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.     

EFFECTS OF NORADRENALINE ON THE CEREBRAL BLOOD FLOW IN THE DOG

The cerebrovascular response to intravenous noradrenaline infusion was studied in anaesthetized dogs during different and carefully controlled blood gas and arterial blood pressure conditions, using the radioactive gas elimination technique with external γ-registration. A flow reduction was found both at normocapnia and hypercapnia. Furthermore, in arterial hypoxia, which had induced vasodilatation a corresponding vasoconstriction was found. The response could be blocked by the α-adrenergic blocking agent phentolamine. Autoregulation of cerebral blood flow was found to function well during the influence of noradrenaline as well as after adrenergic α-receptor blocking by phentolamine.     

Effect of aging on cerebral vascular response to Paco2 changes in humans as measured by positron emission tomography.

Vascular responses to changes in Paco2 are used widely to estimate cerebral perfusion reserve, and they can also be used to assess the degree of arteriosclerosis. In the present study, the effect of aging on cerebral vascular responses to both hypercapnia and hypocapnia was investigated. Cerebral blood flow was measured with positron emission tomography at rest, during hypercapnia, and during hypocapnia in 11 young men and 12 older men. The vascular response to change in Paco2 was calculated as the percent change in cerebral blood flow per absolute change in Paco2 in response to hypercapnia and hypocapnia. The total vascular response to change in Paco2 from hypocapnia to hypercapnia was also calculated. To evaluate age-related changes in regional cerebral vascular responses on a pixel-by-pixel basis, an anatomic standardization technique was also used. Although no significant differences between young and old subjects was observed for vascular responses to both hypercapnia and hypocapnia, a significant decrease in total vascular response was observed with aging, indicating progression of sclerotic changes in the cerebral perforating and medullary arteries with normal aging. According to anatomic standardization analysis, relative capacities for vasodilatation in the cerebellum and insular cortex, and relative capacity for vasoconstriction in the frontal cortex were greater in the younger subjects. Such aging effects should be considered when estimating cerebral perfusion reserve.     

Multimodality monitoring during passive tilt and Valsalva maneuver under hypercapnia.

In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be guaranteed. Therefore, an assessment of cerebral autoregulation should consider not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva maneuver (VM) are established tests for cardiovascular autoregulatory function by provoking BP changes. To develop a comprehensive test for vasomotor reactivity with a potential increase of sensitivity and specificity, the authors combined these maneuvers. Blood pressure, corrected to represent arterial pressure at the level of the circle of Willis, middle cerebral artery Doppler frequencies (DF), heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2) and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced only minor, nonsignificant changes in mean BP at the level of the circle of Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13 mm Hg). This corresponded with a nonsignificant decrease of the mean of DF (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced pulsatility of BP by a predominantly diastolic increase of BP without significant changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid changes of BP due to elevated intrathoracic pressure, showed no significant BP differences in changes to baseline between normocapnic and hypercapnic conditions. Under both conditions the decrease in BP in phase II was accompanied by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver and PT as established tests in autonomic control of circulation provoked not only changes in time-mean of BP but also in pulsatility of BP. The significant increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2 partial pressures. Hypercapnia did not significantly influence the autoregulatory indices during VM and PT. Physiologically submaximally dilated cerebral arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined BP and MCA-DF assessment under hypercapnia enables investigating the effect of rapid changes of blood pressure on CO2-induced predilated cerebral arterioles. Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid, distinct changes in BP, seems especially to be adequate provocation for CBF autoregulation. This combined vasomotor reactivity might provide a more sensitive diagnostic tool to detect impaired cerebral autoregulation very early.     

The effect of caffeine on dilated cerebral circulation and on diagnostic CO2 reactivity testing.

Reduction of cerebral blood flow by caffeine has been shown in multiple studies. However, the effect of this substance on pathologically dilated cerebral vessels is not clearly defined. The aim of this study was to investigate the effect of caffeine on an already dilated cerebral circulation and specify if these vessels are still able to constrict as a consequence of caffeine stimulation. A second aim of this study was to compare results of cerebral vasomotor CO(2) reactivity testing with and without caffeine ingestion. Seventeen healthy adult volunteers had vasomotor reactivity tested before and thirty minutes after ingestion of 300 mg of caffeine. Each vasomotor reactivity test consisted of velocity measurements from both middle cerebral arteries using transcranial Doppler ultrasound during normocapnia, hypercapnia, and hypocapnia. Hemodynamic data and end-tidal CO(2) (etCO(2)) concentration were also recorded. The vasomotor reactivity (VMR) and CO(2) reactivity were calculated from a measured data pool. At a level of etCO(2)=40 mmHg the resting velocity in the middle cerebral artery (V(MCA)) dropped from 70.7+/-22.8 cm/sec to 60.7 +/- 15.4 cm/sec 30 minutes after caffeine stimulation (14.1% decrease, p<0.001). During hypercapnia of etCO(2)=50 mmHg there was also a significant decline of V(MCA) from 103.1+/-25.4 to 91.4+/-21.8 cm/sec (11.3%, p<0.001). There was not a statistically significant reduction of V(MCA) during hypocapnia. Calculated VMR and CO(2) reactivity before and after caffeine intake were not statistically significant. The presented data demonstrate a significant decrease in cerebral blood flow velocities after caffeine ingestion both in a normal cerebrovascular bed and under conditions of peripheral cerebrovascular vasodilatation. These findings support the important role of caffeine in regulation of CBF under different pathological conditions. Despite significant reactive vasodilatation in the brain microcirculation, caffeine is still able to act as a competitive antagonist of CO(2) on cerebral microvessels. The fact that caffeine may decrease CBF despite significant pathological vasodilatation offers the possibility of therapeutic manipulation in patients with traumatic vasoparalysis. For routine clinical testing of CO(2) reactivity it is not necessary to insist on pre-test dietary restrictions.     

Stable xenon versus radiolabeled microsphere cerebral blood flow measurements in baboons

Regional cerebral blood flow was simultaneously determined using the stable xenon computed tomographic and the radioactive microsphere techniques over a wide range of blood flow rates (less than 10-greater than 300 ml/100 g/min) in 12 baboons under conditions of normocapnia, hypocapnia, and hypercapnia. A total of 31 pairs of determinations were made. After anesthetic and surgical preparation of the baboons, cerebral blood flow was repeatedly determined using the stable xenon technique during saturation with 50% xenon in oxygen. Concurrently, cerebral blood flow was determined before and during xenon administration using 15-microns microspheres. In Group 1 (n = 7), xenon and microsphere determinations were made repeatedly during normocapnia. In Group 2 (n = 5), cerebral blood flow was determined using both techniques in each baboon during hypocapnia (PaCO2 = 20 mm Hg), normocapnia (PaCO2 = 40 mm Hg), and hypercapnia (PaCO2 = 60 mm Hg). Xenon and microsphere values in Group 1 were significantly correlated (r = 0.69, p less than 0.01). In Group 2, values from both techniques also correlated closely across all levels of PaCO2 (r = 0.92, p less than 0.001). No significant differences existed between the slopes or y intercepts of the regression lines for either group and the line of identity. Our data indicate that the stable xenon technique yields cerebral blood flow values that correlate well with values determined using radioactive microspheres across a wide range of cerebral blood flow rates.     

Effect of basal conditions on the magnitude and dynamics of the blood oxygenation level-dependent fMRI response.

The effect of the basal cerebral blood flow (CBF) on both the magnitude and dynamics of the functional hemodynamic response in humans has not been fully investigated. Thus, the hemodynamic response to visual stimulation was measured using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in human subjects in a 7-T magnetic field under different basal conditions: hypocapnia, normocapnia, and hypercapnia. Hypercapnia was induced by inhalation of a 5% carbon dioxide gas mixture and hypocapnia was produced by hyperventilation. As the fMRI baseline signal increased linearly with expired CO2 from hypocapnic to hypercapnic levels, the magnitude of the BOLD response to visual stimulation decreased linearly. Measures of the dynamics of the visually evoked BOLD response (onset time, full-width-at-half-maximum, and time-to-peak) increased linearly with the basal fMRI signal and the end-tidal CO2 level. The basal CBF level, modulated by the arterial partial pressure of CO2, significantly affects both the magnitude and dynamics of the BOLD response induced by neural activity. These results suggest that caution should be exercised when comparing stimulus-induced fMRI responses under different physiologic or pharmacologic states.     

Carbon dioxide induced changes in cerebral blood flow and flow velocity: role of cerebrovascular resistance and effective cerebral perfusion pressure

In addition to cerebrovascular resistance (CVR) zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe) and the resistance area product (RAP) are supplemental determinants of cerebral blood flow (CBF). Until now, the interrelationship of PaCO₂-induced changes in CBF, CVR, CPPe, ZFP, and RAP is not fully understood. In a controlled crossover trial, we investigated 10 anesthetized patients aiming at PaCO₂ levels of 30, 37, 43, and 50 mm Hg. Cerebral blood flow was measured with a modified Kety-Schmidt-technique. Zero flow pressure and RAP was estimated by linear regression analysis of pressure–flow velocity relationships of the middle cerebral artery. Effective cerebral perfusion pressure was calculated as the difference between mean arterial pressure and ZFP, CVR as the ratio CPPe/CBF. Statistical analysis was performed by one-way RM-ANOVA. When comparing hypocapnia with hypercapnia, CBF showed a significant exponential reduction by 55% and mean V_MCA by 41%. Effective cerebral perfusion pressure linearly decreased by 17% while ZFP increased from 14 to 29 mm Hg. Cerebrovascular resistance increased by 96% and RAP by 39% despite these concordant changes in mean CVR and Doppler-derived RAP correlation between these variables was weak (r=0.43). In conclusion, under general anesthesia hypocapnia-induced reduction in CBF is caused by both an increase in CVR and a decrease in CPPe, as a consequence of an increase in ZFP.     

Vasomotor reactivity in dementia of alzheimer type

The objective of this study was to examine the cerebral blood flow and the vasomotor function of CO₂-responsive intracerebral vessels in Alzheimer's disease. Patients met DSM-III-R criteria for dementia of Alzheimer type and had neither symptoms nor signs of cardiovascular or cerebrovascular disease. Blood flow velocities in both middle cerebral arteries (MCA) were recorded using transcranial Doppler sonography during hypercapnia, normocapnia and hypocapnia. Several psychometric tests were performed. Patients' age, disease duration and severity of dementia did not correlate with vasomotor reactivity. Exploratory analysis revealed that mean flow velocities under hypercapnia correlated with severity of dementia and with patient's age. This suggests that the disease process does not influence the autoregulative function of small resistance vessels as assessed by CO₂ challenge. However, the excess reduction of the highest flow velocities measured during maximal CO₂ stimulation indicates that the number of small capillaries are diminished, or alternatively that the diameters of these capillaries are reduced in Alzheimer's disease.     

Fourier analysis of the cerebrovascular system

We performed Fourier analysis of the middle cerebral artery blood flow velocity waveform envelope in 14 normal subjects (group A) and 15 patients, of whom five had arteriovenous malformations (group B), five had cerebral vasospasm (group C), and five had arterial hypertension (group D). Measurements were obtained under conditions of normocapnia, hypercapnia, and hypocapnia. The Fourier coefficients measured in the first five harmonics of the Doppler waveforms of group A were used as the reference baseline and were compared with the coefficients found in the other three groups. Group B showed significantly lower Fourier coefficients, while groups C and D showed higher coefficients (p less than 0.05). The elevation of the Fourier coefficients occurred in an alternating pattern in group C and a decremental pattern in group D. This distinction was attributed to possible differences in the underlying pathophysiological processes. The degree of vascular distensibility of the cerebral arterioles, inferred from the shape of the Fourier analysis curves, was compared in all four groups. Vascular distensibility was characterized as abnormal in arteriovenous malformations, vasospasm, and arterial hypertension. Fourier coefficients may be better indicators of cerebrovascular abnormalities than mean blood flow velocity in hypertension and pulsatility index in arteriovenous malformations, vasospasm, and hypertension.     

Time-dependent effects of prolonged hypercapnia on cerebrovascular parameters in dogs: acid-base chemistry

Prolonged normoxic hypercapnia initially caused an increase in canine cerebral blood flow, as measured by the radioactive microsphere technique, accompanied by a decrease in cerebrovascular resistance. These effects persisted for 3 hours. An adaptive decrease in cerebral blood flow and increase in cerebrovascular resistance were seen when hypercapnia was maintained for an additional 3 hours. Regional variations occurred; those areas with the greatest initial hypercapnic blood flow (cortex, caudate nucleus) showed a greater rate of decay of flow over time. Cerebrospinal fluid pH, initially acidotic during hypercapnia, increased over the subsequent 5 hours from 6.99 +/- 0.02 to 7.13 +/- 0.02. This was accompanied by an increase in the cerebrospinal fluid bicarbonate ion concentration from a normocapnic baseline of 19.6 +/- 0.6 to 26.2 +/- 4 mEq/l. Total and regional cerebral blood flow were linearly related to cerebrospinal fluid pH (R2 = 0.97). Extrapolation of a full adaptive return of flow to baseline indicated a shift in the cerebrovascular sensitivity to extracellular hydrogen ion concentration during prolonged hypercapnia.     

Interaction between central-peripheral chemoreflexes and cerebro-cardiovascular control

Abstract We investigated the interaction between hypoxia and hypercapnia on ventilation and on cerebro-cardio-vascular control. A group of 12 healthy subjects performed rebreathing tests to determine the ventilatory response to hypoxia, at different levels of carbon dioxide (CO₂), and to normoxic hypercapnia.Oxygen saturation (SaO₂), end-tidal CO₂ (et-CO₂), minute ventilation, blood pressure, R-R interval and mid-cerebral artery flow velocity (MCFV) were continuously recorded. The hypoxic ventilatory response significantly increased under hypercapnia and decreased under hypocapnia (slopes L/min/% Sa O₂: –0.33±0.05, –0.74±0.02 and –1.59±0.3, p<0.0001, in hypocapnia, normocapnia and hypercapnia, respectively). At similar degrees of ventilation, MCFV increased more markedly during normocapnic hypoxia than normoxic hypercapnia; the slopes linking MCFV to hypoxia remained unchanged at increasing levels of et-CO₂, whereas the regression lines were shifted upward. The R-R interval decreased more markedly during normocapnic hypoxia than normoxic hypercapnia and the arterial baroreflex sensitivity was decreased only by hypoxia. Cardiovascular responses to hypoxia were not affected by different levels of et-CO₂. We conclude that concomitant hypoxia and hypercapnia, while increasing ventilation synergistically, exert an additive effect on cerebral blood flow. Increased sympathetic activity (and reduced baroreflex sensitivity) is one of the mechanisms by which hypoxia stimulates cardiac sympathetic activity.     

Changes of cerebral blood flow in the basilar artery system in patients with neurogenic syncope

Syncope is a short loss of consciousness caused by a transient decrease of global cerebral blood flow. Neurally mediated syncope is associated with vasodilatory response and bradycardia. The Doppler ultrasonography was used to evaluate changes of the basilar artery blood flow mean velocity and pulsatility index during orthostatic challenge and CO2 reactivity testing in patients with neurally mediated syncope and a negative result of the Tilt Test. Eighteen patients aged 20-40 years with a history of cerebral syncope and 10 healthy volunteers were qualified. RESULTS: There were no significant differences between syncope patients and controls in the basilar artery blood flow parameters in various body positions during normocapnia, hypocapnia and hypercapnia. Irrespective of body position, the reactivity index in patients with neurally mediated syncope was lower than that in controls, but not significantly. CONCLUSIONS: No significant pathology was found in cerebrovasoreactivity responses in the area supplied by the basilar artery, which suggests that cerebral autoregulation disorders cannot be the primary cause of neurally mediated syncope.     

Effects of increased arterial pressure on blood flow in the damaged brain.

The effect of induced arterial hypertension on cerebral blood flow and intracranial pressure was measured before and after the production of a standard cryogenic brain lesion in 10 anaesthetized, ventilated baboons. Before injury the animals were divided into a group with intact autoregulation, having more than 20% increase in cerebrovascular resistance during arterial hypertension, and a group with impaired autoregulation, in which the change in cerebrovascular resistance was much less. The cryogenic injury produced a rapid rise in intracranial pressure and a reduction of cerebral blood flow in the affected hemisphere. Despite this, there was an increase in cerebrovascular resistance during arterial hypertension in all animals after brain injury, accompanied by a further significant rise in intracranial pressure. It is suggested that this response is unlikely to represent normal physiological autoregulation and caution should be exercised in interpreting it as such in the course of studies of cerebral blood flow in patients with acute brain damage.     

Abnormal cerebrovascular response to altered PaCO2 in baboons with obstructive jaundice.

The cerebrovascular response to hypercapnia and hyperventilation was studied in normal and jaundiced baboons by the intracarotid 133Xe injection technique. The baboons with bile duct ligation were found to have decreased CBF at all levels of PaCO2. This difference between normal and jaundiced baboons was 13% at normocapnia rising to 33% with hypercapnia and 37% with hypocapnia. The CBF values all were increased toward normal by use of an alpha-adrenoreceptor blockade (phentolamine). It is suggested that the obstructive jaundice potentiated an inherent vasoconstrictor alpha-adrenergic mechanism to oppose the effects of CO2. Also, alteration of the PaCO2 may have produced its effects on the cerebral vessels by altering this adrenergic mechanism.     

Regional cerebral blood flow during hypercapnia in the anesthetized rabbit

These experiments were designed to test the hypothesis that increases in blood flow to the lower brainstem would be greater than forebrain regions during arterial hypercapnia. Total and regional cerebral blood flow (CBF) was measured via the tracer microsphere technique in seven anesthetized New Zealand white rabbits during normocapnia (arterial PCO2 congruent to 40 torr) and hypercapnia (arterial PCO2 congruent to 80 torr). During normocapnia average CBF was 0.77 ml/min/g, and regional measurements of blood flow indicated significantly greater flow to the cerebrum (0.86 ml/min/g) than either the medulla (0.52 ml/min/g) or the pons (0.49 ml/min/g). When arterial PCO2 was increased average CBF increased 113%, and a significant linear regression was calculated for arterial PCO2 vs CBF [CBF (ml/min/g) = 0.028 PCO2 (torr) - 0.502]. The distribution of blood flow within the brain was similar to normocapnia except that blood flow to the cerebellum was now greater than any other brain region (1.97 ml/min/g for the cerebellum compared to 1.66 ml/min/g for the cerebrum). Absolute increases in blood flow to the lower brainstem were equal to or less than other areas of the brain. We conclude that ponto-medullary blood flow does not increase disproportionate to other areas of the brain during hypercapnia, but some redistribution of CBF does occur in that cerebellar blood flow increased significantly more than the cerebrum, medulla, or pons.     

Cerebral vasoreactivity in hypocapnia and hypercapnia in patients with diabetes mellitus type 2 with or without arterial hypertension

Background and purposeDiabetes mellitus (DM) is an independent risk factor for cardiovascular diseases. The origin of diabetic microangiopathy is multifactorial; it affects all layers of the artery wall, causing endothelial and vasoreactivity impairment. The incidence of cerebral vasoreactivity failure in diabetic patients without stroke history is not precisely determined yet. The aim of the study was to assess the cerebrovascular reactivity in hypocapnia and hypercapnia in patients with type 2 DM with or without arterial hypertension without artery stenosis and stroke history, with the use of transcranial Doppler examination.Material and methodsThe mean blood flow velocity, pulsatility index and parameters of cerebrovascular reactivity were measured in 53 patients with type 2 DM (aged 42–72 years, mean 59.5 ± 7.9) and in 27 healthy volunteers (aged 36–74 years, mean 57.0 ± 10.4). Diabetics were further divided into two subgroups according to the presence or absence of arterial hypertension.ResultsThe index of cerebrovascular reactivity in hypocapnia and hypercapnia was significantly worse and time needed to normalization of blood flow velocity was significantly longer in patients with DM in comparison with healthy volunteers.ConclusionsMost DM type 2 patients without stroke history had decreased values of cerebral vasoreactivity parameters, which suggests the presence of microangiopathy.     

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.     

Changes in the arterial fraction of human cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography.

Hypercapnia induces cerebral vasodilation and increases cerebral blood volume (CBV), and hypocapnia induces cerebral vasoconstriction and decreases CBV. Cerebral blood volume measured by positron emission tomography (PET) is the sum of three components, that is, arterial, capillary, and venous blood volumes. Changes in arterial blood volume (V(a)) and CBV during hypercapnia and hypocapnia were investigated in humans using PET with H(2)(15)O and (11)CO. Arterial blood volume was determined from H(2)(15)O PET data by means of a two-compartment model that takes V(a) into account. Baseline CBV and values during hypercapnia and hypocapnia in the cerebral cortex were 0.034+/-0.003, 0.038+/-0.003, and 0.031+/-0.003 mL/mL (mean+/-s.d.), respectively. Baseline V(a) and values during hypercapnia and hypocapnia were 0.015+/-0.003, 0.025+/-0.011, and 0.007+/-0.003 mL/mL, respectively. Cerebral blood volume changed significantly owing to changes in PaCO(2), and V(a) changed significantly in the direction of CBV changes. However, no significant change was observed in venous plus capillary blood volume (=CBV-V(a)). This indicates that changes in CBV during hypercapnia and hypocapnia are caused by changes in arterial blood volume without changes in venous and capillary blood volume.     

Cholinergic cerebral vasodilatation in the rabbit: absence of concomitant metabolic activation

Cerebral blood flow (CBF) was estimated from measurements of internal carotid blood flow and sagittal sinus blood flow in mechanically ventilated rabbits under 70% N2O-30% O2. Intravenously administered physostigmine, a cholinesterase inhibitor, increased CBF under normocapnia and enhanced the cerebral vasodilatation of hypercapnia, but did not alter the cerebral metabolic rate of oxygen (CMRO2). The cerebrovascular effects of physostigmine were antagonized by atropine but not by dihydro-beta-erythroidine, a nicotinic blocker. Neostigmine, a quaternary cholinesterase inhibitor that does not cross the blood-brain barrier, showed no cerebrovascular effects. It is concluded that the cholinergic cerebral vasodilatation does not depend on cerebral metabolic activation, and that the cholinergic receptors involved are muscarinic and located beyond the blood-brain barrier.