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Biomedical subjects

R Aaslid

Publications and source records attributed to R Aaslid.

At least 19 recordsLinked to original sources

Dynamic cerebral autoregulation in healthy adolescents.

BACKGROUND: : There is little information on the limits of cerebral autoregulation and the autoregulatory capacity in children. The aim of this study was to compare dynamic cerebral autoregulation between healthy adolescents and adults. METHODS: : Seventeen healthy volunteers 12-17 years (n = 8) and 25-45 years (n = 9) were enrolled in this study. Bilateral mean middle cerebral artery flow velocities (Vmca; (cm/s)) were measured using transcranial Doppler ultrasonography (TCD). Mean arterial blood pressure (MAP) and end-tidal carbon dioxide were measured continuously during dynamic cerebral autoregulation studies. Blood pressure cuffs were placed around both thighs and inflated to 30 mmHg above the systolic blood pressure for 3 min and then rapidly deflated, resulting in transient systemic hypotension. The change of Vmca to change in MAP constitutes the autoregulatory response, and the speed of this response was quantified using computer model parameter estimation. The dynamic autoregulatory index (ARI) was averaged between the two sides. RESULTS: : Adolescents had significantly lower ARI (3.9 +/- 2.1 vs. 5.3 +/- 0.8; P=0.05), and higher Vmca (75.2 +/- 15.2 vs. 57.6 +/- 15.0; P<0.001) than adults. CONCLUSION: : The autoregulatory index is physiologically lower in normal adolescents 12-17 years of age than in adults.

Adolescent↗

Hemodynamics of cerebrovascular spasm.

An understanding of the hemodynamics of cerebrovascular spasm following subarachnoid hemorrhage is important for the diagnosis and treatment of this potentially dangerous condition. An overview model is presented which includes the main elements determining the overall effect of vasospasm. The model included realistic pressure-flow-velocity-diameter relationship encountered in a geometry resembling that of vasospasm of the middle cerebral artery. Viscosity was adjusted to that expected of human blood. Furthermore, a realistic model the cerebral autoregulation was included. The effects of induced hypertension as well as hypotension were studied. It was found that the friction pressure loss in the spastic segment was 3.5 times as high as that predicted by using the Hagen-Poiseuille formula. The reason for this discrepancy was probably the 'inlet length effect' considerably increasing the friction. Furthermore, including the Bernoulli kinetic pressure energy, a formula was proposed that accurately described the experimental data. From this hemodynamic perspective, strong support was found for the present trend to use aggressive hypertensive therapy in patients with vasospasm. The results also confirmed that TCD velocity measurements in the spastic segment when taken alone may not be a good index of the degree and effect of the spasm. These measurements must be combined with other techniques such as extracranial Doppler or CBF to assess the degree of spasm.

Brain↗

The influence of different gases on acoustic properties of a spherosome-based ultrasound contrast agent (BY963). A transcranial Dopplersonography study.

Ultrasound contrast agents improve the signal-to-noise ratio of reflected ultrasound, enhancing the diagnostic value of transcranial Doppler (TCD). In dog studies, we investigated the time course of TCD signal amplitude after application of a phospholipid-containing ultrasound contrast agent (BY963) filled with different gases. The median time of Doppler amplitude enhancement exceeding 5 dB was determined using isoflurane-, isopentane-, trichlortrifluoroethane-, air-, argon-, and perfluoropentane-filled BY963 (69, 72, 75, 78, 88, and 245 seconds respectively). The decrease of time-intensity curve and the duration of signal enhancement showed significant differences comparing the different gases (p = 0.04 and 0.03, respectively). The time course of in vitro stability of BY963 agitated with the different gases measured by absorbance of light (500 nm) showed a retarded decay for perfluoropentane, a rapid decrease for air, isopentane, trichlortrifluoroethane, and argon, and a very rapid decrease using isoflurane. The time course of the different gases depended on the physiochemical properties (lipophilicity and the solubility in water) of the gas encoated in the phospholipid shell. Perfluoropentane-filled BY963 showed the highest in vitro stability and the longest duration of TCD enhancement compared with the other gases used.

Acoustics↗

Evaluation of hemodynamic responses in head injury patients with transcranial Doppler monitoring.

Transcranial Doppler (TCD) can monitor middle cerebral artery (MCA) velocity which can be recorded simultaneously with other physiologic parameters such as end tidal (Et) CO2, arterial blood pressure and intracranial pressure (ICP), in head injured patients. Relative changes in MCA velocity can be used to reflect relative MCA blood flow changes during ICP waves, and also to evaluate cerebral autoregulation, CO2 reactivity and hemodynamic responses to mannitol and barbiturates. The utility and practicality of short intervals of TCD monitoring to evaluate hemodynamic responses, was evaluated in a group of 22 head injured patients (average Glasgow coma score 6). During ICP A waves, MCA velocity always decreased during the peak of the wave, and during ICP B waves, fluctuated synchronously with the ICP. Dynamic cerebral autoregulation, and reactivity to CO2, were reduced within 48 hours of admission. Impaired cerebral autoregulation within 48 hours of admission did not correlate with outcome at 1 month. Mannitol infusion caused an increase in MCA velocity (15.4 +/- 7.9%) which was significantly correlated to the impairment of dynamic autoregulation (r = 0.54, p < 0.0001). The MCA velocity response to a test dose of barbiturates was significantly correlated to the ICP (r = 0.61, p < 0.01) response as well as to the CO2 reactivity (r = 0.37, p < 0.05). Continuous MCA velocity monitoring using TCD may be useful in evaluating a variety of hemodynamic responses in head injury patients and may replace more cumbersome cerebral blood flow techniques which have been used in the past for these purposes.

Adolescent↗

Cerebral autoregulation following minor head injury.

The purpose of this study was to determine whether patients with minor head injury experience impairments in cerebral autoregulation. Twenty-nine patients with minor head injuries defined by Glasgow Coma Scale (GCS) scores of 13 to 15 underwent testing of dynamic cerebral autoregulation within 48 hours of their injury using continuous transcranial Doppler velocity recordings and blood pressure recordings. Twenty-nine age-matched normal volunteers underwent autoregulation testing in the same manner to establish comparison values. The function of the autoregulatory response was assessed by the cerebral blood flow velocity response to induced rapid brief changes in arterial blood pressure and measured as the autoregulation index (ARI). Eight (28%) of the 29 patients with minor head injury demonstrated poorly functioning or absent cerebral autoregulation versus none of the controls, and this difference was highly significant (p = 0.008). A significant correlation between lower blood pressure and worse autoregulation was found by regression analysis in head-injured patients (r = 0.6, p < 0.001); however, lower blood pressure did not account for the autoregulatory impairment in all patients. Within this group of head-injured patients there was no correlation between ARI and initial GCS or 1-month Glasgow Outcome Scale scores. This study indicates that a significant number of patients with minor head injury may have impaired cerebral autoregulation and may be at increased risk for secondary ischemic neuronal damage.

Adolescent↗

Effect of transient moderate hyperventilation on dynamic cerebral autoregulation after severe head injury.

OBJECTIVE: This study was undertaken to evaluate the effect of acute moderate hyperventilation on cerebral autoregulation in head-injured patients. METHODS: Dynamic cerebral autoregulation was analyzed by use of transcranial doppler ultrasonography before and after hyperventilation in 10 patients with severe head injury. All of the patients were artificially ventilated and underwent continuous monitoring of arterial blood pressure, intracranial pressure, and end-tidal carbon dioxide. To test autoregulation, rapid transient decreases in systemic blood pressure were achieved by quickly releasing large blood pressure cuffs that were inflated around both thighs. This resulted in a drop of 24 +/- 6 mm Hg in mean systemic blood pressure, which lasted an average of 49 +/- 24 seconds. Cerebral blood flow velocity was monitored continuously in both middle cerebral arteries by use of transcranial doppler ultrasonography. The percentage change in middle cerebral artery velocity was used as an index of the change in cerebral blood flow during the autoregulatory response. The change in estimated cerebrovascular resistance, immediately after the blood pressure drop, or the rate of regulation was used to analyze the effectiveness of the cerebral autoregulation. This value was calculated by determining the rate of increase in middle cerebral artery velocity during the 1st 5 seconds after a blood pressure drop, relative to the rate of increase of the cerebral perfusion pressure. RESULTS: The average rate of regulation during normocapnia at pCO2 of 37 mm Hg was 11.4 +/- 5% per second. After reduction of the pCO2 to 28 mm Hg, the average rate of regulation improved significantly (P < 0.001) to 17.7 +/- 6% per second. Autoregulation improved, despite no significant change in the cerebral perfusion pressure during hyperventilation. The degree of improvement in autoregulation was significantly correlated with the CO2 reactivity (r = 0.45, P < 0.05) but did not correlate (r = -0.23, P = 0.33) with the change in arterial pH value after hyperventilation. CONCLUSION: These results confirm the finding that dynamic autoregulation is disturbed in severe head injury and that moderate transient hyperventilation can temporarily improve the efficiency of the autoregulatory response, probably as a result of a transient increase in vascular tone.

Acid-Base Equilibrium↗

Visually evoked blood flow response assessed by simultaneous two-channel transcranial Doppler using flow velocity averaging.

BACKGROUND AND PURPOSE: We assessed the influence of different visual stimuli and the reproducibility and habituation of evoked flow responses using simultaneous two-channel transcranial Doppler monitoring and flow velocity averaging. METHODS: We measured stimulus-related percentage changes in posterior cerebral, basilar, and middle cerebral artery blood flow velocities in 14 normal volunteers using stimulus-triggered velocity averaging. With a two-channel transcranial Doppler system, simultaneous measurements in two arteries (both posterior cerebral arteries and the basilar and middle cerebral artery) were taken using multiple-array light-emitting diodes applying flash stimuli. Both posterior cerebral arteries were monitored to assess reproducibility and habituation of the evoked response with repetitive measurements under unchanged conditions and to analyze the influence of different features of the visual stimulus. RESULTS: There was a distinctive increase in velocities resulting from visual stimuli in both posterior cerebral and the basilar arteries but not in the middle cerebral artery. The responses in both posterior cerebral arteries were larger than in the basilar artery (P = .0001). Brightness (P < .0001), as well as complexity (P < .0001), of the visual stimulus had a significant influence on the response amplitude. There was a trend toward a greater right-sided activation. Amplitudes of the evoked response were very stable during repetitive testing (coefficient of variation of the difference was 0.6). There was a trend toward habituation with monotonous (flash) but not with complex visual stimuli. A "zero" stimulus produced no responses. CONCLUSIONS: The use of flow velocity averaging and two-channel simultaneous recording increases the sensitivity of transcranial Doppler monitoring to detect and correlate selective flow changes in the posterior cerebral arteries resulting from cerebral activation produced by visual stimulation.

Adult↗

Transcranial color-coded duplex sonography, magnetic resonance angiography, and computed tomography angiography: methods, applications, advantages, and limitations.

Transcranial color-coded duplex sonography (TCCD), magnetic resonance angiography (MRA), and computed tomography angiography (CTA) are novel noninvasive or minimally invasive techniques for the study of the intracranial circulation. TCCD is relatively inexpensive and permits bedside examination. It improves the accuracy and reliability of conventional transcranial Doppler studies. The main limitation of TCCD are the ultrasonic windows. They restrict the area of insonation to the major cerebral arteries and the proximal part of its branches, lower the spatial resolution, and may prevent transtemporal insonation. Using MRA, both large and small intracranial arteries and veins can be imaged by selecting the appropriate imaging parameters. MRA provides morphologic information about the cerebral vessels, relying on blood flow as the physical basis for generating contrast between stationary tissues and moving spins. MRA is highly sensitive for the detection of occlusive disease in large intracranial arteries. However, with bright blood techniques the degree of stenosis tends to be exaggerated. Flow direction, eg, in collaterals, can be determined by selective or phase-contrast MRA. Perfusion imaging techniques provide information about blood flow at the capillary level. Diffusion imaging depicts molecular motion. TCCD and MRA used in combination or alone may eliminate the need for intra-arterial digital subtraction angiography (DSA) in most patients studied for occlusive cerebrovascular disease. DSA may be reserved for those patients where there is disagreement among the noninvasive techniques, and for the diagnosis of cerebral aneurysms and arteriovenous malformations. CTA relies on spiral CT technology and intravenous contrast injection. To date, intracranial use has been predominantly for the diagnosis of aneurysms. The role of CTA for the detection of nonaneurysmal intracranial vascular disease has yet to be established.

Adult↗

Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia.

BACKGROUND: Although inhalation anesthetic agents are thought to impair cerebral autoregulation more than intravenous agents, there are few controlled studies in humans. METHODS: In the first group (n = 24), dynamic autoregulation was assessed from the response of middle cerebral artery blood flow velocity (Vmca) to a transient step decrease in mean arterial blood pressure (MABP). The transient hypotension was induced by rapid deflation of thigh cuffs after inflation for 3 min. In the second group (n = 18), static autoregulation was studied by observing Vmca in response to a phenylephrine-induced increase in MABP. All patients were studied during fentanyl (3 micrograms.kg-1.h-1)/nitrous oxide (70%) anesthesia, followed by, in a randomized manner, isoflurane, desflurane, or propofol in a low dose (0.5 MAC or 100 micrograms.kg-1.min-1) and a high dose (1.5 MAC or 200 micrograms.kg-1.min-1). The dynamic rate of regulation (dROR) was assessed from the rate of change in cerebrovascular resistance (MABP/Vmca) with the blood pressure decreases using computer modeling, whereas the static rate of regulation (sROR) was assessed from the change in Vmca with the change in MABP. RESULTS: Low-dose isoflurane delayed (dROR decreased) but did not reduce the autoregulatory response (sROR intact). Low-dose desflurane decreased both dROR and sROR. During 1.5 MAC isoflurane or desflurane, autoregulation was ablated (both dROR and sROR impaired). Neither dROR nor sROR changed with low- or high-dose propofol. CONCLUSIONS: At 1.5 MAC, isoflurane and desflurane impaired autoregulation whereas propofol (200 micrograms.kg-1.min-1) preserved it.

Adult↗

Comparison of static and dynamic cerebral autoregulation measurements.

BACKGROUND AND PURPOSE: Cerebral autoregulation can be evaluated by measuring relative blood flow changes in response to a steady-state change in the blood pressure (static method) or during the response to a rapid change in blood pressure (dynamic method). The purpose of this study was to compare the results of the two methods in humans with both intact and impaired autoregulatory capacity. METHODS: Using intraoperative transcranial Doppler sonography recordings from both middle cerebral arteries, we determined static and dynamic autoregulatory responses in 10 normal subjects undergoing elective surgical procedures. The changes in cerebrovascular resistance were estimated from the changes in cerebral blood flow velocity and arterial blood pressure in response to manipulations of blood pressure. Static autoregulation was determined by analyzing the response to a phenylephrine-induced rise in blood pressure, whereas rapid deflation of a blood pressure cuff around one thigh served as a stimulus for testing dynamic autoregulation. Both measurements were performed in patients with intact autoregulation during propofol anesthesia and again in the same patients after autoregulation had been impaired by administration of high-dose isoflurane. RESULTS: There was a significant reduction in autoregulatory capacity after the administration of high-dose isoflurane, which could be demonstrated using static (P < .0001) and dynamic (P < .0001) methods. The correlation between static or steady-state and dynamic autoregulation measurements was highly significant (r = .93, P < .0001). CONCLUSIONS: These data show that in normal human subjects measurement of dynamic autoregulation yields similar results as static testing of intact and pharmacologically impaired autoregulation.

Adult↗

Estimates of pulse wave velocity and measurement of pulse transit time in the human cerebral circulation.

Knowledge of the velocity with which pressure and flow waves travel within the arterial tree has been fundamental to the understanding of important hemodynamic parameters, such as vessel wall elastance, impedance and reflection coefficients for the systemic circulation. To our knowledge, however, this pulse wave velocity (PWV) has not been previously measured for the human cerebral circulation. In this study, we estimate the PWV from 88 measurements during normocarbia and 95 measurements during hypocarbia in six healthy human volunteers. The measurements consisted of time delays between velocity waveforms obtained simultaneously from the cervical carotid artery and the ipsilateral middle cerebral artery. An estimation of the distance between these sites as 10 centimeters yielded a PWV of 12.8 m/s for both levels of pCO2. Vessel elasticity could then be estimated between 17 and 34 dyne/cm2.10(6). These values of PWV are among the highest of those found in the peripheral circulation, and may have implications for the interpretation of the shape of the cerebral pressure and flow waveforms.

Adult↗

Comparison of flow and velocity during dynamic autoregulation testing in humans.

BACKGROUND AND PURPOSE: We compared relative changes in middle cerebral artery velocity and internal carotid artery flow during autoregulation testing to test the validity of using transcranial Doppler recordings of middle cerebral artery velocity to evaluate cerebral autoregulation in humans. METHODS: Seven human volunteers had dynamic autoregulation tested during surgical procedures that included exposure of the internal carotid artery. The mean arterial blood pressure and middle cerebral artery velocity spectral outline (Vmax), using transcranial Doppler, and ipsilateral internal carotid artery flow, using an electromagnetic flowmeter, were continuously and simultaneously recorded during transient sharp decreases in blood pressure that were induced by rapid deflation of thigh blood pressure cuffs. The resulting responses of velocity in the middle cerebral artery and flow in the internal carotid artery were compared. RESULTS: Moderate decreases in blood pressure evoked responses in cerebral autoregulation. There were no significant (P = .97) differences between the responses in middle cerebral artery velocity and internal carotid artery flow to the blood pressure decreases. CONCLUSIONS: Relative changes in Vmax accurately reflect relative changes in internal carotid artery flow during dynamic autoregulation testing in humans. Therefore, alterations in middle cerebral artery diameter do not occur to the extent that they introduce a significant error in making these comparisons.

Aged↗

Transcranial Doppler monitoring in head injury: relations between type of injury, flow velocities, vasoreactivity, and outcome.

Eighty-six patients with head injuries with an admission Glasgow Coma Scale score between 3 and 12 were studied sequentially by transcranial and cervical Doppler sonography. On a subset of 26 patients, sequential autoregulation and CO2 reactivity testing was also performed. Patient characteristics and hemodynamic data were correlated and analyzed with respect to the final outcome. The internal carotid artery (ICA) and middle cerebral artery flow velocities followed a typical pattern. Both were depressed during the first 3 days after the trauma and then increased to a maximum between Days 5 and 7. The increase of the middle cerebral artery flow velocities was more pronounced than the increase of the ICA flow velocities, thus indicating some degree of vasospasm. The amount of subarachnoid hemorrhage on the initial computed tomography correlated with the average middle cerebral artery/ICA flow velocity ratio (r = 0.5). Subarachnoid hemorrhages on computed tomography and, to a lesser degree, subdural and intracerebral hematomas were correlated with an unfavorable outcome. Vasospasm remained subcritical, and no negative relationship to outcome could be identified. Hyperperfusion, as based on ICA flow velocities, and vasospasm were correlated with diminished vasoreactivity. However, disturbed vasoreactivities, particularly during the first days, were common and did not necessarily predict an unfavorable outcome.

Adolescent↗

Dynamic computed tomographic imaging of regional cerebral blood flow and blood volume. A clinical pilot study.

BACKGROUND AND PURPOSE: The advent of faster computed tomography scanners has evoked considerable interest in using this technology as a more practical method of regional cerebral hemodynamic evaluation than the currently available positron emission and single-photon emission computed tomography. The theoretical concepts have been worked out and validated in the laboratory by several groups. The aim of the present study was the development of a clinically useful system. METHODS: Software was developed for dynamic computed tomography-based calculation and color-coded representation of regional cerebral blood flow and blood volume. Normal values, reproducibility, and sensitivity to acetazolamide challenge were established in 13 volunteers. The method was applied to an additional three patients with internal carotid artery occlusion and known decreased vascular reserve capacity as diagnosed by transcranial Doppler ultrasonography. RESULTS: Normal regional cerebral blood flow was determined as 50 +/- 13 ml/100 ml per minute and normal fractional cerebral blood volume as 58 +/- 12 ml/1,000 ml (mean +/- SD). In five volunteers, two examinations were performed within 15 minutes for determination of reproducibility. Intermeasurement variability of hemispheric blood flow and blood volume was determined as +/- 23% and +/- 16%, respectively. Intravenous administration of 1 g acetazolamide resulted on the average in a 75% increase of blood flow and a 65% increase of fractional blood volume. In the patients with decreased cerebrovascular reserve capacity, baseline fractional blood volume in the ischemic hemispheres was significantly increased. Baseline regional cerebral blood flow in the ischemic territories was overestimated. Reactivity to acetazolamide of both regional blood flow and fractional blood volume was clearly reduced in the ischemic hemispheres. CONCLUSIONS: The present results demonstrate that the method is a simple and effective means of determining regional cerebral blood volume. Spatial resolution is superior to that of the radioactive tracer methods. Hemodynamic evaluation of ischemic conditions can be performed on the basis of increased resting cerebral blood volume and a diminished increase after acetazolamide. Accuracy of cerebral blood flow measurements, on the other hand, is affected by abnormal cerebral blood volume, and corresponding adjustments need to be made in pathological conditions.

Acetazolamide↗

The relationship of blood flow velocity fluctuations to intracranial pressure B waves.

Intracranial pressure (ICP) and continuous transcranial Doppler ultrasound signals were monitored in 20 head-injured patients and simultaneous synchronous fluctuations of middle cerebral artery (MCA) velocity and B waves of the ICP were observed. Continuous simultaneous monitoring of MCA velocity, ICP, arterial blood pressure, and expired CO2 revealed that both velocity waves and B waves occurred despite a constant CO2 concentration in ventilated patients and were usually not accompanied by fluctuations in the arterial blood pressure. Additional recordings from the extracranial carotid artery during the ICP B waves revealed similar synchronous fluctuations in the velocity of this artery, strongly supporting the hypothesis that blood flow fluctuations produce the velocity waves. The ratio between ICP wave amplitude and velocity wave amplitude was highly correlated to the ICP (r = 0.81, p less than 0.001). Velocity waves of similar characteristics and frequency, but usually of shorter duration, were observed in seven of 10 normal subjects in whom MCA velocity was recorded for 1 hour. The findings in this report strongly suggest that B waves in the ICP are a secondary effect of vasomotor waves, producing cerebral blood flow fluctuations that become amplified in the ICP tracing, in states of reduced intracranial compliance.

Adolescent↗

Transcranial Doppler: clinical and experimental uses.

Blood flow velocity in the basal intracranial arteries can be reliably recorded using transcranial Doppler (TCD) ultrasonography. The utility of Doppler ultrasound in detecting stenosis of arteries has therefore been extended to include the intracranial basal arteries. This has been useful in detecting intracranial stenosis from a variety of causes including atherosclerosis and vasospasm induced by subarachnoid hemorrhage. Changes in cerebral hemodynamics during significantly increased intracranial pressure have also been detected, and have been useful in warning of compromise of the cerebral circulation in head injury. The assessment of the final hemodynamic effects of occlusive disease on the middle cerebral artery can be studied using the CO2 reactivity test. This offers additional diagnostic information in these patients. The direct detection of intracranial microemboli using TCD is also now possible and this has implications in the management of patients with stroke and transient ischemic attacks. Continuous monitoring of the middle cerebral artery velocity has been useful in indicating relative blood flow changes through this artery under certain specific circumstances. By providing continuous information on relative blood flow changes, the dynamics of the cerebral circulation can be studied in more detail. This has allowed the assessment of cerebral autoregulation, as well as blood flow changes, due to changes in cortical activity induced by visual stimulation. Further research on the dynamics of the human cerebral circulation will be possible using this technology.

Animals↗

Assessment of cerebral autoregulation dynamics from simultaneous arterial and venous transcranial Doppler recordings in humans.

We investigated the validity of transcranial Doppler recordings for the analysis of dynamic responses of cerebral autoregulation. We found no significant differences in percentage changes among maximal (centerline) blood flow velocity, cross-sectional mean blood flow velocity, and signal power-estimated blood flow during 24-mm Hg stepwise changes in arterial blood pressure. We investigated blood flow propagation delays in the cerebral circulation with simultaneous Doppler recordings from the middle cerebral artery and the straight sinus. The time for a stepwise decrease in blood flow to propagate through the cerebral circulation was only 200 msec. Brief (1.37-second) carotid artery compression tests also demonstrated that the volume compliance effects of the cerebral vascular bed were small, only about 2.2% of normal blood flow in 1 second. Furthermore, transients associated with inertial and volume compliance died out after 108 msec. We also investigated the hypothesis that autoregulatory responses are influenced by hyperventilation using the same brief carotid artery compressions. One second after release, the flow index increased by 17% during normocapnia and 36% during hypocapnia. After 5 seconds, the flow index demonstrated a clear oscillatory response during hypocapnia that was not seen during normocapnia. These results suggest that the intact human cerebral circulation in the absence of pharmacological influences does not function as predicted from pial vessel observations in animals.

Adult↗