortex areas and presented with pronounced leg hemiparesis. Twenty-eight age- and sex-matched healthy subjects served as controls. Compared to controls, phase was significantly reduced in the MCA ipsilateral to the lesion site and in the contralateral MCA (unaffected hemisphere) in the very low (0.02-0.07 Hz) and low (0.07-0.15 Hz) frequency ranges in the ACA infarctions but not in the PCA infarctions. Gain was reduced only in the very low frequency range in the MCA contralateral to the ACA lesion site. Systemic factors were unrelated to phase and gain results. Bilateral impairment of MCA dynamic CA in patients with a unilateral ACA infarction is frequent.

Dantrolene Significantly Improves Cerebral Blood Flow in a Rat Model of Hemorrhagic Vasospasms

Introduction: A cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature and the primary cause of morbidity and mortality following a subarachnoid hemorrhage. The middle cerebral artery (MCA) is commonly affected by CVSPs. Concomitant administration of dantrolene and nimodipine synergistically reduces vasospasms in aortic rings from Sprague Dawley rats. To determine if the effects observed in the systemic vasculature extend to the cerebral circulation, we investigated the effect of intravenous administration of dantrolene (2.5 mg/kg) and nimodipine (1 mg/kg and 2 mg/kg) on MCA blood flow velocity (BFV) 7 days after the induction of CVSPs. Methods: Vasospasms were induced by bathing the left common carotid artery with autologous whole blood. Age-matched sham rats were used as controls. BFV, mean arterial pressure (MAP), and heart rate (HR) were measured with a PeriFlux 5000 Laser Doppler System, and a CODA non-invasive blood pressure system, before and after administering the drugs. Morphometric evaluations were also performed to assess vascular alterations. Results: BFV was reduced by 37% with dantrolene alone (n = 6, p ≤ 0.05) and by 27% with 2 mg/kg nimodipine (n = 6, p < 0.05), while it was not affected by 1 mg/kg nimodipine. The combination of 1 mg/kg nimodipine with dantrolene, however, decreased BFV by 35% (from 435.70 ± 21.53 to 284.30 ± 23.13 perfusion units, n = 7, p ≤ 0.05). A similar reduction (31%) was obtained with dantrolene and 2 mg/kg nimodipine (from 536.00 ± 32.61 to 367.80 ± 40.93 perfusion units, n = 6, p ≤ 0.05). Neither MAP nor HR was affected by dantrolene or nimodipine alone. The combination of dantrolene with 2 mg/kg nimodipine, however, decreased MAP and increased HR. Furthermore, 7 days after the induction of vasospasms, 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 finding suggests that vascular remodeling was present at this stage. Conclusion: Altogether, our results indicate that 2.5 mg/kg dantrolene significantly reduces BFV in the MCA without altering systemic hemodynamic parameters to a similar extent than the highest dose of nimodipine or the combination of dantrolene and the lowest dose of nimodipine. Therefore, dantrolene may provide a promising alternative to lower the risk, or partially revert, CVSP.

Clinical efficacy analysis of butylphthalide combined with urinary kallidinogenase in treating chronic cerebral circulatory insufficiency.

To investigate the clinical effect of butylphthalide combined with urinary kallidinogenase in the treatment of chronic cerebral circulatory insufficiency (CCCI). A total of 102 CCCI patients admitted to our hospital from October 2020 to December 2021 were retrospectively enrolled in this study. According to the different therapeutic strategy, the patients were divided into combined group (treated with butylphthalide combined with urinary kallidinogenase, n=51) and butylphthalide group (treated with butylphthalide, n=51). Blood flow velocity and cerebral blood flow perfusion before and after treatment between the two groups were compared. The clinical efficacy and adverse events of the two groups were analyzed. After treatment, the effective rate of the combined group was significantly higher than the butylphthalide group (p=.015). Before treatment, the blood flow velocity of middle cerebral artery (MCA), vertebral artery (VA), basilar artery (BA) were comparable (p>.05, respectively), while after treatment, the blood flow velocity of MCA, VA, and BA in combined group were faster than those in butylphthalide group (p<.001, respectively). Before treatment, the relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), relative mean transmit time (rMTT) of the two groups were comparable (p>.05, respectively). After treatment, rCBF and rCBV in combined group were higher than those in butylphthalide group (p<.001, respectively), and rMTT in combined group was lower than that in butylphthalide group (p=.001). The rate of adverse events in the two groups were comparable (p=.558). Butylphthalide combined with urinary kallidinogenase can improve the clinical symptoms of CCCI patients, and the effect is promising, which is worthy of clinical application.

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.

Fully Automated Transcranial Doppler Ultrasound for Middle Cerebral Artery Insonation

Background: Transcranial Doppler ultrasound (TCD) is utilized in the assessment of neurological conditions in clinical environments such as the intensive care unit and emergency department. However, obstacles for widespread use of TCD include a lack of trained registered vascular technologists (RVT) and operator variability. We present a study comparing RVT and a fully automated robotic TCD system (NovaGuide rTCD) for insonation of the middle cerebral artery (MCA).Methods: A trained RVT and rTCD sequentially collected bilateral MCA cerebral blood flow velocity (CBFV) from 86 healthy subjects. Mean CBFV (mCBFV) and the signal quality assessment (SQA) acquired manually by RVT and autonomously via rTCD were compared. Comparison metrics evaluated include mean accuracy ratio (MAR), and Bland-Altman mean-difference (MD) between rTCD and RVT with paired t-Test for significance. Bootstrapping was used in the accuracy ratio and mean-time to best signal computations to establish 95% confidence intervals.Results: The mCBFVs and SQAs found by rTCD compared to RVT had MAR of 99.7% (97.7-101.7%) and 102.7% (101.1-104.8%), respectively. The rTCD mean-time to best-quality signal was 0.87 min (0.71-1.05) (RVT was not timed). The mean-difference scores for mCBFV and SQA were MD=-0.43cm/s (&lt;i&gt;p&lt;/i&gt;=0.053) and MD=-0.36 (&lt;i&gt;p&lt;/i&gt;=0.61), respectively. The rTCD had a 3.5% no-window failure rate compared to RVT no-window rate of 4.1%.Conclusion: Comparison of bilateral TCD signals collected by rTCD and RVT demonstrated equivalence in mCBFV and signal quality, suggesting rTCD’s potential to expand utility of TCD in clinical settings that are resource-limited.

[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 Augmentation Effect Induced by External Counterpulsation Is Not Related to Impaired Dynamic Cerebral Autoregulation in Ischemic Stroke.

Background and PurposeDynamic cerebral autoregulation is impaired after ischemic stroke. External counterpulsation (ECP) augments the cerebral blood flow of patients with ischemic stroke by elevation of blood pressure (BP). We aimed to investigate if cerebral augmentation effects during ECP were associated with impaired dynamic cerebral autoregulation in patients after acute ischemic stroke.MethodsForty patients with unilateral ischemic stroke and large artery atherosclerosis in the anterior circulation territory within 7 days from symptom onset and eighteen healthy controls were recruited. We monitored changes in mean flow velocity over both middle cerebral arteries (MCA) by transcranial Doppler (TCD) before, during, and immediately after ECP. Cerebral augmentation index was MCA mean flow velocity increase in percentage during ECP compared with baseline to evaluate the augmentation effects of ECP. Spontaneous arterial BP and cerebral blood flow velocity in both bilateral MCAs were recorded using a servo-controlled plethysmograph and TCD, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), and gain.ResultsThe cerebral augmentation index in patients with stroke was significantly higher on both the ipsilateral and contralateral sides than that in controls, while the PD in patients with stroke was significantly lower on both sides than those in controls (all P < 0.05). The cerebral augmentation index did not correlate with PD and gain on either the ipsilateral or contralateral side of patients with stroke or in controls (all P > 0.05). The cerebral augmentation index of patients with stroke was significantly related to mean BP change on the ipsilateral side (R2 = 0.108, P = 0.038).ConclusionThe degree of ECP-induced cerebral augmentation effects as measured by the cerebral augmentation index did not correlate with the magnitude of impaired dynamic cerebral autoregulation.

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.

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.

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.

Cerebral Autoregulation Indices Are Not Interchangeable in Patients With Sepsis.

IntroductionDynamic cerebral autoregulation (dCA) is frequently altered in patients with sepsis and may be associated with sepsis-associated brain dysfunction. However, the optimal index to quantify dCA in patients with sepsis is currently unknown.ObjectiveTo assess the agreement between two validated dCA indices in patients with sepsis.MethodsRetrospective analysis of prospectively collected data in patients with sepsis; those with acute or chronic intracranial disease, arrhythmias, mechanical cardiac support, or history of supra-aortic vascular disease were excluded. Transcranial Doppler was performed on the right or left middle cerebral artery (MCA) with a 2-MHz probe, and MCA blood flow velocity (FV) and arterial pressure (BP) signals were simultaneously recorded. We calculated two indices of dCA: the mean flow index (Mxa), which is the Pearson correlation coefficient between BP and FV (MATLAB, MathWorks), and the autoregulation index (ARI), which is the transfer function analysis of spontaneous fluctuations in BP and FV (custom-written FORTRAN code). Impaired dCA was defined as Mxa >0.3 or ARI ≤ 4. The agreement between the two indices was assessed by Cohen's kappa coefficient.ResultsWe included 95 patients (age 64 ± 13 years old; male 74%); ARI was 4.38 [2.83–6.04] and Mxa was 0.32 [0.14–0.59], respectively. There was no correlation between ARI and Mxa (r = −0.08; p = 0.39). dCA was altered in 40 (42%) patients according to ARI and in 50 (53%) patients according to Mxa. ARI and Mxa were concordant in classifying 23 (24%) patients as having impaired dCA and 28 (29%) patients as having intact dCA. Cohen's kappa coefficient was 0.08, suggesting poor agreement. ARI was altered more frequently in patients on mechanical ventilation than others (27/52, 52% vs. 13/43, 30%, p = 0.04), whereas Mxa did not differ between those two groups. On the contrary, Mxa was altered more frequently in patients receiving sedatives than others (23/34, 68% vs. 27/61, 44%, p = 0.03), whereas ARI did not differ between these two groups.ConclusionsAgreement between ARI and Mxa in assessing dCA in patients with sepsis was poor. The identification of specific factors influencing the dCA analysis might lead to a better selection of the adequate cerebral autoregulation (CAR) index in critically ill patients with sepsis.

Effects of LI11 Acupuncture on CO2 reactivity in the anterior and middle cerebral arteries during hyperventilation-induced hypocapnia in normal subjects: A before and after study

Objectives: The LI11 (Quchi) acupuncture point has always been included in the Seven acupoints for stroke; however, additional LI11 acupuncture research is needed. In this study, the effect of LI11 acupuncture on cerebral blood flow of the anterior cerebral arteries (ACA) and middle cerebral arteries (MCA) was investigated.Method: This study included 10 healthy young male subjects. Cerebral blood flow velocity and cerebrovascular reactivity were measured using transcranial Doppler sonography. Changes in hyperventilation-induced carbon dioxide (CO2) reactivity and modified ACA and MCA blood flow velocity at 40 mmHg (CV40), blood pressure, and heart rate were observed before and after LI11 acupuncture treatment.Results: A statistically significant increase in contralateral anterior cerebral artery CO2 reactivity (p=0.036) and decrease in contralateral middle cerebral artery CV40 (p=0.047) were observed. No significant difference in mean blood pressure was shown. A statistically significant increase in heart rate occurred after LI11 acupuncture; however, it was not clinically significant as there were negligible changes in the heart rhythm.Conclusions: LI11 acupuncture treatment could improve cerebral blood flow velocity. These results might be explained by regulating endothelium-dependent vessel dilation in the anterior cerebral artery region.Trial registration: This trial has been registered with Clinical Research Information Service, a service of the Korea Centers for Disease Control and Prevention: KCT0004494 (retrospectively registered). https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=15359

Leptomeningeal collateral flow in patients with middle cerebral artery occlusion assessed by transcranial Doppler.

To explore the application value and clinical significance of transcranial Doppler(TCD)in assessing leptomeningeal collateral flow (LMF) status in patients with unilateral middle cerebral artery (MCA) occlusion. Medical records of patients with unilateral MCA occlusion confirmed by digital subtraction angiography (DSA) were analyzed retrospectively. The patients were divided into three groups according to LMF status, and the laboratory and imaging results were collected. Cerebral blood flow velocity (CBFV) of MCA, anterior cerebral artery (ACA), and posterior cerebral artery (PCA) on the affected side (ipsilateral, i) and the healthy side (contralateral, c) were measured and recorded by TCD. The results of CBFV changes detected by TCD were compared with those of DSA, and the correlation between CBFV changes and LMF status was analyzed. Eighty-four patients with unilateral MCA occlusion were included. CBFViACA and CBFViPCA were significantly faster than CBFVcACA and CBFVcPCA in patients with good LMF status (p<.05). There was a significant positive correlation between CBFViACA and LMF status (r = 0.697, p<.001). There was statistical significance in receiver operating characteristic curve analysis of CBFViACA and CBFViPCA (p<.05). The area under the curve of CBFViACA and CBFViPCA, respectively, was 0.879 and 0.678, and the best cutoff value was 82 and 60.5 cm/s. TCD can assess LMF status by detecting the changes of flow velocity of intracranial vessels. CBFV of ACA and PCA in patients with MCA occlusion is significantly correlated with LMF status by DSA. Assessing LMF status, CBFViACA, CBFViACA/CBFVcACA, and CBFViACA/CBFViMCA has the great diagnostic value, which is of great significance in guiding MCA occlusion patients to choose individualized treatment.