Spontaneous oscillations of arterial blood pressure,cerebral and peripheral blood flow in healthy and comatose subjects

Abstract

Slow and rhythmic spontaneous oscillations of cerebral and peripheral blood flow occur within frequencies of 0.5-3 min~1 (0.008-0.05 Hz, B-waves) and 3-9 min~1 (0.05-0.15 Hz, M-waves). The generators and pathways of such oscillations are not fully understood. We compared the coefficient of variance (CoV), which serves as an indicator for the amplitude of oscillations and is calculated as the percent standard deviation of oscillations within a particular frequency band from the mean, to study the impairment of generators or pathways of such oscillations in normal subjects and comatose patients in a controlled fashion. With local ethic committee approval, data were collected from 19 healthy volunteers and nine comatose patients suffering from severe traumatic brain injury (n = 3), severe subarachnoid hemorrhage (n = 3), and intracerebral hemorrhage (n = 3). Cerebral blood flow velocities were measured by transcranial Doppler ultrasound (TCD), peripheral vasomotion by finger tip laser Doppler flowmetry (LDF), and ABP by either non-invasive continuous blood pressure recordings (Finapres method) in control subjects, or by direct radial artery recordings in comatose patients. Each recording session lasted ~ 20-30 min. Data were stored in the TCD device for offline analysis of CoV. For CoV in the cerebral B-wave frequency range there was no difference between coma patients and controls, however there was a highly significant reduction in the amplitude of peripheral B-wave LDF and ABP vasomotion (3.8 ±2.1 vs. 28.2 ± 76.7 for LDF, p < 0.00 7; and 1.2±0.7 vs. 4.6±2.8 for ABP, p < 0.001) This observation was confirmed for spontaneous cerebral and peripheral oscillations in the M-wave frequency range. The CoV reduction in peripheral LDF and ABP oscillations suggest a severe impairment of the proposed sympathetic pathway in comatose patients. The preservation of central TCD oscillations argues in favor of different pathways and/or generators of cerebral and peripheral B- and M-waves. [Neurol Res 1999; 21: 665-669]     

Spontaneous blood pressure oscillations and cerebral autoregulation

The relationship between spontaneous oscillations in cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP) was analysed in normal subjects in order to evaluate whether these relationships provide information about cerebral autoregulation. CBFV was measured using transcranial Doppler sonography and continuous ABP and heart rate using Finapres in 50 volunteers. Measurements were made over 5 min in a supine position and 6 min in a tilted position. Coefficients of variation were calculated using power- and cross-spectral analysis in order to quantify amplitudes within two frequency ranges: 3–9 cycles per min (cpm) (M-waves); and 9–20 cpm (R-waves). Correlations, coherence values, phase angle shifts and gains were also computed between corresponding waves in CBFV and in ABP. A clear correlation was seen for M-waves and R-waves between CBFV and ABP and coherence values were large enough to calculate phase angle shifts and gains. Phase angles for M-waves were larger and gains lower than was the case for R-waves, either tilted or supine. These data are consistent with a highpass filter model of cerebral autoregulation. Relatively high CBFV/ABP gain values (between 1.4 and 2.0) suggest that the principle of frequency-dependent vascular input impedances has to be considered in addition to autoregulatory feedback mechanisms. Spontaneous ABP oscillations in the M-wave and R-wave ranges may serve as a basis for continuous autoregulation monitoring.     

Mechanisms underlying phase lag between systemic arterial blood pressure and cerebral blood flow velocity

To explore the mechanisms underlying the phase lag between oscillations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV), ABP and CBFV signals were recorded noninvasively from normal volunteers who lay quietly in a supine position. Mean ABP (MAP) and CBFV (MFV) were calculated beat-to-beat by means of integration. Cerebral vascular resistance (CVR) was calculated by dividing MAP with MFV. Frequency domain analysis of MAP, MFV and CVR signals revealed very-low frequency (VLF, 0.016-0.04 Hz), low-frequency (LF, 0.04-0.15 Hz), and high-frequency (HF, 0.15-0.4 Hz) components. The transfer phase of MAP-CVR coupling in the LF and HF range was frequency-dependent, which is equivalent to a time delay of 2 s. However, the transfer phase differed in the CVR-MFV coupling in that the phase was distributed around 180 degrees across the LF and HF ranges. Cross-correlation analysis revealed a positive relationship between MAP-CVR coupling, with MAP leading by 2 s, and a negative relationship between CVR-MFV coupling, with CVR leading by 0.3 s. We concluded that the phase lag between oscillations in ABP and CBFV was chiefly contributed to by the starting latency of cerebral autoregulation (i.e. cerebral vasomotion, revealed by MAP-CVR coupling). Moreover, the negative correlation of the CVR-MFV coupling could offer a different explanation for the physiologic significance of the phase lead of CBFV-ABP oscillations.     

Predictability of intracranial pressure oscillations in patients with suspected normal pressure hydrocephalus by transcranial Doppler ultrasound

Abstract

Intracranial pressure (ICP) was monitored continuously for one night in 36 patients with suspected symptomatic normal pressure hydrocephalus (NPH) to identify patients who might benefit from subsequent shunting. In 33 of these patients middle cerebral artery (MCA) blood flow velocity by means of transcranial Doppler sonography (TCD) and ICP were recorded simultaneously. ICP B-waves always paralleled changes in the TCD signal (TCD B-wave equivalents). The relative frequency of ICP B-waves was predictable by TCD, albeit slightly underestimated due to a generally lower relative amplitude of the TCD B-wave equivalents. However; the same TCD B-wave equivalent amplitude could be accompanied by quite different ICP changes in different patients. Considering the baseline values in the absence of pressure wavesthere was no significant relationship between ICP and TCD resistance index (Pourcelot) in different patients. Raising ICP by injection of 10 ml saline into the ventricle, however was accompanied by an increased TCD resistance index in the individual patient. As the relative frequency of B-wave activity is assumed to be an indicator for shunt responsiveness, continuous TCD monitoring can be used as a screening procedure to detect the presence and the relative frequency of B-wave activity in patients with suspected NPH. However, since neither the absolute ICP nor the amplitude of spontaneous oscillations can be predicted, TCD monitoring is not suitable to replace ICP monitoring. [Neurol Res 1994; 16: 398-402]     

M-wave analysis and passive tilt in patients with different degrees of carotid artery disease

BACKGROUND AND PURPOSE: Carotid artery disease (CAD) is able to critically impair cerebral autoregulation which increases the risk for stroke. As therapeutic strategy largely depends on the degree of CAD, we investigated whether this gradation is also related to significant changes in autoregulatory capacity. We applied cross-spectral analysis (CSA) of spontaneous Mayer-wave (M-wave) oscillations and passive tilting (PT) to test cerebral autoregulation. METHODS: Cerebral autoregulation was tested in 102 patients with carotid stenosis (> or =70%) or occlusion and 14 controls by comparison of continuous transcranial Doppler sonography of the middle cerebral artery and beat-to-beat arterial blood pressure (ABP) during PT to 80 degrees head-up position as well as by CSA of M-waves (3-9 cpm). RESULTS: The orthostatic decrease of cerebral blood flow velocity (CBFV) was not correlated with the degree of CAD and showed a lower sensitivity and specificity than phase angle shifts between M-waves in ABP and CBFV (sensitivity: 75-80%, specificity: 86%). Phase angles were gradually lowered in carotid stenoses > 70%, but apparently, they were only moderately correlated with the degree of CAD (r = -0.35, P < 0.01). An additional influencing factor seemed to be the sufficiency of collateralization. CONCLUSIONS: The results show that CSA of M-waves is more appropriate for testing autoregulation than PT. CSA suggests that the capacity to autoregulate depends to a certain extent on the degree of CAD but is also influenced by the sufficiency of collateral pathways and pre-existing strokes.     

Chemical stimulation of the rostral ventrolateral medullary pressor area decreases cerebral blood flow in anesthetized rats.

In urethane-anesthetized, paralyzed and artificially ventilated rats, the neurons in the rostral ventrolateral medullary pressor area (VLPA) were chemically stimulated by microinjections of L-glutamate (1.7-5.0 nmole in 100 nl of 0.9% sodium chloride solution) and the cerebral blood flow (CBF) was determined using a combination of labeled microspheres (57Co, 113Sn and 46Sc). In one group of rats (n = 11), unilateral chemical stimulation of the VLPA produced a significant (P less than 0.01) increase in arterial blood pressure (ABP), a significant (P less than 0.05) decrease in CBF, and a significant (P less than 0.01) increase in cerebrovascular resistance (CVR) in the cerebral cortex ipsilateral to the stimulated VLPA. The CBF was 52 +/- 3 (mean +/- S.E.M.) and 48 +/- 4 ml.min-1.(100 g)-1 before and during the chemical stimulation of VLPA; the CVR was 1.9 +/- 0.1 and 2.6 +/- 0.3 mmHg per ml.min-1.(100 g)-1 before and during the stimulation. In order to measure CBF at normotension, moderate hypotension was induced by controlled hemorrhage in another group of rats (n = 8). Unilateral chemical stimulation of the VLPA in these rats increased ABP but it remained within normotensive range. The CBFs of ipsilateral and contralateral cerebral cortices decreased significantly (P less than 0.05) from 57 +/- 14 to 41 +/- 9 and from 50 +/- 12 to 39 +/- 9 ml.min-1.(100 g)-1, respectively. The CVRs of ipsilateral and contralateral cortices increased significantly (P less than 0.05) from 2.6 +/- 0.6 to 3.5 +/- 0.8 and from 2.7 +/- 0.5 to 3.5 +/- 0.8 mmHg/[ml.min-1.(100 g)-1], respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chemical stimulation of the nucleus tractus solitarii decreases cerebral blood flow in anesthetized rats

In anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, the neurons in the nucleus tractus solitarius (NTS) were chemically stimulated by microinjections of L-glutamate and the cerebral blood flow (CBF) was determined using a combination of labeled microspheres (either 57Co, 113Sn and 46Sc or 141Ce, 85Sr and 46Sc). Unilateral chemical stimulation of the NTS (n = 14) decreased CBF significantly in most brain areas. The decrease in CBF was not due to the decrease in arterial blood pressure (ABP) because the CBF of the whole cerebral cortex during the chemical stimulation of the NTS was significantly smaller (P less than 0.05) than the CBF during controlled hemorrhagic hypotension (n = 10). In another group of rats (n = 6), moderate hypertension was induced by blood transfusion. Unilateral chemical stimulation of the NTS in these rats decreased ABP but it remained within normotensive range. A significant (P less than 0.05) decrease in CBF (from 62 +/- 28 (mean +/- S.D.) to 48 +/- 23 ml.min-1.(100 g)-1) and increase in cerebrovascular resistance (from 1.9 +/- 1.2 to 2.6 +/- 1.2 mm Hg per [ml.min-1.(100 g)-1]) was observed in the whole cerebral cortex of these rats. Chemical stimulation of the NTS did not affect the reactivity of the cerebral vessels to hypercapnea (n = 5). These results suggest that the cell bodies within the NTS may play a role in the control of cerebral circulation.     

Chemical stimulation of the ventrolateral medullary depressor area decreases ipsilateral cerebral blood flow in anesthetized rats.

In anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, the neurons in the ventrolateral medullary depressor area (VLDA) were chemically stimulated by microinjections of L-glutamate (2.5-5 nmole in 100 nl of 0.9% sodium chloride solution) and the cerebral blood flow (CBF) was determined using a combination of labeled microspheres (57Co, 113Sn and 46Sc). Unilateral chemical stimulation of the VLDA (n = 11) produced a significant (P less than 0.05) decrease in CBF of the cerebral cortex ipsilateral to the stimulated VLDA; the CBF was 41 +/- 5 (mean +/- S.E.M.) and 29 +/- 4 ml.min-1.(100 g)-1 before and during the chemical stimulation of VLDA. The decrease in CBF was not due to the decrease in arterial blood pressure (ABP) caused by the chemical stimulation of the VLDA because the CBF during the chemical stimulation of the VLDA was significantly smaller (P less than 0.01) than the CBF during controlled hemorrhagic hypotension (n = 10). In another group of rats (n = 6), moderate hypertension was induced by blood transfusion. Unilateral chemical stimulation of the VLDA in these rats decreased ABP but it remained within normotensive range. A significant (P less than 0.05) decrease in CBF (from 46 +/- 12 to 29 +/- 7 ml.min-1.(100 g)-1) and a significant (P less than 0.01) increase in cerebrovascular resistance (from 2.7 +/- 0.4 to 4.3 +/- 0.6 mmHg per [ml.min-1.(100 g)-1]) was observed in the ipsilateral cerebral cortex of these rats. Chemical stimulation of the VLDA did not affect the reactivity of the cerebral vessels to hypercapnea (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Slow oscillations in middle cerebral artery cerebral blood flow velocity and aging

OBJECTIVE: A recent study using near infrared spectroscopy (NIRS) showed that low frequency oscillations of regional cerebral blood flow (CBF) decline with age. Using transcranial Doppler ultrasound (TCD), it is possible to monitor similar fluctuations in cerebral blood velocity (CBV) in basal cerebral vessels. Such oscillations have been used widely in the assessment of cerebral autoregulation. We postulated that it should be possible to observe similar age related reductions in the amplitude of slow waves recorded using TCD. METHODS: We studied 187 patients with head injury, who were admitted to Addenbrooke's Neuro Critical Care unit between 1992 and 1998. Intermittent recordings of CBV were undertaken using TCD, which were subsequently analysed using software developed in-house. Power spectra were computed in the very low frequency (VLF: 0.01-0.05 Hz) and low frequency (LF: 0.07-0.11 Hz) ranges for all signals and a regression analysis was performed to assess the correlation between power in each frequency band and age. RESULTS: No significant correlation was found between VLF or LF power and age (VLF: r=0.037; p=0.63; LF: r=-0.05, p=0.517). DISCUSSION: While remaining cogniscent of the complex nature of our patient group, we find that age dependent reductions in CBF oscillations seen using NIRS do not translate to recordings of CBV in the middle cerebral artery in patients with head injury.     

Rhythmic oscillations with a wavelength of 0.5–2 min in transcranial Doppler recordings

We have studied intracranial pressure (ICP) B-waves and their association with rhythmic changes in blood flow velocity (B-wave equivalents) by transcranial Doppler sonography (TCD) monitoring. In overnight TCD recordings in 10 normal young adults, these rhythmic changes in blood flow velocity were higher and more frequent during REM sleep and sleep stage 1 than during other sleep stages. B-wave equivalents also had a longer wavelength during REM sleep. Their relative frequency in these normal subjects over one night ranged from 35 to 73%. Peripheral resistance (assessed by the Pourcelot index) was lower and heart rate was higher at the peak of these oscillations. These results support the hypothesis that ICP B-waves are caused by vasodilation. A non-linear relationship between ICP and blood flow velocity was found during B-waves in 9 of 11 patients with suspected NPH. Our results throw doubt on the suggestion that a relative frequency of less than 80% B-wave activity can be a valid indicator for shunt responsiveness in patients with suspected normal pressure hydrocephalus (NPH). ICP recordings in suspected NPH should be accompanied by polysomnography to avoid misleading results due to variability of B-wave appearance dependant on sleep pattern.     

Predominant endothelial vasomotor activity during human sleep: a near‐infrared spectroscopy study

Vasomotion is important in the study of vascular disorders, including stroke. Spontaneous low and very low hemodynamic oscillations (3–150 mHz) measured with near‐infrared spectroscopy (NIRS) reflect the endothelial (3–20 mHz), neurogenic (20–40 mHz) and myogenic (40–150 mHz) components of vasomotion. We investigated sleep‐specific patterns of vasomotion by characterizing hemodynamic oscillations with NIRS in healthy subjects, and tested the feasibility of NIRS as a bedside tool for monitoring vasomotion during whole‐night sleep. To characterize local cerebral vasomotion, we compared cerebral NIRS measurements with muscular NIRS measurements and peripheral arterial oxygen saturation (SpO₂) during different sleep stages in 14 healthy volunteers. Spectral powers of hemodynamic oscillations in the frequency range of endothelial vasomotion were systemically predominant in every sleep stage, and the powers of endothelial and neurogenic vasomotion decreased in deep sleep as compared with light sleep and rapid eye movement (REM) sleep in brain, muscle, and SpO₂. The decrease in the powers of myogenic vasomotion in deep sleep only occurred in brain, and not in muscle. These results point to a predominant role of endothelial function in regulating vasomotion during sleep. The decline in cerebral endothelial and neurogenic vasomotion during progression to deeper non‐REM sleep suggests that deep sleep may play a protective role for vascular function. NIRS can be used to monitor endothelial control of vasomotion during nocturnal sleep, thus providing a promising non‐invasive bedside tool with which to study the sleep‐relevant pathological mechanisms in vascular diseases and stroke.     

CBF and transcranial Doppler sonography during vasodilatory stress tests in patients with common carotid artery occlusion.

Cerebral blood flow (CBF) and the cerebral vasoreactivity was measured in patients with cerebrovascular disease and longstanding occlusion of the common carotid artery (CCA). In addition, regional CBF was correlated with transcranial doppler (TCD) measurements at baseline and during 6% CO2 inhalation and after intravenous administration of 1 g of acetazolamide. Twelve patients with a mean age of 62 years (range 45 to 71 years) were included, and the data compared to age-matched healthy controls. CBF was measured by intravenous injection of xenon-133 and SPECT (Tomomatic 564). TCD of the middle cerebral artery (MCA) was done by EME TC-64B. A very low global CBF value of 28 +/- 5 (SD) ml 100 g-1 min-1 was found at baseline as compared to 55 +/- 5 ml 100 g-1 min-1 in the normal controls. During 6% CO2-inhalation and after acetazolamide administration, CBF increased by 58 +/- 24% and 51 +/- 21%, respectively, indicating substantial collateral supply. Correlative analysis of CBF in the MCA territory and TCD in the MCA showed statistical significance only for the pooled data, i.e. compiling the data obtained during baseline and the two vasodilatory tests, and then only for the mean and peak TCD velocity (e.g. r = 0.59, p less than 0.002, n = 35, mean velocity, right side). We conclude that TCD measurements do not predict regional CBF in patients with CCA occlusion. The study emphasizes that these two methods yield supplementary information, with TCD measurements providing information of the circle of Willis and CBF studies of the flow distribution.     

Simultaneous recording of cerebrospinal fluid pressure and middle cerebral artery blood flow velocity in patients with suspected symptomatic normal pressure hydrocephalus.

CSF pressure (intracranial pressure, in one patient lumbar pressure) was monitored continuously for one night in 23 patients with suspected symptomatic normal pressure hydrocephalus (NPH) to identify patients who might benefit from subsequent shunt surgery. In 20 patients middle cerebral artery (MCA) blood flow velocity by means of transcranial Doppler sonography (TCD) and CSF pressure were recorded simultaneously. In three patients transcranial Doppler signals were insufficient. Spontaneous changes in CSF pressure always paralleled changes in the TCD signal. Equivalents of B-waves as well as intermediate waves (in between B- and A-waves), and C-waves could be identified easily and always appeared in phase. The Doppler signal, however, could not be used to evaluate the absolute changes in CSF pressure. Fast Fourier Transform of the Doppler signal was a useful tool to indicate the relative frequency of B-wave equivalents. In five patients the injection of 10ml saline into the ventricle raised intracranial pressure considerably, but hardly affected the MCA blood flow velocity. Continuous TCD monitoring might be useful as a noninvasive screening procedure in patients with suspected symptomatic NPH before continuous invasive CSF pressure measurements are performed.     

Variability and fractal analysis of middle cerebral artery blood flow velocity and arterial blood pressure in subarachnoid hemorrhage.

Higher biologic systems operate far from equilibrium resulting in order, complexity, fluctuation of inherent parameters, and dissipation of energy. According to the decomplexification theory, disease is characterized by a loss of system complexity. We analyzed such complexity in patients after subarachnoid hemorrhage (SAH), by applying the standard technique of variability analysis and the novel method of fractal analysis to middle cerebral artery blood flow velocity (FV) and arterial blood pressure (ABP). In 31 SAH -patients, FV (using transcranial Doppler sonography) and direct ABP were measured. The standard deviations (s.d.) and coefficients of variation (CV=relative s.d.) for FV and ABP time series of length 2(10) secs were calculated as measures of variability. The spectral index beta(low) and the Hurst coefficient H(bdSWV) were analyzed as fractal measures. Outcome was assessed 1 year after SAH according to the Glasgow Outcome Scale (GOS). Both FV (beta(low)=2.2+/-0.4, mean+/-s.d.) and ABP (beta(low)=2.3+/-0.4) were classified as nonstationary (fractal Brownian motion) signals. FV showed significantly (P<0.05) higher variability (CV=7.2+/-2.5%) and Hurst coefficient (H(bdSWV)=0.26+/-0.13) as compared with ABP (CV=5.5+/-2.7%, H(bdSWV)=0.19+/-0.11). Better outcome (GOS) correlated significantly (P<0.05) with higher s.d. of FV (Spearman's r(s)=0.51, r(s)(2)=0.26) and ABP (r(s)=0.57, r(s)(2)=0.32), as well as with a higher Hurst coefficient of ABP (r(s)=0.46, r(s)(2)=0.21). Cerebral vasospasm reduced CV of FV, but left H(bdSWV) unchanged. FV and ABP fluctuated markedly despite homeostatic control. A reduced variability of FV and ABP might indicate a loss of complexity and was associated with a less favorable outcome. Therefore, the decomplexification theory of illness may apply to SAH.     

Cerebral autoregulation and ageing.

Little is known about the effects of ageing on cerebral autoregulation (CA). To examine the relationship between age and CA in adults, we conducted a prospective study using a non-invasive protocol without external stimuli. We studied 32 subjects, aged 23-68 years. They were assigned to a young group (28+/-5 years) and an old group (54+/-8 years). The groups were sex-matched. Transcranial Doppler ultrasonography (TCD) was used to record bilateral middle cerebral artery flow velocities (CBFV, cm/sec). Noninvasive beat-to-beat tonometric arterial blood pressure (ABP) measurement of the radial artery was used to record spontaneous blood pressure fluctuations. The Mx, an index of dynamic cerebral autoregulation (dCA), was calculated from a moving correlation between ABP and CBFV. We did not find a correlation between age and Mx. No statistically significant difference in the Mx between the groups (0.27+/-0.23, young, vs. 0.37+/-0.24, old) was demonstrated. Age does not affect dynamic cerebral autoregulation assessed by the Mx index in healthy adult subjects. This study supports findings from previous papers wherein CA was measured with protocols which require external stimuli. Further studies are needed to determine CA in subjects above 70 years of age.     

Intersubject variability and reproducibility of 15O PET studies.

Oxygen-15 positron emission tomography (15O PET) can provide important data regarding patients with head injury. We provide reference data on intersubject variability and reproducibility of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolism (CMRO2) and oxygen extraction fraction (OEF) in patients and healthy controls, and explored alternative ways of assessing reproducibility within the context of a single PET study. In addition, we used independent measurements of CBF and CMRO2 to investigate the effect of mathematical correlation on the relationship between flow and metabolism. In patients, intersubject coefficients of variation (CoV) for CBF, CMRO2 and OEF were larger than in controls (32.9%+/-2.2%, 23.2%+/-2.0% and 22.5%+/-3.4% versus 13.5%+/-1.4%, 12.8%+/-1.1% and 7.3%+/-1.2%), while CoV for CBV were lower (15.2%+/-2.1% versus 22.5%+/-2.8%) (P<0.001). The CoV for the test-retest reproducibility of CBF, CBV, CMRO2 and OEF in patients were 2.1%+/-1.5%, 3.8%+/-3.0%, 3.7%+/-3.0% and 4.6%+/-3.5%, respectively. These were much lower than the intersubject CoV figures, and were similar to alternative measures of reproducibility obtained by fractionating data from a single study. The physiological relationship between flow and metabolism was preserved even when mathematically independent measures were used for analysis. These data provide a context for the design and interpretation of interventional PET studies. While ideally each centre should develop its own bank of such data, the figures provided will allow initial generic approximations of sample size for such studies.     

Quantitative measurement of cerebral blood flow and cerebral blood volume after cerebral ischaemia

CBF obtained by the hydrogen clearance technique and cerebral blood volume (CBV) calculated from the [14C]dextran space were measured in three groups of rats subjected to temporary four-vessel occlusion to produce 15 min of ischaemia, followed by 60 min of reperfusion. In the control animals, mean CBF was 93 +/- 6 ml 100 g-1 min-1, which fell to 5.5 +/- 0.5 ml 100 g-1 min-1 during ischaemia. There was a marked early postischaemic hyperaemia (262 +/- 18 ml 100 g-1 min-1), but 1 h after the onset of ischaemia, there was a significant hypoperfusion (51 +/- 3 ml 100 g-1 min-1). Mean cortical dextran space was 1.58 +/- 0.09 ml 100 g-1 prior to ischaemia. Early in reperfusion there was a significant increase in CBV (1.85 +/- 0.24 ml 100 g-1) with a decrease during the period of hypoperfusion (1.33 +/- 0.03 ml 100 g-1). Therefore, following a period of temporary ischaemia, there are commensurate changes in CBF and CBV, and alterations in the permeability-surface area product at this time may be due to variations in surface area and not necessarily permeability.     

Oscillations in cerebral blood flow detected with a transcranial Doppler index.

Although transcranial Doppler ultrasound (TCD) has been used to detect oscillations in CBF, interpretation is severely limited, since only blood velocity and not flow is measured. Oscillations in vessel diameter could, therefore, mask or alter the detection of those in flow by TCD velocities. In this report, the authors use a TCD-derived index of flow to detect and quantify oscillations of CBF in humans at rest. A flow index (FI) was calculated from TCD spectra by averaging the intensity weighted mean in a beat-by-beat manner over 10 seconds. Both FI and TCD velocity were measured in 16 studies of eight normal subjects at rest every 10 seconds for 20 minutes. End tidal CO2 and blood pressure were obtained simultaneously in six of these studies. The TCD probe position was meticulously held constant. An index of vessel area was calculated by dividing FI by velocity. Spectral estimations were obtained using the Welch method. Spectral peaks were defined as peaks greater than 2 dB above background. The frequencies and magnitudes of spectral peaks of FI, velocity, blood pressure, and CO2 were compared with t tests. The Kolmogorov-Smirnov test was used to further confirm that the data were not white noise. In most cases, three spectral peaks (a, b, c) could be identified, corresponding to periods of 208+/-93, 59+/-31, and 28+/-4 (SD) seconds for FI, and 196+/-83, 57+/-20, and 28+/-6, (SD) seconds for velocity. The magnitudes of the spectral peaks for FI were significantly greater (P<0.02) than those for velocity. These magnitudes corresponded to variations of at least 15.6%, 9.8%, and 6.8% for FI, and 4.8%, 4.2%, and 2.8% for velocity. The frequencies of the spectral peaks of CO2 were similar to those of FI with periods of 213+/-100, 60+/-46, and 28+/-3.6 (SD) seconds. However, the CO2 spectral peak magnitudes were small, with an estimated maximal effect on CBF of (+/-) 2.5+/-0.98, 1.5+/-0.54, and 1.1+/-0.31 (SD) percent. The frequencies of the blood pressure spectral peaks also were similar, with periods of 173+/-81, 44+/-8, and 26+/-2.5 (SD) seconds. Their magnitudes were small, corresponding to variations in blood pressure of (+/-) 2.1+/-0.55, 0.97+/-0.25, and 0.72+/-0.19 (SD) percent. Furthermore, coherence analysis showed no correlation between CO2 and FI, and only weak correlations at isolated frequencies between CO2 and velocity, blood pressure and velocity, or blood pressure and FI. The Kolmogorov-Smirnov test distinguished our data from white noise in most cases. Oscillations in vessel flow occur with significant magnitude at three distinct frequencies in normal subjects at rest and can be detected with a TCD-derived index. The presence of oscillations in blood velocity at similar frequencies but at lower magnitudes suggests that the vessel diameters oscillate in synchrony with flow. Observed variations in CO2 and blood pressure do not explain the flow oscillations. Ordinary TCD velocities severely underestimate these oscillations and so are not appropriate when small changes in flow are to be measured.     

Role of nitric oxide in the cerebral circulation during hypotension after hemorrhage, ganglionic blockade and diazoxide in awake goats

The role of nitric oxide in cerebrovascular response to hypotension was analyzed by evaluating the changes in cerebrovascular resistance after inhibition of nitric oxide synthesis with Nw-nitro-L-arginine methyl ester (L-NAME) during three types of hypotension in conscious goats. Blood flow to one brain hemisphere was electromagnetically measured, hypotension was induced by controlled bleeding, and by i.v. administration of hexametonium (ganglionic blocker) or of diazoxide (vasodilator drug), and L-NAME was injected by i.v. route (35 mg kg-1). Under control conditions (13 goats), L-NAME increased arterial pressure from 98 +/- 3 to 123 +/- 4 mmHg and decreased cerebral blood flow from 65 +/- 3 to 40 +/- 3 ml min-1 (all P < 0.001); cerebrovascular resistance increased from 1.52 +/- 0.04 to 3.09 +/- 0.013 mmHg ml-1 min-1 (P < 0.01) (delta = 1.59 +/- 0.12 mmHg ml-1 min-1). After bleeding (five goats), mean arterial pressure decreased to 60 +/- 4 mmHg and cerebral blood flow decreased to 37 +/- 4 ml min-1 (all P < 0.01); cerebrovascular resistance did not change (1.56 +/- 0.14 vs. 1.54 +/- 0.12 mmHg ml-1 min-1, P > 0.05). During this hypotension, L-NAME increased arterial pressure to reach the normotensive values an did not affect the hypotensive values for cerebral blood flow; cerebrovascular resistance increased from the hypotensive values to 2.91 +/- 0.19 mmHg ml-1 min-1 (P < 0.01) (delta = 1.37 +/- 0.16 mmHg ml-1 min-1), and this increment is comparable to that under control conditions (P > 0.05). Ganglionic blockade (six goats) decreased arterial pressure to 67 +/- 2 mmHg) and did not affect significantly cerebral blood flow; cerebrovascular resistance decreased from 1.71 +/- 0.11 to 1.05 +/- 0.09 mmHg ml-1 min-1 (P < 0.01). During this hypotension, L-NAME increased arterial pressure to 103 +/- 6 mmHg (P < 0.001), and did not affect cerebral blood flow; cerebrovascular resistance increased from the hypotensive values to 1.68 +/- 0.18 mmHg ml-1 min-1 (P < 0.01) (delta = 0.63 +/- 0.10 mmHg ml-1 min-1), and this increment was lower than under control conditions (P < 0.01). Diazoxide (six goats) decreased arterial pressure to 69 +/- 5 mmHg (P < 0.01) without changing cerebral blood flow; cerebrovascular resistance decreased from 1.89 +/- 0.11 to 1.16 +/- 0.14 mmHg ml-1 min-1 (P < 0.01). During this hypotension, L-NAME increased arterial pressure to 87 +/- 6 mmHg (P < 0.05) and did not affect the hypotensive values for cerebral blood flow (P > 0.05); cerebrovascular resistance increased from the hypotensive values to 1.53 +/- 0.13 mmHg ml-1 min-1 (P < 0.05) (delta = 0.36 +/- 0.06 mmHg-1 ml-1 min-1), and this increment was lower than under control conditions (P < 0.01). Therefore, the role of nitric oxide in cerebrovascular response to hypotension may differ in each type of hypotension, as this role during hemorrhagic hypotension may not change and during hypotension by ganglionic blockade or diazoxide may decrease. These differences may be related to changes in nitric oxide release as stimuli on the endothelium (shear stress and sympathetic activity) may vary in each type of hypotension.     

Cerebellar blood flow and metabolism in cerebral hemisphere infarction

Positron emission tomography was used to study the effect of supratentorial infarction on cerebellar metabolic rate for oxygen and cerebellar blood flow. In a control group of patients, the mean cerebellar metabolic rate for oxygen was 2.97 +/- 0.11 (standard error of the mean [SEM] ) ml-1 . min-1 . hg-1 and mean cerebellar blood flow was 41.1 +/- 1.5 ml . min-1 . hg-1. No significant right-left asymmetry in either cerebellar metabolic rate for oxygen or cerebellar blood flow was noted. Patients with frontal lobe infarction showed 16.8 +/- 1.8% (cerebellar metabolic rate for oxygen) and 19.6 +/- 2.1% (cerebellar blood flow) differences between cerebellar hemispheres, with the hemisphere contralateral to the cerebral infarction having the lower values. These differences were highly significant (p less than 0.001). In addition, cerebellar blood flow and cerebellar metabolic rate for oxygen were significantly decreased in the ipsilateral cerebellar hemisphere (metabolism: 2.13 +/- 0.19 ml . min-1 . hg-1; p less than 0.002; blood flow: 35.2 +/- 2.4 ml . min-1 . hg-1; p less than 0.05). Patients with parietooccipital infarction also showed a significant bilateral decrease in cerebellar metabolic rate for oxygen (2.43 +/- 0.11 ml . min-1 . hg-1) and cerebellar blood flow (34.6 +/- 2.5 ml . min-1 . hg-1) relative to control subjects, but no significant cerebellar asymmetry. Our findings demonstrate a general depression of cerebellar blood flow and metabolism from cerebral hemisphere infarction unrelated to the site of infarction as well as a specific depression occurring contralateral to infarction involving the frontal lobe. These are among the first quantitative data concerning regional cerebellar metabolic rates for oxygen and cerebellar blood flow in humans.