Increase In Cerebral Blood Flow Velocity Research Articles

The effect of head-down tilt in experimental acute ischemic stroke.

Collateral therapeutics exert a promising protective effect on the outcome of acute ischemic stroke. Cerebral blood flow (CBF) may be modulated by different head positioning. The current study aimed to determine the effect of head-down tilt (HDT) on stroke in a rodent model. The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was used in this study. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride staining, brain water content, perivascular aquaporin protein-4 (AQP4) localization, pericyte marker platelet-derived growth factor receptor β (PDGFRβ), and CBF velocity were evaluated at 24 h after MCAO/R and HDT treatment. In the rat model of MCAO/R, brain infarct volume and neurological deficit score were significantly alleviated in the -30° and -60° groups compared to those in the lying flat (0°) group. Compared with the 0° group, an increase in CBF velocity was detected in the -30° group through two-photon microscopy imaging at 24 h after MCAO/R. Compared with the SHAM group, a decrease in PDGFRβ was observed in both the MCAO/R and HDT treatment (-30°) groups. The integrated optical density of PDGFRβ was found to be higher in the HDT treatment (-30°) group than in the MCAO/R group. An impairment in perivascular AQP4 polarity and an increase in brain water content were observed after MCAO/R, which were not exacerbated by HDT treatment (-30°). Our findings suggest that HDT treatment at certain degrees may exert a neuroprotective effect after MCAO/R through improving CBF velocity and the protection of pericytes.

Short-Term Volume Loading Effects on Estimated Intracranial Pressure in Human Volunteers.

BACKGROUND: Short-term fluid loading is used as part of post-spaceflight medical procedures and clinical treatment in hospitals. Hypervolemia with hemodilution induced by rapid fluid infusion reportedly impaired dynamic cerebral autoregulation. However, the effects on intracranial pressure (ICP) remain unknown. Therefore, we estimated ICP noninvasively (nICP) to examine whether rapid fluid infusion would raise ICP.METHODS: Twelve healthy male volunteers underwent two discrete normal saline (NS) infusions (15 and 30 ml · kg-1 stages, NS-15 and NS-30, respectively) at a rate of 100 ml · min-1. The cerebral blood flow (CBF) velocity (CBFv) waveform from the middle cerebral artery obtained by transcranial Doppler ultrasonography was recorded, as was the arterial blood pressure (ABP) waveform at the radial artery obtained by tonometry. We then used these waveforms to calculate nICP, cerebral artery compliance, and the pulsatility index (PI) in an intracranial hydraulic model.RESULTS: nICP increased significantly in both infusion stages from preinfusion (preinfusion: 7.6 ± 3.4 mmHg; NS-15: 10.9 ± 3.3 mmHg; NS-30: 11.7 ± 4.2 mmHg). No significant changes were observed in cerebral artery compliance or PI. Although ABP did not change in any stage, CBFv increased significantly (preinfusion: 67 ± 10 cm · s-1; NS-15: 72 ± 12 cm · s-1; NS-30: 73 ± 12 cm · s-1).DISCUSSION: Hypervolemia with hemodilution induced by rapid fluid infusion caused increases in nICP and CBFv. No changes were observed in cerebral artery compliance or PI related to cerebrovascular impedance. These findings suggest that rapid fluid infusion may raise ICP with increased CBF.Kurazumi T, Ogawa Y, Takko C, Kato T, Konishi T, Iwasaki K. Short-term volume loading effects on estimated intracranial pressure in human volunteers. Aerosp Med Hum Perform. 2022; 93(4):347-353.

Neuroergonomics and Vigilance: Probing the Event-Related Cerebral Hemodynamic Response

Vigilance is an operator’s ability to sustain attentional focus and remain alert for a prolonged period of time in order to monitor for and detect critical task-relevant stimuli (Davies & Parasuram...

CEREBRAL HEMODYNAMIC CHANGES DURING MODERATE INTENSITY EXERCISE IN OLDER ADULTS WITH HIGH AND NORMAL RESTING PULSATILITY INDEX

A large body of recent evidence shows a substantial overlap exists among abnormality in the pulsatility index (PI) and cognitive decline. PI can be quantified using transcranial Doppler (TCD) measurement of cerebral blood flow velocities (CBFV) in the middle cerebral artery (MCA). PI of the MCA is postulated to reflect the vascular resistance in the arteries distal from the location of acoustic insonation. Higher PI indicates increased arterial rigidity and decreased arterial compliance and it is associated with a clinical diagnosis of Alzheimer disease. Physical exercise is suggested to have a beneficial effect on cognition in older adults. The study aimed to compare cerebral hemodynamic changes during exercise in older adults with normal and high resting PI. We enrolled eighty-one cognitively normal elderly subjects aged from 65 to 86 years old with a Clinical Dementia Rating (CDR) score of 0. TCD envelope, end-tidal carbon dioxide (PETCO2) and beat-to-beat mean arterial blood pressure (MAP) were recorded during moderate intensity exercise. The pulsatility index (PI) for each cardiac cycle during rest was calculated and averaged. The participants were divided into two groups based on the resting PI value: Fifty participants with normal resting PI, and thirty-one with high resting PI. The threshold for normal resting PI was age-adjusted using a formula adapted from the Rotterdam study 0.97 + (0.01*(Participant age - 65)). Percentage change from rest to exercise in TCD parameters, PETCO2, and MAP between the two groups were compared. Both groups showed a significant increase in mean CBFV, PETCO2, and MAP (P=0.01). Participants with normal resting PI showed a significant increase in PI during exercise. No change in PI during exercise was observed in those with high resting PI. This was mainly driven by a significant increase in diastolic velocity (Vd).

Cerebral Blood Flow during Interval and Continuous Exercise in Young and Old Men.

Aging is associated with impaired cerebral blood flow (CBF) and increased risk of cerebrovascular disease. Acute increases in CBF during exercise may initiate improvements in cerebrovascular health, but the CBF response is diminished during continuous exercise in older adults. The effect of interval exercise for promoting increases in CBF in young and old adults is unknown. We compared middle cerebral artery blood velocity (MCAv), end-tidal CO2 (PETCO2) and blood pressure (mean arterial pressure [MAP]) during intensity- and work-matched bouts of continuous (10-min 60%Wmax, followed by 10-min rest) and interval cycling (10 × 1-min 60%Wmax, separated by 1-min rest) in 11 young (25 ± 3 yr) and 10 old (69 ± 3 yr) men. Middle cerebral artery velocity was higher during continuous compared with interval exercise in the young (P < 0.001), but not in the old. This trend was also seen for changes in PETCO2. Although absolute MAP was higher in the old, the relative rise (%[INCREMENT]) in MAP was similar between age groups and was greater during continuous exercise than interval. When we assessed the total accumulated change in MCAv (area under curve: exercise + recovery), it was higher with interval compared with continuous exercise in both groups (P = 0.018). These findings suggest that interval exercise may be an effective alternative for promoting acute increases in CBF velocity, particularly in those older adults who may have difficulty sustaining continuous exercise.

Real-Time Cerebral Hemodynamic Response to Tactile Somatosensory Stimulation.

Recent studies in rodents suggest that somatosensory stimulation could provide neuroprotection during ischemic stroke by inducing plasticity in the cortex-vasculature relationship. While functional magnetic resonance imaging (fMRI) has shown that somatosensory stimulation increases cerebral blood flow (CBF) over several seconds, subsecond changes in CBF in the basal cerebral arteries have rarely been studied due to temporal resolution limitations. This study characterized hemodynamic changes in the middle cerebral arteries (MCAs) during somatosensory stimulation with high temporal resolution (100 samples/s) using functional transcranial Doppler ultrasound (fTCD). Pneumotactile somatosensory stimulation, consisting of punctate pressure pulses traversing the glabrous skin of the hand at 25 cm/s, was used to induce CBF velocity (CBFV) response curves. Changes in CBFV were measured in the bilateral MCAs using fTCD. All 12 subjects underwent three consecutive trials consisting of 20 seconds of stimulation followed by 5 minutes of rest. Sharp, bilateral increases in CBFV of about 20% (left MCA = 20.5%, right MCA = 18.8%) and sharp decreases in pulsatility index of about 8% were observed during stimulation. Left lateralization of up to 3.9% was also observed. The magnitude of the initial increase in CBFV showed significant adaptation between subsequent trials. Pneumotactile somatosensory stimulation is a potent stimulus that can evoke large, rapid hemodynamic changes, with adaptation between successive stimulus applications. Due to its high temporal resolution, fTCD is useful for identifying quickly evolving hemodynamic responses, and for correlating changes in hemodynamic parameters such as pulsatility index (PI) and CBFV.

The assessment of neurovascular coupling with the Addenbrooke's Cognitive Examination: a functional transcranial Doppler ultrasonographic study.

Cerebrovascular dysfunction occurs early in dementia and can be identified by transcranial Doppler ultrasonography (TCD). Few studies have examined cerebral blood flow velocity (CBFv) responses to a detailed cognitive battery. This study aimed to characterize all CBFv responses, and the effect of hemispheric dominance, to the Addenbrooke's Cognitive Examination (ACE-III) in healthy volunteers. Forty volunteers underwent continuous bilateral TCD, beat-to-beat blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO2 (ETCO2; capnography) monitoring. After a 5-min baseline period, all tasks from the ACE-III were performed in 3 sections (A: attention, fluency, memory; B: language; C: visuospatial, memory). Data are population mean normalized percentage (PM%) change from a 20-s baseline period before task initiation. Forty bilateral data sets were obtained (27 women, 37 right-hand dominant). All paradigms produced a sharp increase in CBFv in both dominant (PM% range: 3.29 to 9.70%) and nondominant (PM% range: 4.34 to 11.63%) hemispheres at task initiation, with associated increases in MAP (PM% range: 3.06 to 16.04%). ETCO2 did not differ significantly at task initiation (PM% range: -1.1 to 2.4%, P > 0.05). HR differed significantly across A and C tasks at initiation (PM% range: -1.1 to 2.4%, P < 0.05), but not B tasks. In conclusion, all tasks resulted in increases in CBFv, differing significantly between paradigms. These results require further investigation in a cognitively impaired population. NEW & NOTEWORTHY This study is the first to provide a normative data set of cerebral blood flow velocity (CBFv) responses to a complete cognitive assessment (Addenbrooke's Cognitive Examination, ACE-III) in a large sample ( n = 40) of healthy volunteers. All tasks produced peak and sustained increases in CBFv to different extents. The ACE-III is a feasible tool to assess neurovascular coupling with transcranial Doppler ultrasonography. These data can be used to inform the most appropriate cognitive task to elicit CBFv responses for future studies.

Assessment of the Brain's Macro- and Micro-Circulatory Blood Flow Responses to CO2 via Transfer Function Analysis.

Objectives: At present, there is no standard bedside method for assessing cerebral autoregulation (CA) with high temporal resolution. We combined the two methods most commonly used for this purpose, transcranial Doppler sonography (TCD, macro-circulation level), and near-infrared spectroscopy (NIRS, micro-circulation level), in an attempt to identify the most promising approach.Methods: In eight healthy subjects (5 women; mean age, 38 ± 10 years), CA disturbance was achieved by adding carbon dioxide (CO2) to the breathing air. We simultaneously recorded end-tidal CO2 (ETCO2), blood pressure (BP; non-invasively at the fingertip), and cerebral blood flow velocity (CBFV) in both middle cerebral arteries using TCD and determined oxygenated and deoxygenated hemoglobin levels using NIRS. For the analysis, we used transfer function calculations in the low-frequency band (0.07–0.15 Hz) to compare BP–CBFV, BP–oxygenated hemoglobin (OxHb), BP–tissue oxygenation index (TOI), CBFV–OxHb, and CBFV–TOI.Results: ETCO2 increased from 37 ± 2 to 44 ± 3 mmHg. The CO2-induced CBFV increase significantly correlated with the OxHb increase (R2 = 0.526, p < 0.001). Compared with baseline, the mean CO2 administration phase shift (in radians) significantly increased (p < 0.005) from –0.67 ± 0.20 to –0.51 ± 0.25 in the BP–CBFV system, and decreased from 1.21 ± 0.81 to −0.05 ± 0.91 in the CBFV–OxHb system, and from 0.94 ± 1.22 to −0.24 ± 1.0 in the CBFV–TOI system; no change was observed for BP–OxHb (0.38 ± 1.17 to 0.41 ± 1.42). Gain changed significantly only in the BP–CBFV system. The correlation between the ETCO2 change and phase change was higher in the CBFV–OxHb system [r = −0.60; 95% confidence interval (CI): −0.16, −0.84; p < 0.01] than in the BP–CBFV system (r = 0.52; 95% CI: 0.03, 0.08; p < 0.05).Conclusion: The transfer function characterizes the blood flow transition from macro- to micro-circulation by time delay only. The CBFV–OxHb system response with a broader phase shift distribution offers the prospect of a more detailed grading of CA responses. Whether this is of clinical relevance needs further studies in different patient populations.

Discordant results from global versus local cerebral blood flow measurements in response to rhythmic handgrip exercise

BackgroundThe cerebral blood flow (CBF) response to exercise can be measured in a larger vessel such as the middle cerebral artery (MCA; e.g. by transcranial Doppler; TCD) and at tissue level by e.g. arterial spin labeling MRI (ASL). The reported changes in total CBF between artery flow and tissue flow approaches are, however, inconsistent [1]. The aim of the current study was to evaluate TCD and ASL measurements in response to the same protocol of rhythmic handgrip exercise in the same subjects, to determine into what degree large vessel blood flow measurements conform to local perfusion measures. As a second aim, the assumption of constant vessel cross‐sectional area (CSA) during handgrip exercise was assessed by high resolution MRI.MethodsOn 2 different sessions separated by 1 week, heart rate (HR) and end‐tidal CO2 (PETCO2) were recorded in 11 subjects (5 female) during rhythmic handgrip. Three 5‐minutes runs of rhythmic handgripping at 60% of maximal voluntary contraction were alternated with 5 minutes of rest. During the first session regional CBF velocity (CBFv) was measured in the MCA by TCD and during the second session tissue perfusion (CBFt) was determined with ASL (3T Philips MRI, 17 slices). The CSA of the contralateral MCA was assessed with the same exercise protocol in a separate cohort of subjects (n=11, 5 female) using direct 7 Tesla MRI observations (following [2]).ResultsIn response to rhythmic handgrip exercise, an increase in regional CBFv (5±6%, p&lt;0.01) and motor area CBFt (10±6%, p&lt;0.01) was demonstrated, while whole brain gray matter CBFt did not change (1±8% p=0.75). During both sessions, the increase in HR was similar (11±6% vs. 15±8%, p=0.81) whereas PETCO2 did not change. No differences in absolute resting values for HR (p=0.09) and mean arterial pressure (p=0.27) were observed. Resting PetCO2 was slightly higher (2.3mmHg, p&lt;0.01) during the MRI session.High resolution MR imaging demonstrated a decrease in the MCA CSA (−4.0±0.6%; p&lt;0.001) in response to handgrip, together with an increase in HR (11±1%, p&lt;0.001) whereas PETCO2 remained constant (p=0.72).DiscussionThe 10% CBFt increase as detected with ASL was restricted to the motor cortex, which represents only 2% of the total MCA flow‐territorial volume. When extrapolated to the total flow‐change within the MCA flow territory, this would represent only a 0.2% increase, as also confirmed by the non‐significant change of whole brain gray matter flow (1±8%). However, our TCD measurements indicated a 5% CBFv increase of the entire flow territory. These measures of CBF were therefore inconsistent and differed by a factor 25. The present findings could be explained by the observed vasoconstriction of the MCA, but also other physiological phenomena, such as arteriovenous shunts, or a breakdown of other assumptions of the applied technologies, such as flow profile changes might be involved. A limitation is that the two sub‐studies were performed in different subjects.ConclusionThis study demonstrates discordant results from global (TCD) and local (ASL) cerebral blood flow measurements in response to rhythmic handgrip exercise. The observed reduction in MCA CSA implicates that the blood flow velocity changes measured by TCD overestimate the effects of mild exercise on CBF. Further pinpointing the nature of these discordant results will help interpretation of TCD and ASL studies concerning regulation of CBF.Support or Funding InformationThis study is supported by the Rembrandt Institute of Cardiovascular Science

Regional differences in the cerebral blood flow velocity response to hypobaric hypoxia at high altitudes.

Symptoms of acute mountain sickness (AMS) may appear above 2,500 m altitude, if the time allowed for acclimatization is insufficient. As the mechanisms underlying brain adaptation to the hypobaric hypoxic environment are not fully understood, a prospective study was performed investigating neurophysiological changes by means of near infrared spectroscopy, electroencephalograpy (EEG), and transcranial doppler sonography at 100, 3,440 and 5,050 m above sea level in the Khumbu Himal, Nepal. Fourteen of the 26 mountaineers reaching 5,050 m altitude developed symptoms of AMS between 3,440 and 5,050 m altitude (Lake-Louise Score ⩾3). Their EEG frontal beta activity and occipital alpha activity increased between 100 and 3,440 m altitude, i.e., before symptoms appeared. Cerebral blood flow velocity (CBFV) in the anterior and middle cerebral arteries (MCAs) increased in all mountaineers between 100 and 3,440 m altitude. During further ascent to 5,050 altitude, mountaineers with AMS developed a further increase in CBFV in the MCA, whereas in all mountaineers CBFV decreased continuously with increasing altitude in the posterior cerebral arteries. These results indicate that hypobaric hypoxia causes different regional changes in CBFV despite similar electrophysiological changes.

Measuring cerebral hemodynamic changes during action observation with functional transcranial doppler

[Purpose] The purpose of this study was to investigate the effects of action observation training (AOT) on cerebral hemodynamic changes including cerebral blood flow velocity (CBFV) and cerebral blood flow volume (CBFvol) in healthy subjects. [Subjects] Fifteen healthy subjects participated in this study. [Methods] All subjects were educated regarding AOT, and systolic peak velocity (Vs) as well as mean flow velocity (Vm) in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and posterior cerebral artery (PCA) were evaluated using functional transcranial doppler with a 2-MHz probe, before and after performing AOT. [Results] Healthy subjects showed significant differences in Vs and Vm in the MCA, ACA, and PCA after AOT compared with those before AOT. [Conclusion] Our findings indicate that AOT has a positive effect in terms of an increase in CBFV and CBFvol in healthy subjects, since the brain requires more blood to meet the metabolic demand during AOT.

Attenuated cerebral vasodilatory capacity in response to hypercapnia in college-aged African Americans.

African Americans (AAs) have increased risk for cardiovascular, cerebral vascular and metabolic disease, including hypertension, stroke, coronary artery disease, metabolic syndrome and type II diabetes, relative to Caucasian Americans (CAs). While it is accepted that endothelial function is impaired in AAs, less is known regarding their cerebral vasodilatory capacity in response to hypercapnia. We hypothesized that AAs have a reduction in the total range of change in cerebral blood flow velocity (CBFV) measured in the middle cerebral artery and an index of cerebral vascular conductance (CVCI) in response to changes in the partial pressure of end-tidal carbon dioxide () during rebreathing-induced hypercapnia when compared with CAs. Twenty-one healthy, college-aged AA (10 male) and 21 age- and sex-matched CA (10 male) subjects participated in this study. A four-parameter logistic regression was used for curve fitting the responses of CBFV and CVCI relative to changes in . The total ranges of change in CBFV (101 ± 18 versus 69 ± 23%; P < 0.001) and CVCI (83 ± 21 versus 58 ± 21%; P < 0.001) as well as the maximal increase in CBFV (205 ± 24 versus 169 ± 24%; P < 0.001) and CVCI (188 ± 30 versus 154 ± 19%; P < 0.001) were reduced during hypercapnia in AAs relative to CAs despite a similar increase in (change, 15 ± 3 versus 15 ± 3 mmHg; P = 0.65). In conclusion, these data indicate that AAs have attenuated cerebral vascular capacity to respond to hypercapnia when compared with CAs.

Cerebrovascular reactivity predicts stroke in high-grade carotid artery disease.

To assess the usefulness of transcranial Doppler CO2 reactivity (CO2R) for prediction of ipsilateral ischemic stroke in carotid artery stenosis and occlusion with a meta-analysis of prospective studies based on individual patient data. We searched Medline, Biosis Previews, Science Citation Index, The Cochrane Library, and EMBASE for studies in which patients with severe carotid artery stenosis or occlusion underwent Doppler CO2R testing (inhalation of CO2 or breath-holding) and were prospectively followed for ipsilateral ischemic stroke. Individual data from 754 patients from 9 studies were included. We used percentage cerebral blood flow velocity increase (pCi) during hypercapnia as the primary CO2R measure, and defined impaired reactivity as pCi <20% increase. In a multiple regression model, impaired CO2R was independently associated with an increased risk of ipsilateral ischemic stroke (hazard ratio [HR] 3.69; confidence interval [CI] 2.01, 6.77; p < 0.0001). Risk prediction was similar for recently symptomatic vs asymptomatic patients. Using continuous values of pCi, a significant association between decreasing pCi and increasing risk of ipsilateral stroke was found: HR of 1.64 (95% CI 1.33, 2.02; p < 0.0001) per 10% decrease in pCi. For patients with asymptomatic internal carotid artery stenosis only (n = 330), a comparable stroke risk prediction was found: increasing HR 1.95 (95% CI 1.26, 3.04; p = 0.003) per 10% decrease in pCi. This analysis supports the usefulness of CO2R in risk prediction for patients with severe carotid artery stenosis or occlusion, both in recently symptomatic and asymptomatic patients. Further studies should evaluate whether treatment strategies in asymptomatic patients based on CO2R could improve patient outcomes.

Improving the sensitivity of neurovascular coupling assessment using motor‐cognitive paradigms post‐stroke (1068.4)

Neurovascular coupling (NVC) has been used as an index of synaptic activity in health and disease. Cerebral blood flow velocity (CBFv) responses to neural stimulation can be misleading due to influences from peripheral co‐variates, leading to inaccurate NVC assessment. A dynamic multivariate autoregressive‐moving average (ARMA) model was used to calculate the contributions of blood pressure (BP), PaCO2 and the stimulus itself to changes in CBFv during active (AP), passive (PP) and motor imagery (MIP) paradigms of elbow flexion/ extension. Continuous recordings of CBFv, BP, heart rate and end‐tidal CO2 were performed in 20 stroke patients and 17 control subjects during the three paradigms. Though the paradigms led to a significant bilateral CBFv increase in both groups, differences between stroke and controls were found only during the PP (p=0.02). ARMA analysis revealed a marked BP contribution to the initial peaked CBFv response in both groups during all paradigms, as well as a decrease in the amplitude of the stimulation component after stroke (p&lt;0.001). PaCO2 did not interfere with the CBFv responses during either the MIP in controls or any of the paradigms in the stroke group. However, the responses to AP and MIP in controls were influenced by a significant reduction in PaCO2 (AP reduction of 2%; MIP reduction of 2.5%). By removing the influences of BP and PaCO2, it was possible to detect differences in the effects of stimulation between controls and strokes. We concluded that, independent of the paradigm adopted for NVC assessment, factoring out the influences of BP and PaCO2 can lead to improvements in sensitivity.Grant Funding Source: CAPES ‐ Ministry of Education of Brazil

Effect of oxygen inhalation on cerebral blood flow velocity in premature neonates

The study tested the hypothesis that hyperoxemia and hypoxemia differentially alter cerebral blood flow velocity (CBFV) in a gestational age-dependent manner. Cases comprised 98 neonates with mild respiratory distress, receiving oxygen for >24 h in first 48 h of life. Ninety-eight age- and-weight-matched healthy neonates served as controls. Infants with perinatal asphyxia, shock, sepsis, malformations, acidosis/alkalosis, and hypo/hypercarbia were excluded. Resistance index (RI), pulsatility index (PI), peak systolic flow velocity (PSV), and vascular diameter were measured in internal carotid, vertebral, and middle cerebral arteries by transcranial doppler ultrasonography between 24 and 48 h of life with immediate postdoppler arterial blood gas analysis. For subgroup analysis, neonates were divided by gestational age and PaO2. An overall decrease in RI/PI and increase in PSV and vasodilation was observed in cases. Hyperoxemia (PaO2 >90 mm Hg) was more common in premature neonates. Neonates <32 wk showed an increase in CBFV (decreased RI/PI and increased PSV/diameter) in association with hyperoxemia. An opposite response was observed in neonates ≥ 32 wk, where CBFV increased in response to hypoxemia (PaO2 <50 mm Hg) and decreased in hyperoxemia. Increased CBFV showed high predictive accuracy for immediate mortality and intracranial hemorrhage. Depending on gestational maturity, hyperoxemia or hypoxemia produce differential effects in CBFV.

Difference in cerebral blood flow velocity in neonates with and without hyperbilirubinemia

PurposeTo evaluate the difference in cerebral blood flow velocity (CBFV) in neonates with and without hyperbilirubinemia. MethodsCBFV of 70 healthy late-preterm and term newborns with unconjugated hyperbilirubinemia (UCH) reaching the threshold of phototherapy requirement was compared with 70 gestational- and postnatal age-matched controls without hyperbilirubinemia. Resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV) and vascular diameter were measured in internal carotid, vertebral and middle cerebral arteries by transcranial color Doppler ultrasound at the beginning of phototherapy, after 48–72h of starting phototherapy and at 5–7days after its stoppage. In controls CBFV was assessed once at inclusion. ResultsBoth the groups were comparable. An increase in CBFV (decreased RI and PI, increased PSV and vasodilation) was observed in the UCH group. A further increase in CBFV was noticed after 48h of phototherapy. After 5–7days of stoppage of phototherapy, though there was a significant reduction in CBFV in mild-to-moderate UCH (serum bilirubin ⩽25mg/dL), in severe UCH (serum bilirubin >25mg/dL), CBFV remained increased. Four neonates developed features of acute bilirubin encephalopathy and had significantly higher CBFV compared to those with normal outcome. ConclusionsAn increase in CBFV was observed in neonates with UCH compared to those without hyperbilirubinemia.

Cerebral blood flow velocity in asymptomatic premature neonates exposed to clinical chorioamnionitis

AimsTo test the hypothesis that cerebral blood flow velocity (CBFV) is altered in asymptomatic premature neonates exposed to clinical chorioamnionitis. MethodsThis prospective observational study included 30 premature (<34 weeks) neonates who were exposed to clinical chorioamnionitis but did not develop any feature of early-onset neonatal sepsis. Thirty gestational-age matched healthy neonates served as controls. Cord blood interleukin (IL)-6 concentrations were measured at birth. Resistance index (RI), pulsatility index (PI), peak systolic flow velocity and vascular diameter of internal carotid, vertebral and middle cerebral arteries were measured by transcranial color doppler ultrasonography within 48 h of delivery. The infants were followed up clinically after discharge and magnetic resonance imaging (MRI) was done at the corrected age of 6 months. ResultsConventional sepsis screen and blood culture was negative in all. Significantly higher cord blood IL-6 concentrations, lower resistance (RI and PI) and higher blood flow with vasodilation were recorded in all cerebral arteries of the chorioamnionitis group. Significant correlation was observed between the increase in CBFV and the increase of IL-6 concentrations. At the age of 6 months, two cases showed features of delayed developmental milestone and periventricular leucomalacia in MRI. ConclusionsAsymptomatic premature neonates exposed to clinical chorioamnionitis had significantly increased cord blood IL-6 concentrations and CBFV. The utility of increased CBFV as a predictor of adverse neurodevelopmental outcome may be tested in a well designed longitudinal study with larger sample size.

Cerebral blood flow response to neural activation after acute ischemic stroke: a failure of myogenic regulation?

We tested two hypotheses: (1) neurovascular coupling is impaired after acute ischemic stroke, (2) subcomponent analysis of cerebral blood flow velocity can reveal significant differences between acute ischemic stroke and healthy controls. This was explored through the comparison of nineteen acute ischemic stroke patients with healthy controls. Recordings of cerebral blood flow velocity, blood pressure and end-tidal CO2 were obtained during 60s of passive elbow flexion. Cerebral blood flow velocity changes were decomposed into standardized subcomponents describing the contributions of blood pressure (V BP), resistance area product (V RAP) and critical closing pressure (V CrCP). The passive paradigm led to a bilateral cerebral blood flow velocity increase in both groups, but in acute ischemic stroke the magnitude of change was significantly lower. Blood pressure increases were shown to be an important contributor to cerebral blood flow velocity response throughout the paradigm in both groups, with no significant difference between groups. The V CrCP contribution was not different between groups or hemispheres; its continuous rise during activation indicating a vasodilatory effect. On the other hand, the V RAP contribution showed significant differences (p = 0.03), thus suggesting myogenic impairment in acute ischemic stroke. Cerebral blood flow velocity responses to passive elbow flexion suggest an impairment of neurovascular coupling in acute ischemic stroke. Subcomponent analysis suggests an impairment of the myogenic pathways, giving a greater insight into the different mechanisms contributing to neurovascular coupling. Further research is needed to assess the clinical value of subcomponent analysis of neurovascular coupling and the natural history of such changes following acute ischemic stroke.

Does hypercapnia-induced impairment of cerebral autoregulation affect neurovascular coupling? A functional TCD study

Neurovascular coupling (NVC) and dynamic cerebral autoregulation (dCA) are both impaired in the acute phase of ischemic stroke, but their reciprocal interactions are difficult to predict. To clarify these aspects, the present study explored NVC in a healthy volunteer population during a surrogate state of impaired dCA induced by hypercapnia. This study aimed to test whether hypercapnia leads to a depression of NVC through an impairment of dCA. Continuous recordings of middle cerebral arteries cerebral blood flow velocity (CBFv), blood pressure (BP), heart rate, and end-tidal CO2 were performed in 19 right-handed subjects (aged >45 yr) before, during, and after 60 s of a passive paradigm during normocapnia and hypercapnia. The CBFv response was broken down into subcomponents describing the relative contributions of BP (VBP), critical closing pressure (VCrCP), and resistance area product (VRAP). VRAP reflects myogenic activity in response to BP changes, whereas VCrCP is more indicative of metabolic control. The results revealed that hypercapnia significantly affected NVC, with significant reductions in the relative contribution of VCrCP to the paradigm-induced increase in CBFv. The present study suggests that hypercapnia impairs both dCA and NVC, probably acting through an impairment of the metabolic component of CBF control.

Middle cerebral O2 delivery during the modified Oxford maneuver increases with sodium nitroprusside and decreases during phenylephrine

The modified Oxford maneuver is the reference standard for assessing arterial baroreflex function. The maneuver comprises a systemic bolus injection of 100 μg sodium nitroprusside (SNP) followed by 150 μg phenylephrine (PE). On the one hand, this results in an increase in oxyhemoglobin and total hemoglobin followed by a decrease within the cerebral sample volume illuminated by near-infrared spectroscopy (NIRS). On the other hand, it produces a decrease in cerebral blood flow velocity (CBFv) within the middle cerebral artery (MCA) during SNP and an increase in CBFv during PE as measured by transcranial Doppler ultrasound. To resolve this apparent discrepancy, we hypothesized that SNP dilates, whereas PE constricts, the MCA. We combined transcranial Doppler ultrasound of the right MCA with NIRS illuminating the right frontal cortex in 12 supine healthy subjects 18-24 yr old. Assuming constant O₂ consumption and venous saturation, as estimated by partial venous occlusion plethysmography, we used conservation of mass (continuity) equations to estimate the changes in arterial inflow (ΔQa) and venous outflow (ΔQv) of the NIRS-illuminated area. Oxyhemoglobin and total hemoglobin, respectively, increased by 13.6 ± 1.6 and 15.2 ± 1.4 μmol/kg brain tissue with SNP despite hypotension and decreased by 6 ± 1 and 7 ± 1 μmol/kg with PE despite hypertension. SNP increased ΔQa by 0.36 ± .03 μmol·kg(-1)·s(-1) (21.6 μmol·kg(-1)·min(-1)), whereas CBFv decreased from 71 ± 2 to 62 ± 2 cm/s. PE decreased ΔQa by 0.27 ± .2 μmol·kg(-1)·s(-1) (16.2 μmol·kg(-1)·min(-1)), whereas CBFv increased to 75 ± 3 cm/s. These results are consistent with dilation of the MCA by SNP and constriction by PE.