Cerebral Blood Flow Velocity Oscillations Research Articles

A simple deep breathing test reveals altered cerebral autoregulation in type 2 diabetic patients

Patients with diabetes mellitus have an increased risk of stroke and other cerebrovascular complications. The purpose of this study was to evaluate the autoregulation of cerebral blood flow in diabetic patients using a simple method that could easily be applied to the clinical routine screening of diabetic patients. We studied ten patients with type 2 diabetes mellitus and 11 healthy volunteer control participants. Continuous and non-invasive measurements of blood pressure and cerebral blood flow velocity were performed during deep breathing at 0.1 Hz (six breaths per minute). Cerebral autoregulation was assessed from the phase shift angle between breathing-induced 0.1 Hz oscillations in mean blood pressure and cerebral blood flow velocity. The controls and patients all showed positive phase shift angles between breathing-induced 0.1 Hz blood pressure and cerebral blood flow velocity oscillations. However, the phase shift angle was significantly reduced (p < 0.05) in the patients (48 +/- 9 degrees ) compared with the controls (80 +/- 12 degrees ). The gain between 0.1 Hz oscillations in blood pressure and cerebral blood flow velocity did not differ significantly between the patients and controls. The reduced phase shift angle between oscillations in mean blood pressure and cerebral blood flow velocity during deep breathing suggests altered cerebral autoregulation in patients with diabetes and might contribute to an increased risk of cerebrovascular disorders.

Inspiratory resistance delays the reporting of symptoms with central hypovolemia: association with cerebral blood flow

We tested the hypothesis that breathing through an inspiratory threshold device (ITD) during progressive central hypovolemia would protect cerebral perfusion and attenuate the reporting of presyncopal symptoms. Eight human subjects were exposed to lower-body negative pressure (LBNP) until the presence of symptoms while breathing through either an active ITD (-7 cmH(2)O impedance) or a sham ITD (0 cmH(2)O). Cerebral blood flow velocity (CBFV) was measured continuously via transcranial Doppler and analyzed in both time and frequency domains. Subjects were asked to report any subjective presyncopal symptoms (e.g., dizziness, nausea) at the conclusion of each LBNP exposure. Symptoms were coincident with physiological evidence of cardiovascular collapse (e.g., hypotension, bradycardia). Breathing on the active ITD increased LBNP tolerance time (mean +/- SE) from 2,014 +/- 106 s to 2,259 +/- 138 s (P = 0.006). We compared CBFV responses at the time of symptoms during the sham ITD trial with those at the same absolute time during the active ITD trial (when there were no symptoms). While there was no difference in mean CBFV at these time points (sham, 44 +/- 4 cm/s vs. active, 47 +/- 4; P = 0.587), total oscillations (sum of high- and low-frequency spectral power) of CBFV were higher (P = 0.004) with the active ITD (45.6 +/- 10.2 cm/s(2)) than the sham ITD (22.1 +/- 5.4 cm/s(2)). We conclude that greater oscillations around the same absolute level of mean CBFV are induced by inspiratory resistance and may contribute to the delay in symptoms and cardiovascular collapse that accompany progressive central hypovolemia.

Decreased phase shift between neck suction induced blood pressure and cerebral blood flow velocity oscillations indicates impaired cerebral autoregulation in type II diabetics

Decreased phase shift between neck suction induced blood pressure and cerebral blood flow velocity oscillations indicates impaired cerebral autoregulation in type II diabetics

Assessment of dynamic changes in cerebral autoregulation

Cerebral autoregulation (CA) is a control mechanism that adjusts cerebral vasomotor tone in response to changes in arterial blood pressure (ABP) to ensure a nearly constant cerebral blood flow. Patient treatment could be optimized if CA monitoring were possible. Whereas the concept of static CA assessment is simply based on comparison of mean values obtained from two stationary states (e.g., before and after a pressure change), the evaluation of dynamic CA is more complex. Among other methods, moving cross-correlation analysis of slow waves in ABP and cerebral blood flow velocity (CBFV) seems to be appropriate to monitor CA quasi-continuously. The calculation of an "instantaneous transfer function" between ABP and CBFV oscillations in the low-frequency band using the Wigner-Ville distribution may represent an acceptable compromise in time-frequency resolution for continuous CA monitoring.

Altered cerebral regulation in type 2 diabetic patients with cardiac autonomic neuropathy

Assessment of cerebral regulation in diabetic patients is often problematic because of the presence of cardiac autonomic neuropathy. We evaluated the technique of oscillatory neck suction at 0.1 Hz to quantify cerebral regulation in diabetic patients and healthy control subjects. In nine type 2 diabetic patients with cardiac autonomic neuropathy and 11 age-matched controls, we measured blood pressure and cerebral blood flow velocity responses to application of 0.1 Hz neck suction. We determined spectral powers and calculated the transfer function gain and phase shift between 0.1 Hz blood pressure and cerebral blood flow velocity oscillations as parameters of cerebral regulation. In the patients and control subjects, neck suction did not significantly influence mean values of the RR interval, blood pressure and cerebral blood flow velocity. The powers of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations increased in the control subjects, but remained stable in the patients. Transfer function gain remained stable in both groups. Phase shift decreased in the patients, but remained stable in control subjects. The absence of an increase in the power of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations confirmed autonomic neuropathy in the diabetic patients. Gain analysis did not show altered cerebral regulation. The decrease in phase shift in the patients indicates a more passive transmission of neck suction-induced blood pressure fluctuations onto the cerebrovascular circulation, i.e. altered cerebral regulation, in the patients, and is therefore suited to identifying subtle impairment of cerebral regulation in these patients.

Decreased phase shift between neck suction induced blood pressure and cerebral blood flow velocity oscillations indicates impaired cerebral autoregulation in type II diabetics

Decreased phase shift between neck suction induced blood pressure and cerebral blood flow velocity oscillations indicates impaired cerebral autoregulation in type II diabetics

Phase dynamics in cerebral autoregulation

Complex continuous wavelet transforms are used to study the dynamics of instantaneous phase difference delta phi between the fluctuations of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) in a middle cerebral artery. For healthy individuals, this phase difference changes slowly over time and has an almost uniform distribution for the very low-frequency (0.02-0.07 Hz) part of the spectrum. We quantify phase dynamics with the help of the synchronization index gamma = (sin delta phi)2 + (cos delta phi)2 that may vary between 0 (uniform distribution of phase differences, so the time series are statistically independent of one another) and 1 (phase locking of ABP and CBFV, so the former drives the latter). For healthy individuals, the group-averaged index gamma has two distinct peaks, one at 0.11 Hz [gamma = 0.59 +/- 0.09] and another at 0.33 Hz (gamma = 0.55 +/- 0.17). In the very low-frequency range (0.02-0.07 Hz), phase difference variability is an inherent property of an intact autoregulation system. Consequently, the average value of the synchronization parameter in this part of the spectrum is equal to 0.13 +/- 0.03. The phase difference variability sheds new light on the nature of cerebral hemodynamics, which so far has been predominantly characterized with the help of the high-pass filter model. In this intrinsically stationary approach, based on the transfer function formalism, the efficient autoregulation is associated with the positive phase shift between oscillations of CBFV and ABP. However, the method is applicable only in the part of the spectrum (0.1-0.3 Hz) where the coherence of these signals is high. We point out that synchrony analysis through the use of wavelet transforms is more general and allows us to study nonstationary aspects of cerebral hemodynamics in the very low-frequency range where the physiological significance of autoregulation is most strongly pronounced.

Dynamic Cerebral Autoregulation in Acute Ischemic Stroke Assessed From Spontaneous Blood Pressure Fluctuations

This study investigates dynamic cerebral autoregulation assessed from spontaneous blood pressure (ABP) and cerebral blood flow velocity (CBFV) fluctuations and its time course in acute ischemic stroke. Forty patients admitted with acute ischemic stroke in the territory of the middle cerebral artery (MCA) were enrolled. Admission National Institutes of Health Stroke score was 6+/-4. Study 1 was performed within 22 (+/-11) hours and study 2 was performed within 134 (+/-25) hours of ictus. The final analysis comprised 33 and 29 patients for study 1 and study 2, respectively. Twenty-five age- and sex-matched controls were studied. ABP (Finapres method) and CBFV in both MCAs (transcranial Doppler) were recorded over 10 minutes. Correlations between diastolic and mean ABP and CBFV fluctuations were averaged, yielding the correlation coefficient indices (Dx, Mx). Transfer function analysis was applied to obtain phase shift and gain between ABP and CBFV oscillations. No disturbance of autoregulation was indicated by all parameters at study 1. Separate analyses for clinical severity, stroke side, and size did not reveal significant differences for the various autoregulatory indices at study 1 and 2. At study 2, MCA flow velocity was significantly increased on both sides, the autoregulation index Mx was slightly but significantly (P<0.05) worse on both sides in comparison to study 1, and phase showed a trend toward poorer values on affected sides. No significant differences to controls occurred. Clinical outcome in patients completing both studies was good in all but one patient. Dynamic cerebral autoregulation assessed from spontaneous blood pressure fluctuations does not seem to be relevantly disturbed in early minor MCA stroke. At the subacute stage, slight autoregulatory disturbance may be present.

Dynamic cerebral autoregulation is impaired in glaucoma

Objectives: Autonomic and endothelial dysfunction is likely to contribute to the pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma (POAG). Although there is evidence of vasomotor dysregulation with decreased peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been evaluated. The aim of our study was to assess dynamic CA in patients with NPG and POAG. Materials and Methods: In 10 NPG patients, 11 POAG patients and 11 controls, we assessed the response of cerebral blood flow velocity (CBFV) to oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz. CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz oscillations in MAP and CBFV. Results: 0.1 Hz spectral powers of MAP did not differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients with NPG (5.68±1.2 cm 2 s −2) and POAG (6.79±2.1 cm 2 s −2) than in controls (2.40±0.4 cm 2 s −2). Furthermore, the MAP–CBFV gain was higher in NPG (2.44±0.5 arbitrary units [a.u.]) and POAG (1.99±0.2 a.u.) than in controls (1.21±0.1 a.u.). Conclusion: Enhanced transmission of oscillations in MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and might contribute to an increased risk of cerebrovascular disorders in these diseases.

Impaired dynamic cerebral autoregulation in eclampsia

Eclampsia is frequently associated with brain edema, cerebral infarction or hemorrhage. Its underlying cerebrovascular pathophysiology is still poorly understood. We examined cerebral autoregulation by a non-invasive multimodal assessment in a 28-year-old primaparous woman with postpartal eclampsia. Transcranial Doppler sonography showed considerably increased cerebral blood flow velocity (CBFV) of all basal cerebral vessels. Magnetic resonance imaging demonstrated multifocal vasogenic brain edema. Using transfer function analysis, a severely decreased phase shift between respiratory-induced 0.1-Hz oscillations of arterial blood pressure and CBFV was observed, indicating substantial disturbance of dynamic cerebral autoregulation (DCA). In contrast, CO(2)-vasomotor reactivity of the right middle cerebral artery was only slightly reduced. We therefore assume that the cerebral arteriolar dysfunction in eclampsia leads primarily to an impairment of the autoregulatory mechanism that is followed by different degrees of arteriolar vasodilation. Because of its probably high sensitivity to hemodynamic disturbances, assessment of DCA might be of great value in early pre-eclampsia for risk prediction of cerebral arteriopathy and eclampsia.

Spontaneous fluctuations in cerebral blood flow: insights from extended-duration recordings in humans.

To determine the dependence of cerebral blood flow (CBF) on arterial pressure over prolonged time periods, we measured beat-to-beat changes in mean CBF velocity in the middle cerebral artery (transcranial Doppler) and mean arterial pressure (Finapres) continuously for 2 h in six healthy subjects (5 men and 1 woman, 18-40 yr old) during supine rest. Fluctuations in velocity and pressure were quantified by the range [(peak - trough)/mean] and coefficients of variation (SD/mean) in the time domain and by spectral analysis in the frequency domain. Mean velocity and pressure over the 2-h recordings were 60 +/- 7 cm/s and 83 +/- 8 mmHg, associated with ranges of 77 +/- 8 and 89 +/- 10% and coefficients of variation of 9.3 +/- 2.2 and 7.9 +/- 2.3%, respectively. Spectral power of the velocity and pressure was predominantly distributed in the frequency range of 0.00014-0.1 Hz and increased inversely with frequency, indicating characteristics of an inverse power law (1/f(alpha)). However, linear regression on a log-log scale revealed that the slope of spectral power of pressure and velocity was steeper in the high-frequency (0.02-0.5 Hz) than in the low-frequency range (0.002-0.02 Hz), suggesting different regulatory mechanisms in these two frequency ranges. Furthermore, the spectral slope of pressure was significantly steeper than that of velocity in the low-frequency range, consistent with the low transfer function gain and low coherence estimated at these frequencies. We conclude that 1) long-term fluctuations in CBF velocity are prominent and similar to those observed in arterial pressure, 2) spectral power of CBF velocity reveals characteristics of 1/f(alpha), and 3) cerebral attenuation of oscillations in CBF velocity in response to changes in pressure may be more effective at low than that at high frequencies, emphasizing the frequency dependence of cerebral autoregulation.

Cerebrovascular mechanisms in neurocardiogenic syncope with and without postural tachycardia syndrome

Background and purpose: Recent transcranial Doppler studies in patients with neurocardiogenic syncopes (NCS) have demonstrated that the cerebrovascular response to sudden systemic hypotension is vasoconstriction instead of compensatory vasodilation (autoregulation). We tried to characterize the conditions leading to this unexpected response in NCS patients further by continuously monitoring autoregulation and autonomic parameters during a standardized tilt-table test (TTT). Methods: Sixteen patients below the age of 50 years with a history of at least three syncopes of undetermined cause and tilt-table verified NCS and 20 normal controls were studied. Arterial blood pressure (ABP) and heart rate (HR) were monitored by Finapres and cerebral blood flow velocity (CBFV) of the left middle cerebral artery by transcranial Doppler. Baroreflex sensitivity and autoregulation parameters were measured continuously, using cross-spectral analysis of Mayer waves (3–9 cycles per minute oscillations) in ABP, HR and CBFV, respectively. Pulsatility indices (PI) of CBFV and ABP were determined continuously. Measurements were taken during 5 min in supine and during 5 min in tilted position. In patients, tilting was continued for a maximum of 45 min until the onset of syncope or presyncope. Results: According to the maximum increase in heart rate (ΔHR) during the first 5 min of standing, heart rate responses were classified as postural tachycardia syndrome (POTS) (ΔHR>35/min) or as normal. Only one out of 20 control subjects showed a POTS (5%) in contrast to seven patients (44%). Patients with a POTS had significantly lower PI values in ABP and higher ratios between the PI of CBFV and the PI of ABP both in supine and in tilted positions. Baroreflex sensitivity during standing decreased significantly in POTS patients when compared to controls. Although autoregulation remained intact during standing, mean CBFV decreased significantly and continuously. The nine patients without a POTS showed almost the same cardiovascular and cerebrovascular responses as the control subjects. All 16 patients showed similar circulatory responses during syncope (sudden hypotension, relative or absolute bradycardia, reduced CBFV and increased PI in CBFV). Conclusions: The development of a POTS during tilting indicates a high risk for fainting. The characteristic hemodynamic features in the initial phase of standing in these patients can be interpreted in terms of central hypovolemia (low PI of ABP) with sufficient ABP regulation and increased cerebrovascular resistance (defined as the ratio between PI of CBFV and ABP). Cerebral autoregulation seems not to be affected in patients suffering from NCS.

Cross-spectral analysis of cerebral autoregulation dynamics in high risk preterm infants during the perinatal period.

In preterm infants intraventricular hemorrhage occurs predominantly within the perinatal period, which may be due to a "lost autoregulation" of cerebral blood flow (CBF). In this study, perinatal autoregulation dynamics were investigated in high risk preterm infants by cross-spectral analysis (CSA), which is a statistical tool in the analysis of time series. In 15 ventilated preterm infants of 25-32 gestational weeks, a total number of 30 records were made between 24 and 96 h of life. Doppler-derived CBF velocity (CBFv), used as a quantitative measure for CBF, and direct mean arterial blood pressure (MABP) were measured continuously for 10 min. The spectral power of low frequency (LF, 0.02-0.2 Hz) oscillations in CBFv and MABP was quantified by spectral analysis. From the results of CSA, a LF phase-shift between the CBFv and MABP LF oscillations was calculated in each record. Within the study group, the LF spectral power of CBFv and MABP was initially low and increased significantly until 96 h of life. The LF phase-shift was about 0 degrees at 24 h and increased significantly to 55 degrees at 96 h of life. The initially low LF spectral power of CBFv and MABP may indicate a perinatal depression of autonomic nervous centers, which are thought to control LF oscillations of vital parameters. In the light of a high pass filter model for autoregulation, the initially low LF phase-shift may indicate an initially impaired autoregulation, which supports the "lost autoregulation" hypothesis.

Phase relationship between cerebral blood flow velocity and blood pressure. A clinical test of autoregulation.

This study investigates the usefulness, as a test of dynamic autoregulation, of phase shift angle analysis between oscillations in cerebral blood flow velocity (CBFV) and in arterial blood pressure (ABP) during deep breathing. Fifty healthy volunteers, 20 patients with occlusive cerebrovascular diseases (OCD), and 10 patients with arteriovenous malformations (AVM) took part in the study. All subjects received transcranial Doppler monitoring of both middle cerebral arteries (MCAs). In addition, continuous blood pressure monitoring was performed with the use of noninvasive servo-controlled infrared finger plethysmography during deep breathing at a rate of 6/min. With the use of a high-pass filter model of autoregulation, autoregulation was quantified as phase shift angle between oscillations in CBFV and ABP at a frequency of 6/min. A phase shift angle of 0 degrees indicates total absence of autoregulation, while 90 degrees can be gauged as optimal autoregulation. In addition, vasomotor reactivity of both MCAs to CO2 stimulation was assessed among patients and calculated as percent increase in CBFV per millimeter of mercury of increase in CO2. All normal subjects showed positive phase shift angles between CBFV and ABP (mean +/- SD, 70.5 +/- 29.8 degrees). OCD patients presented with significantly decreased phase shift angles for the MCA only on the pathological side (51.7 +/- 35.1 degrees; P < .05). Patients with AVM showed significantly reduced phase shift angles on both the affected side (26.8 +/- 13.5 degrees; P < .001) and the unaffected side (40.6 +/- 26.6 degrees; P < .01). In patients' groups, phase shift angle and vasomotor reactivity correlated significantly (r = .66; P < .001) after results from all MCAs were pooled. Results confirm the high-pass filter model of cerebral autoregulation: Normal subjects showed predicted positive phase shift angles between CBFV and ABP oscillations. Patients with expected autoregulatory disturbances showed significant decreases in phase shift angles. Close correlations existed between autoregulation and CO2-induced vasomotor reactivity.

Cerebral autoregulation of preterm neonates--a non-linear control system?

The low frequency cerebral blood flow velocity (CBFV) oscillations in neonates are commonly attributed to an under-dampened immature linear type cerebral autoregulation, and the 'instability' is regarded as causative for peri-intraventricular haemorrhage/periventricular leukomalacia. In contrast, oscillations susceptible to frequency entrainment are a fundamental part of the stable function of non-linear control systems. To classify the autoregulation an observational study was done on the relationship between CBFV oscillations, heart rate variability, and artificial ventilation. In 10 preterm neonates (gestational age 26 to 35 weeks) we serially Doppler traced arterial CBFV continuously for 12 minutes between days 1 and 49 of life. The individual time series of CBFV and heart rate were subjected to spectral analysis. Forty six of 47 tracings showed significant low frequency CBFV oscillations. Low frequency heart rate oscillations were not a prerequisite thereof. All patients with < 30% of total power in the low frequency band of CBFV oscillations were on the ventilator. Three of them demonstrated a shift of spectral power from low frequency to a frequency equal or harmonic to the ventilator rate indicating entrainment. The findings of CBFV oscillations combined with entrainment classify the autoregulation as a non-linear system. It is suggested that entrainment by periodic high amplitude stimuli might challenge the regulatory capacity to its limits thus increasing the risk for cerebral damage.

CEREBRAL AUTOREGULATION IS A NONLINEAR TYPE CONTROL SYSTEM

Introduction. In neonates, low frequency (LF) cerebral blood flow velocity oscillations (CBFV-O) are commonly attributed to an underdampened immature cerebral autoregulation (AR). Peri-intraventricular hemorrhage (PIVH) is linked to this ‘instability’. In contrast to linear type control systems, nonlinear type systems express a regular periodicity as a fundamental part of their stable function. Aims. To classify the AR, and to identify factors possibly responsible for PIVF by investigating the relationship between CBFV-O, heart rate variability (HR-V), and intermittent positive pressure ventilation (IPPV). Methods. In 5 preterm neonates (GA 26 to 30 w) we serially Doppler-traced arterial CBFV continuously for 12 min every 3 to 7 days between days 1 and 49 of life. Another 5 preterms (GA 26 to 35 w) were traced sporadically. The time series of both CBFV and HR were subjected to spectral analysis. Results. 46/47 tracings showed LF CBFV-0 (p<0.0001, one sample z-test). For HR, cycling was observed in only 15/47 tracings. LF cycling in HR was not a prerequisite for LF CBFV-O. All patients with < 30 % of total power in the LF band of CBFV-O were on the ventilator. Three of these patients demonstrated a shift of spectral power from LF to a frequency equal or harmonic to the ventilator rate in the sense of entrainment. The range of entrainment encompassed 12 to 25/min stimuli. Conclusion. In analogy to thermo- and blood pressure regulation, CBFVO and entrainment classify the AR as a nonlinear system. HR-V has no direct impact on CBFV-O, whereas respiration acts on both HR-V and CBFV-O. We discuss that periodic high-amplitude stimuli (i.e. IPPV in RDS) may challenge the regulatory capacity of the CBF control system as reflected by entrainment. While fragile vascular matrix elements, severe central blood pressure changes, and high pCO2 are prerequisites, entrainment of CBFV-O might be one key event for cerebral damage.

Spontaneous oscillations in cerebral blood flow velocity in normal humans and in patients with carotid artery disease

Spontaneous oscillations in cerebral blood flow velocity (CBFV) in normals and in patients with stenoses or occlusions of the internal cerebral artery were measured using transcranial Doppler sonography. In normal subjects, large oscillations of up to ±30% from the mean CBFV were found with low frequencies between 0.4 and 9 cycles/min. No correlations between CBFV oscillations and systemic circulatory parameters were detected. In patients with carotid artery obstructions the CBFV oscillations were significantly reduced in the middle cerebral artery ipsilaterally to a hemodynamically significant lesion, but not contralaterally. Our results support the hypothesis that spontaneous oscillations (B-waves) of small pial vessels are responsible for the CBFV fluctuations.