MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis

BACKGROUND AND PURPOSE: The relationship between middle cerebral artery (MCA) flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown vessel diameter response to physiological stimuli. The purpose of this study was to directly examine the effect of a simulated orthostatic stress (lower body negative pressure [LBNP]) as well as increased or decreased end-tidal carbon dioxide partial pressure (P(ET)CO(2)) on MCA diameter and CFV. METHODS: Twelve subjects participated in a CO(2) manipulation protocol and/or an LBNP protocol. In the CO(2) manipulation protocol, subjects breathed room air (normocapnia) or 6% inspired CO(2) (hypercapnia), or they hyperventilated to approximately 25 mm Hg P(ET)CO(2) (hypocapnia). In the LBNP protocol, subjects experienced 10 minutes each of -20 and -40 mm Hg lower body suction. CFV and diameter of the MCA were measured by transcranial Doppler and MRI, respectively, during the experimental protocols. RESULTS: Compared with normocapnia, hypercapnia produced increases in both P(ET)CO(2) (from 36+/-3 to 40+/-4 mm Hg, P<0.05) and CFV (from 63+/-4 to 80+/-6 cm/s, P<0.001) but did not change MCA diameters (from 2.9+/-0.3 to 2.8+/-0.3 mm). Hypocapnia produced decreases in both P(ET)CO(2) (24+/-2 mm Hg, P<0.005) and CFV (43+/-7 cm/s, P<0.001) compared with normocapnia, with no change in MCA diameters (from 2.9+/-0.3 to 2.9+/-0.4 mm). During -40 mm Hg LBNP, P(ET)CO(2) was not changed, but CFV (55+/-4 cm/s) was reduced from baseline (58+/-4 cm/s, P<0.05), with no change in MCA diameter. CONCLUSIONS: Under the conditions of this study, changes in MCA diameter were not detected. Therefore, we conclude that relative changes in CFV were representative of changes in CBF during the physiological stimuli of moderate LBNP or changes in P(ET)CO(2).     

Dynamic cerebral autoregulation testing as a diagnostic tool in patients with carotid artery stenosis

Evaluation of dynamic cerebral autoregulation might yield a physiologically more adequate measure of cerebral hemodynamic impairment in carotid artery stenosis than CO2-reactivity. This study re-evaluates and compares the Valsalva maneuver (VM) and phase shift during deep breathing. Nineteen patients with severe carotid artery stenosis and 17 age-matched controls were examined using transcranial Doppler sonography and non-invasive blood pressure recordings (Finapres). Phase shift was determined by cross-spectral analysis, responses to VM were graded by the formerly-introduced autoregulation slope index (ASI) and the new Valsalva time index (VTI). Phase shift and autoregulatory indices were significantly reduced on the affected side (p < 0.001). Correlations with CO2-reactivity were significant when pooling values of controls and patients (r from 0.54 to 0.78; p < 0.001). Correlations except for the VTI (r = -0.65; p = 0.002) were not significant considering only the affected side in patients. Correlations of pooled values between phase shift and VM-derived indices were significant (VTI r = -0.62; p < 0.001; ASI r = 0.49; p < 0.001), within patients only when comparing side-to-side differences (VTI r = -0.58; p = 0.009; ASI r = 0.52; p = 0.023). In conclusion, detection of impaired cerebral autoregulation is possible both by deep breathing and VM. The new VTI seems to be more suitable than the conventional ASI. Inter-method agreement concerning the extent of impairment is only acceptable for intra-individual side-to-side differences. Since absolute values of one autoregulation testing method or CO2-reactivity alone might fail, various tests should be combined for comprehensive assessment of cerebral hemodynamic impairment.     

Cerebral syncope: insights from Valsalva maneuver

BACKGROUND AND PURPOSE: Cerebral syncope refers to a loss of consciousness associated with cerebral vasoconstriction in the absence of systemic hypotension. The diagnosis of cerebral syncope could be established by the head-up tilt test (HUT) and transcranial Doppler ultrasonography. Valsalva maneuver (VM) permitted assessment of cerebral autoregulatory function by provoking blood pressure (BP) changes. To develop a path-physiological approach for vasomotor reactivity of cerebral syncope, the authors combined these maneuvers (HUT/transcranial Doppler/VM). METHODS: Using transcranial Doppler ultrasonography, we simultaneously recorded systemic arterial BP in the radial artery and flow velocities in both middle cerebral arteries (MCAFV) in 10 cerebral syncope patients (4 males and 6 females, 35.24 +/- 4.5 years old) during the Valsalva maneuver. RESULTS: The characteristic changes in BP (phases I-IV) were seen in all subjects, accompanying distinct changes in cerebral blood flow velocity. The BP/heart rate responding to VM was within normal limit in all subjects. There was no orthostatic hypotension. Instead, BP increased during the tilting test in 2 subjects (20.00%). The MCAFV dropped 25.4 +/- 2.3% from baseline. Abnormal flattening of MCAFV during late phase II (IIb), the paradoxical drop of flow velocity despite restoration of BP, was noted in 9 subjects (90.00%). CONCLUSION: During VM there are complex changes in relevant cardiovascular and cerebrovascular variables within a short time span. The paradoxical drop of MCAFV during phase IIb was the result of complex parameters. Among them, a failure in cerebrovascular resistance reduction and even paradoxical vasoconstriction might further compromise cerebral perfusion pressure and lead to syncope.     

Challenging cerebral autoregulation in patients with preganglionic autonomic failure

Intact cerebral autoregulation is essential to prevent cerebral hypoperfusion during pronounced changes in arterial blood pressure (ABP) in patients with autonomic failure (AF). It is still a matter of debate whether and to what extent cerebral autoregulation is disturbed in these patients. This study evaluates the interaction between cerebral blood flow velocity (CBFV) and ABP during Valsalva maneuver (VM) and tilt-table testing in nine patients with multiple system atrophy including AF and in 14 age-matched controls. CBFV and ABP were recorded noninvasively using transcranial Doppler sonography and the Finapres device. Responses to VM were graded by the autoregulation slope index (ASI). Cerebrovascular resistance changes were estimated by the conventional ratio ABP/CBFV and by the dynamic pressure-velocity relationship. To challenge cerebral autoregulation further, tests were repeated under hypercapnic predilation of cerebral arterioles. During VM, CBFV reincreased in patients despite a pronounced ABP drop and showed an overshoot after the strain, thus, being similar to controls. The ASI was higher in patients than in controls ( p < 0.05). During 70 degrees head-up tilt, ABP dropped markedly, but the decrease in CBFV was small and did not differ significantly from controls. In patients, both tests were associated with a substantial decrease of the dynamic but not of the conventional pressure-velocity relationship. Under hypercapnia, the CBFV response in patients remained unchanged. We conclude that 1). cerebral arterioles have the capacity for adequate vasodilation during ABP drops in patients with AF and that this ability is still present under hypercapnic predilation. 2). The mechanism of cerebral autoregulation in itself does not seem to be affected by the AF but is rather well exercised. 3) The VM presents, in addition to tilt-table testing, a simple test for clinical evaluation of cerebral autoregulation in patients with AF.     

Cerebral blood flow regulation: vascular resistance adjustments in the circle of Willis.

Continuous measurements of systemic blood pressure (BP), cerebral perfusion pressure and CBF were accomplished in the cat during transient hypertension, hypercapnia and bilateral carotid artery occlusion. From these measurements resistance values in the circle of Willis and in the cerebral arteries distal to the circle were calculated. The results indicate that the arteries of the circle of Willis and the arteries distal to the circle of Willis dilate and contract independently.     

瓦氏动作在脑血流自动调节功能中的应用

CA是指脑血流在动脉血压和脑灌注压发生改变时保持相对稳定的一个复杂的多因素过 程。脑血流自动调节与多种神经系统疾病如脑血管病、帕金森病、头痛、自主神经功能障碍等疾病的 发生、发展及临床预后相关。对脑血流自动调节功能有很多种评估测量方法，监测瓦氏动作所诱导 的血压变化更具有操作性及标准化，适用于各种人群，其安全、简单、准确的特点使其在脑血流自动 调节中运用十分广泛。本文重点对瓦氏动作在脑血流自动调节功能中的应用做一个综述介绍。     

Cerebral autoregulation dynamics in humans

We studied the response of cerebral blood flow to acute step decreases in arterial blood pressure noninvasively and nonpharmacologically in 10 normal volunteers during normocapnia, hypocapnia, and hypercapnia. The step (approximately 20 mm Hg) was induced by rapidly deflating thigh blood pressure cuffs following a 2-minute inflation above systolic blood pressure. Instantaneous arterial blood pressure was measured by a new servo-cuff method, and cerebral blood flow changes were assessed by transcranial Doppler recording of middle cerebral artery blood flow velocity. In hypocapnia, full restoration of blood flow to the pretest level was seen as early as 4.1 seconds after the step decrease in blood pressure, while the response was slower in normocapnia and hypercapnia. The time course of cerebrovascular resistance was calculated from blood pressure and blood flow recordings, and rate of regulation was determined as the normalized change in cerebrovascular resistance per second during 2.5 seconds just after the step decrease in blood pressure. The reference for normalization was the calculated change in cerebrovascular resistance that would have nullified the effects of the step decrease in arterial blood pressure on cerebral blood flow. The rate of regulation was 0.38, 0.20, and 0.11/sec in hypocapnia, normocapnia, and hypercapnia, respectively. There was a highly significant inverse relation between rate of regulation and PaCO2 (p less than 0.001), indicating that the response rate of cerebral autoregulation in awake normal humans is profoundly dependent on vascular tone.     

Cerebrovascular effects of prostaglandin inhibitors in the gerbil

Autoregulation of cerebral blood flow (CBF) to mean arterial blood pressure (MABP) of 40-50 mm Hg has been demonstrated in the spontaneously breathing gerbil anaesthetised with barbiturate (60 mg/kg). CO2 reactivity has also been assessed at 2.8% change CBF/mm Hg change in arterial PCO2. In six animals pretreated with indomethacin (3 mg/kg), autoregulation was preserved although the resting CBF was significantly reduced, but CO2 reactivity was completely abolished. 1-n-Butyl imidazole, a specific thromboxane synthetase inhibitor, was used in six other animals (3 mg/kg), and this abolished CO2 reactivity while preserving autoregulation; the effect of this agent has not been described previously. Both drugs inhibit different pathways of prostaglandin metabolism and may interfere with normal CO2 reactivity in several ways. Two explanations are that prostaglandins constitute the final common pathway in effecting cerebrovascular response to CO2 or, alternatively, that the free radicals and ionic fluxes generated during prostaglandin metabolism are a coincidental source of the hydrogen ion changes required.     

Effect of nitric oxide blockade by NG-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension.

The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of arterial blood pressure and a decrease of normocapnic CBF from 85 +/- 10 to 78 +/- 6, 64 +/- 5, and 52 +/- 5 ml 100 g-1 min-1, respectively. This effect lasted for at least 2 h. Raising PaCO2 from a control level of 40 to 68 mm Hg increased CBF to 230 +/- 27 ml 100 g-1 min-1, corresponding to a percentage CBF response (CO2 reactivity) of 3.7 +/- 0.6%/mm Hg PaCO2 in saline-treated rats. NOLAG attenuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with angiotensin to raise blood pressure to the same level as the highest dose of NOLAG did not affect the CBF response to hypercapnia. L-Arginine significantly prevented the effect of NOLAG on normocapnic CBF as well as blood pressure and also abolished its inhibitory effect on hypercapnic CBF. D-Arginine had no such effect. Decreasing PaCO2 to 20 mm Hg reduced control CBF to 46 +/- 3 ml 100 g-1 min-1 with no further reduction after NOLAG. Furthermore, NOLAG did not change the percentage CBF response to an extracellular acidosis induced by acetazolamide (50 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of 2-chloroadenosine on cerebrovascular reactivity to hypercapnia in newborn pig.

The effect of local administration of vasodilative concentrations of the adenosine receptor agonist 2-chloroadenosine (2-CADO) on the hyperemic responses of the pial and parenchymal microcirculations to graded hypercapnia was determined. The cranial window and brain microdialysis-hydrogen clearance techniques were utilized in two groups of isoflurane-anesthetized newborn pigs to measure changes in pial diameters and local CBF, respectively, in response to graded hypercapnia in the absence and presence of 2-CADO. Progressive size-dependent dilations of pial arterioles [small = 41 +/- 7 microns (mean +/- SD), intermediate = 78 +/- 13 microns, and large = 176 +/- 57 microns in diameter] occurred in response to graded hypercapnia alone (PaCO2 = 58 and 98 mm Hg) and to superfusions of 2-CADO (10(-5) M) during normocapnia; the magnitude of the dilative response to each of these stimuli was inversely proportional to vessel size. When hypercapnia was induced concomitantly with 2-CADO superfusion, the dilative effects of each stimulus were directly additive. Similarly, local microdialysis infusion of 10(-5) M 2-CADO, which doubled CBF during normocapnia, did not affect the hyperemic response of the parenchymal circulation to graded hypercapnia (PaCO2 = 69 and 101 mm Hg). Our findings are consistent with the participation of adenosine in the mediation of cerebral hypercapnic hyperemia. If, however, adenosine is not involved in this dilative response, our results indicate that concomitant vascular and neuromodulatory actions induced by adenosine receptor stimulation do not affect the mechanism responsible for the hypercapnic hyperemic response.     

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.     

Valsalva maneuver suggests increased rigidity of cerebral resistance vessels in familial dysautonomia

In familial dysautonomia (FD), cerebral autoregulation (CA) must adjust cerebral blood flow to extreme and rapid fluctuations in systemic blood pressure. Compromised CA during systemic blood pressure (BP) fluctuations might contribute to central autonomic dysfunction in FD. To evaluate CA during rapid BP changes, we monitored heart rate (HR), radial artery BP and middle cerebral artery blood flow velocity (CBFV), using transcranial Doppler sonography, in eight FD patients and twelve age-matched controls in supine position at baseline and during a Valsalva maneuver (VM, 40 mmHg expiratory pressure for 15 seconds). The best of four VM recordings was analyzed. We calculated two autoregulation parameters. CA_II reflects BP related autoregulatory CBFV increase in late phase II of VM. CA_II = [(CBFV_{II late}-CBFV_{II early})/CBFV_{II early}]/[(BP_{II late}-BP_{II early})/BP_{II early}]. CA_IV reflects BP and HR related autoregulatory CBFV increase in phase IV of VM. CA_IV = (CBFV_IV/CBFV_I)/(BP_IV/BP_I)/(HR_IV/HR_I). Baseline systemic BP, but not CBFV, was higher in the patients than the controls. During VM, both groups had similar CBFV and BP values, but CAIV and especially CA_II were significantly lower in the patients than the controls. We have documented that FD patients maintain stable CBFV during rapid BP fluctuations associated with early and late phase II and phase IV of VM suggesting that small intracerebral vessels of FD patients are less responsive to rapid systemic blood pressure fluctuations. To compensate for decreased sympathetic vascular innervation, we propose that FD patients may alter the myogenic component of CA by vessel wall thickening resulting in increased rigidity of intracerebral resistance vessels. The resulting vasoconstriction would allow maintenance of normal baseline CBFV in spite of chronic recumbent hypertension. Received: 31 August 2001, Accepted: 24 April 2002 Correspondence to M. J. Hilz, M. D., Ph. D.     

Brain luxury perfusion during cardiopulmonary bypass in humans. A study of the cerebral blood flow response to changes in CO2, O2, and blood pressure

CBF and related parameters were studied in 68 patients before, during, and following cardiopulmonary bypass. CBF was measured using the intraarterial 133Xe injection method. The extracorporeal circuit was nonpulsatile with a bubble oxygenator administering 3-5% CO2 in the main group of hypercapnic patients (n = 59) and no CO2 in a second group of hypocapnic patients. In the hypercapnic patients, marked changes in CBF occurred during bypass. Evidence was found of a brain luxury perfusion that could not be related to the effect of CO2 per se. Mean CBF was 29 ml/100 g/min just before bypass, 49 ml/100 g/min at steady-state hypothermia (27 degrees C), reached a maximum of 73 ml/100 g/min during the rewarming phase (32 degrees C), fell to 56 ml/100 g/min at steady-state normothermic bypass (37 degrees C), and was 48 ml/100 g/min shortly after bypass was stopped. Addition of CO2 evoked systemic vasodilation with low blood pressure and a rebound hyperemia. The hypocapnic group responded more physiologically to the induced changes in hematocrit (Htc) and temperature, CBF being 25, 23, 25, 34, and 35 ml/100 g/min, respectively, during the five corresponding periods. Carbon dioxide was an important regulator of CBF during all phases of cardiac surgery, the responsiveness of CBF being approximately 4% for each 1-mm Hg change of PaCO2. The level of MABP was important for the CO2 response. At low blood pressure states, the CBF responsiveness to changes in PaCO2 was almost abolished. An optimal level of PaCO2 during hypothermic bypass of approximately 25 mm Hg (at actual temperature) is recommended. A normal autoregulatory response of CBF to changes in blood pressure was found during and following bypass. The lower limit of autoregulation was at pressure levels of approximately 50-60 mm Hg. CBF autoregulation was almost abolished at PaCO2 levels of greater than 50 mm Hg. The degree of hemodilution neither affected the CO2 response nor impaired CBF autoregulation, although, as would be expected, it influenced CBF: In 33 women CBF was 55 ml/100 g/min at an Htc of 24%, as compared with 42 ml/100 g/min in 35 men (Htc = 28%). High PaO2 was a vasoconstrictor, the autoregulatory plateau being narrowed. The lower limit of autoregulation was shifted to a higher pressure when PaO2 was low.     

Global ischemia in dogs: cerebrovascular CO2 reactivity and autoregulation.

One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO2, and (2) cerebral blood (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing PACO2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant PaCO2. These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.     

Changes in human cerebral blood flow and cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography.

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 +/- 2.6%/mm Hg and 1.8 +/- 1.3%/mm Hg, respectively, and those to hypocapnia were -3.5 +/- 0.6%/mm Hg and -1.3 +/- 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09 CBF0.29. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.     

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO(2) pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (-0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (-0.23 ± 0.06 vs. -0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.     

Acute exposure to normobaric mild hypoxia alters dynamic relationships between blood pressure and cerebral blood flow at very low frequency.

Acute hypoxia directly causes cerebral arteriole vasodilation and also stimulates peripheral chemoreceptors to change autonomic neural activity. These changes may alter cerebral vascular modulation. We therefore hypothesized that dynamic cerebral autoregulation would be altered during acute exposure to hypoxia. Fifteen healthy men were examined under normoxic (21%) and hypoxic conditions. Oxygen concentrations were decreased in stepwise fashion to 19%, 17%, and 15%, for 10 mins at each level. Mean blood pressure (MBP) in the radial artery was measured via tonometry, and cerebral blood flow velocity (CBFV) in the middle cerebral artery was measured by transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis of beat-by-beat changes in MBP and CBFV. Arterial oxygen saturation decreased significantly during hypoxia, while end-tidal CO2 and respiratory rate were unchanged, as was steady-state CBFV. With 15% O2, very-low-frequency power of MBP and CBFV variability increased significantly by 185% and 282%, respectively. Moreover, transfer function coherence (21% O2, 0.46+/-0.04; 15% O2, 0.64+/-0.04; P=0.028) and gain (21% O2, 0.61+/-0.05 cm/secs/mm Hg; 15% O2, 0.86+/-0.08 cm/secs/mm Hg; P=0.035) in the very-low-frequency range increased significantly by 53% and 48% with 15% O2, respectively. However, these indices were unchanged in low- and high-frequency ranges. Acute hypoxia thus increases arterial pressure oscillations and dependence of cerebral blood flow (CBF) fluctuations on blood pressure oscillations, resulting in apparent increases in CBF fluctuations in the very-low-frequency range. Hypoxia may thus impair dynamic cerebral autoregulation in this range. However, these changes were significant only with hypoxia at 15% O2, suggesting a possible threshold for such changes.     

Influence of the endothelial glycocalyx on cerebral blood flow in mice.

The endothelial surface layer (glycocalyx) of cerebral capillaries may increase resistance to blood flow. This hypothesis was investigated in mice by intravenous administration of heparinase (2500 IU/kg body weight in saline), which cleaves proteoglycan junctions of the glycocalyx. Morphology was investigated by transmission electron microscopy. Cerebral perfusion velocity was recorded before and during heparinase or saline treatment using laser-Doppler flowmetry. In addition, cerebral blood flow (CBF) was measured 10 minutes after heparinase or saline treatment using the iodo[14C]antipyrine method. Laser-Doppler flowmetry and CBF measurements were performed during normocapnia and severe hypercapnia (PCO2: 120 mm Hg). After heparinase, morphology showed a reduced thickness of the glycocalyx in cortical microvessels by 43% (P < 0.05) compared with saline-treated controls. Under normocapnic conditions, a 15% (P < 0.05) transient increase of cerebral flow velocity occurred 2.5 to 5 minutes after heparinase injection. Laser-Doppler flow and CBF returned to control values ten minutes after the injection. However, during severe hypercapnia, heparinase treatment resulted in a persisting increase in laser-Doppler flow (6%, P < 0.05) and CBF (30%, P < 0.05). These observations indicate the existence of a flow resistance in cerebral capillaries exerted by the glycocalyx. The transient nature of the CBF increase during normocapnia may be explained by a vascular compensation that is exhausted during severe hypercapnia.     

Analysis of the effect of bilateral sympathetic stimulation of cerebral and cephalic blood flow in the dog

Unilateral stimulation of the cervical sympathetic in dogs had no effect on cerebral blood flow (CBF) measured by the venous outflow technique. Since this technique measured CBF from both cerebral hemispheres, small changes induced by unilateral stimulation could have been masked by a large constant CBF measured from the contralteral hemisphere. To test this possibility the effect of simultaneous bilateral sympathetic stimulation was studied when the dog was breathing either normal air or a gas mixture of 10%CO2. During normocapnia, no changes in CBF occurred; during hypercapnia CBF increased 19% following passively the increase in blood pressure. These data indicate that bilateral stimulation of extracranial sympathetic nerves does not exert a significant effect on CBF. We show mathematically and experimentally that unoccluded anastomses will cause CBF to appear to decrease in response to sympathetic stimulation. This may explain why others have observed changes in CBF during sympathetic stimulation.     

Endorphinergic mechanisms in cerebral blood flow autoregulation

The influence of naturally occurring opioid peptides (Met-enkephalin (Met-Enk), dynorphin (DYN), β-endorphin (β-EP)) as well as morphine and the opiate antagonist naloxone and specific antisera on cerebral blood flow autoregulation was studied in anesthetized, artificially ventillated rats. Local hypothalamic blood flow (CBF, H₂-gas clearance technique) and total cerebral blood volume (CBV, photoelectric method) were simultaneously recorded. Autoregulation was tested by determining CBF and CBV during consecutive stepwise lowering of the systemic mean arterial pressure to 80, 60 and 40 mm Hg, by hemorrhage. Resting CBF decreased following Met-Enk, DYN, β-EP or morphine administration without simultaneous changes in CBV. Naloxone administration, on the contrary, increased CBV without affecting local CBF. Autoregulation of cerebral blood flow was maintained until 80 mm Hg, but not completely at 60 and 40 mm Hg arterial pressure in the control group. General opiate receptor blockade by 1 mg/kg s.c. naloxone abolished autoregulation at all levels, since CBF and CBV passively followed the arterial pressure changes. Intracerebroventricularly injected naloxone (1 μg/kg) as well as a specific antiserum against β-EP, but not against Met-Enk or DYN, resulted in the very same effect as peripherally injected naloxone. The present findings suggest that central, periventricular β-endorphinergic mechanisms might play a major role in CBF autoregulation.