Cerebrospinal compensation of pulsating cerebral blood volume in hydrocephalus

Abstract

Objective: The aim of the study was to develop a computational method for the assessment of brain pressure compensation of cerebrospinal arterial blood inflow. The method was verified using clinical recordings performed during infusion studies in a group of patients diagnosed with hydrocephalus.

Materials and methods: We studied 27 patients suspected of having normal pressure hydrocephalus. The infusion test was used to measure the resistance to cerebrospinal fluid outflow, and the elastance coefficient was performed together with recording of the blood flow velocity in the middle cerebral artery. From the blood flow velocity waveform, the pulsatile pattern of increasing cerebral blood volume during one heart cycle was evaluated as a time integral of the arterial blood flow velocity minus the mean arterial blood flow. Cerebrospinal 'compliance index' (C _i) was calculated as the amplitude of change in blood volume divided by the amplitude of intracranial pressure pulse waveform.

Results: Compliance index C _i decreased during the infusion test, proportionally inverse to the rise in intracranial pressure controlled by the external infusion of saline (R=?0·76; p<0·005). A relative change in compliance (from baseline to the plateau phase of the study) was positively associated with greater brain elasticity (R=0·61; p<0·005) and poorer compensatory reserve at the phase of infusion (R=0·51; p=0·009)

Conclusion: C _i decreases during the infusion study and seems to well replicate the relative changes in cerebrospinal compensatory reserve in hydrocephalus.     

L-arginine reactivity in cerebral vessels after severe traumatic brain injury

Abstract

Objectives: Traumatic brain injury (TBI) causes an early reduction of cerebral blood flow (CBF). The purpose was to study cerebrovascular endothelial function by examining the reactivity of cerebral vessels to L-arginine.

Methods: Fifty-one patients with severe TBI were prospectively studied by measuring cerebral hemodynamics before and after the administration of L-arginine, 300 mg/kg at 12 hours and at 48 hours after injury. These hemodynamic measurements, using transcranial Doppler techniques, included internal carotid flow volume as an estimate of hemispheric CBF, flow velocity in intracranial vessels, CO₂ reactivity, and dynamic pressure autoregulation using thigh cuff deflation and carotid compression methods. Changes in the hemodynamics with L-arginine administration were analyzed using a general linear mixed model.

Results: L-arginine produced no change in mean arterial pressure, intracranial pressure, or brain oxygenation. Overall, L-arginine induced an 11.3% increase in internal carotid artery flow volume (P=0.0190). This increase was larger at 48 hours than at 12 hours (P=0.0045), and tended to be larger in the less injured hemisphere at both time periods. The response of flow velocity in the intracranial vessels was similar, but smaller differences with administration of L-arginine were observed. There was a significant improvement in CO₂ reactivity with L-arginine, but no change in dynamic pressure autoregulation.

Discussion: The low response of the cerebral vessels to L-arginine at 12 hours post-injury with improvement at 48 hours suggests that dysfunction of cerebrovascular endothelium plays a role in the reduced CBF observed after TBI.     

Impaired dynamic cerebral autoregulation in middle cerebral artery stenosis

Abstract

Background and purpose: Analysis of dynamic cerebral autoregulation during transient falls in blood pressure is considered a sensitive and convenient method for evaluating patients with carotid artery stenosis. To this point, there have been few reports on the efficacy of using the thigh cuffs technique to analyse middle cerebral artery (MCA) stenosis. If it could be determined whether cerebral blood flow can be maintained (autoregulated) during sudden falls in arterial blood pressure (ABP), then it might be possible to identify patients with MCA stenosis who are at risk of stroke.

Methods: We used the thigh cuff technique to estimate dynamic cerebral autoregulation in 57 patients with MCA stenosis and 72 normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of the rise of MCA blood velocity and compared it with the rate of the rise of arterial blood pressure. In this manner, the dynamic cerbral autoregulation of 11 patients undergoing MCA M1 stent angioplasty was estimated both pre- and post-operation.

Results: The autoregulatory index (ARI) was significantly reduced in patients with stenosed/occluded MCA (3.24 ± 1.52), as compared with normal controls (5.25 ± 1.39; p<0.001) (results reported as mean ± SD). Poor ARI values are usually observed in patients with a higher degree of stenosis and particularly in patients with insufficient collateral compensation. ARI was significantly reduced in severe stroke patients (modified ranking scale≥1), as compared with asymptomatic or TIA patients (p<0.05). After MCA stent angioplasty was performed, there was a significant improvement in ARI in 11 subjects, which caused a mean increase in ARI from 2.08 ± 1.10 to 3.80 ± 1.36 (p=0.008).

Conclusions: Dynamic cerebral autoregulation is impaired in patients with middle cerebral artery stenosis. Assessing dynamic cerebral autoregulation may allow a subgroup of patients with MCA stenosis who are at risk of hemodynamic stroke to be identified. Dynamic cerebral disautoregulation in patients with severe MCA stenosis is mostly remedied by stent angioplasty.     

Impairment of cerebral hemodynamic response to the cold pressor test in patients with Parkinson's disease

Background and purposeDisturbance of the autonomic nervous system (ANS) is frequently encountered in Parkinson's disease (PD). In this study, we examined changes in systemic and cerebral hemodynamics during the cold pressor test (CPT) to determine whether cerebrovascular reactivity, controlled by the sympathetic nervous system, is intact or impaired in patients with PD.MethodsForty-nine patients with PD and 49 sex- and age-matched non-PD subjects were evaluated. Measurements were performed in the resting state and over a period of 1 min of CPT. The cerebral blood flow velocity (CBFV) and pulsatility index (PI) of the middle cerebral artery (MCA) were recorded by transcranial color-coded Doppler ultrasonography (TCCS). Mean arterial blood pressure (MAP), heart rate (HR), and end-tidal CO₂ (Et-CO₂) were investigated simultaneously. The resistance of the cerebrovascular bed (CVR) was calculated as the ratio of mean arterial blood pressure to mean cerebral blood flow velocity (Vm). Changes of Vm, PI and CVR in response to the cold pressor test were evaluated.ResultsBaseline values for control and PD subjects showed no statistical difference. CPT induced a significant increase in MAP, HR, and Vm in both groups. Pulsatility index (PI) and CVR were decreased in both groups during CPT. Percent increases of Vm (P < 0.001) and MAP (P = 0.011) were significantly higher while the percent decreases of PI (P = 0.002) and CVR (P = 0.007) were significantly decreased more in the non-PD group.ConclusionsThis study indirectly shows that ANS-mediated cerebrovascular reactivity is impaired in patients with PD. Further investigations are needed to confirm the hypothesis that using the cold pressor test to evaluate cerebrovascular reactivity might be beneficial in early diagnosis of impairment of ANS-mediated cerebrovascular autoregulation in patients with PD.     

Effect of monoamine oxidase inhibition on the regional cerebral blood flow response to circulating noradrenaline

The effect of an acute i.v. infusion of noradrenaline (NA) on regional cerebral blood flow (rCBF) was investigated in the awake rat using [¹⁴C]iodoantipyrine as diffusible tracer. The contribution of vascular monoamine oxidase (MAO) to the efficiency of the enzymatic blood-brain barrier (BBB) to catecholamines was assessed by measuring the multiregional cerebrovascular response to circulating NA given alone or after i.v. administration of the monoamine oxidase inhibitor, clorgyline. Since i.v. infusion of NA elevates blood pressure, the influence of NA on the cerebrovascular bed was first studied by determining the relationship between rCBF and the mean arterial pressure (MAP). When the MAP was only slightly increased (to approximately 130 mm Hg), a trend to flow decrease under NA infusion was observed. Secondly, we compared the effects of NA or rCBF in animals treated or not treated with clorgyline. This was performed under moderate hypertension (within the ‘autoregulated’ range of MAP) to avoid any risk of mechanical damage to the BBB. Clorgyline administration alone did not significantly modify rCBF, but the subsequent i.v. infusion of NA induced an increase in rCBF (weighted mean 14%) in all structures investigated. The differences being statistically significant (P < 0.05) in 5 out of 13 structures by up to 20%. Compared to studies involving disruption of the morphological BBB in which plasma NA elicits a widespread important increase in blood flow, the weak cerebrovascular effects we observed provide indirect evidence for the efficiency of the BBB to catecholamines in the conscious rat within the autoregulated range of arterial pressure. Conversely, the NA-induced vasodilation obtained after inhibition of vascular MAO shows that the enzymatic BBB participates in the overall restriction of the permeability to NA, with a fairly homogeneous regional distribution.     

Effect of generalized sympathetic activation by cold pressor test on cerebral hemodynamics in diabetics with autonomic dysfunction

BACKGROUND: We examined the effects of the cold pressor test on the cerebral circulation in diabetics with autonomic dysfunction without orthostatic hypotension using transcranial Doppler. METHODS: Twenty diabetics with autonomic dysfunction and 19 age-matched healthy controls participated in the study. The mean arterial blood velocity was measured in the middle cerebral artery during the cold pressor test together with the mean arterial blood pressure. RESULTS: The mean arterial blood velocity significantly (p < 0.01) increased during the 1st, 2nd, and 3rd min of the cold pressor test by 10.6, 14.1, and 13.4%, respectively, in the control subjects and by 5.8, 7.2, and 6.8%, respectively, in the diabetics. Simultaneously, the mean arterial blood pressure significantly (p < 0.01) increased by 12, 26, and 23%, respectively, in the controls and by 9.4, 12.4 and 12.9%, respectively, in the diabetics. The increases in the mean arterial velocity as well as in the mean arterial blood pressure were significantly higher in the controls than in the diabetics (p < 0.01). The change in the mean arterial blood pressure related significantly to the change in the mean arterial blood velocity both in the controls (p < 0.01, r = 0.76) and in the diabetics (p < 0.01; r = 0.59). The slope of the regression line was significantly steeper in the controls (b = 0.42, SE = 0.05) as compared with the diabetics with autonomic dysfunction (b = 0.27, SE = 0.05; p = 0.02). Moreover, also the relative increase in the cerebrovascular resistance index was higher in the controls than in the diabetics (p < 0.05). CONCLUSION: These findings in the diabetics with autonomic neuropathy, but without orthostatic hypotension, suggest a failure in the cerebral autoregulation due to impaired cerebrovascular neurogenic control.     

Effects of topical methylene blue on cyclic GMP level,blood flow,and O2 consumption in focal cerebral ischaemia

Abstract

We hypothesized that a decrease in cyclic CMPa second messenger in the glutamate—nitric oxide pathway, would reduce oxygen consumption and improve O₂ balance in the ischaemic cerebral cortex. To test this hypothesis, a study was performed in unilateral middle cerebral artery occluded rats which were assigned to either a control or methylene blue (10^–3 m) group. Regional cerebral blood flow was determined using 14C-iodoantipyrine and regional arterial and venous O₂ saturations were determined by microspectrophotometry (n = 6). Cyclic GMP level was measured by radioimmunoassay (n = 8). Cuanylate cyclase and cyclic CMP-phosphodiesterase activities were determined in an additional set of control rats (n = 10). The cyclic CMP levels were not different between the ischaemic and contralateral areas in the control group. Compared to the cyclic CMP in the control ischaemic cortextopical methylene blue significantly decreased the cyclic CMP level by 56% in the ischaemic cortex of the methylene blue group. Ischaemia did not alter the activities of guanylate cyclase but mildly decreased cyclic GMP-phosphodiesterase. The regional cerebral blood flow and O₂ consumption in the control group were 50% and 32% lower than those in corresponding contralateral cortex. Topical methylene blue did not alter regional cerebral blood flow and O₂ consumption in the ischaemic cortex. Our data showed that cyclic CMP is not a major controller on O₂ supply or O₂ consumption in the ischaemic brain. [Neurol Res 1994; 16: 449-455]     

Preliminary experience of the estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography

OBJECTIVE: The direct calculation of cerebral perfusion pressure (CPP) as the difference between mean arterial pressure and intracranial pressure (ICP) produces a number which does not always adequately describe conditions for brain perfusion. A non-invasive method of CPP measurement has previously been reported based on waveform analysis of blood flow velocity measured in the middle cerebral artery (MCA) by transcranial Doppler. This study describes the results of clinical tests of the prototype bilateral transcranial Doppler based apparatus for non-invasive CPP measurement (nCPP). METHODS: Twenty five consecutive, paralysed, sedated, and ventilated patients with head injury were studied. Intracranial pressure (ICP) and arterial blood pressure (ABP) were monitored continuously. The left and right MCAs were insonated daily (108 measurements) using a purpose built transcranial Doppler monitor (Neuro Q(TM), Deltex Ltd, Chichester, UK) with software capable of the non-invasive estimation of CPP. Time averaged values of mean and diastolic flow velocities (FVm, FVd) and ABP were calculated. nCPP was then computed as: ABPxFVd/FVm+14. RESULTS: The absolute difference between real CPP and nCPP (daily averages) was less than 10 mm Hg in 89% of measurements and less than 13 mm Hg in 92% of measurements. The 95% confidence range for predictors was no wider than +/-12 mm Hg (n=25) for the CPP, varying from 70 to 95 mm Hg. The absolute value of side to side differences in nCPP was significantly greater (p<0.05) when CT based evidence of brain swelling was present and was also positively correlated (p<0.05) with mean ICP. CONCLUSION: The device is of potential benefit for intermittent or continuous monitoring of brain perfusion pressure in situations where the direct measurement is not available or its reliability is in question.     

Association between intracranial,arterial pulse pressure amplitudes and cerebral autoregulation in head injury patients

Abstract

Objective: To explore whether intracranial pulse pressure amplitudes relate to arterial pulse pressure amplitudes and whether correlations between time-related changes in intracranial and arterial pulse pressure amplitudes associate with indices of cerebral autoregulation.

Methods: A total of 257 continuous and simultaneous intracranial pressure (ICP), arterial blood pressure (ABP) and middle cerebral artery (MCA) blood velocity recordings were obtained 1–14 days after ictus in 76 traumatic head injury patients and analysed retrospectively. Clinical outcome was assessed using the Glasgow outcome scale (GOS). Pulse pressure amplitudes of corresponding single ICP and ABP waves were correlated in consecutive 200 wave pairs. Mean ICP, mean ABP and mean ICP wave amplitudes, and mean and systolic MCA blood flow velocities, were computed in consecutive 6 second time windows. The indices of cerebral autoregulation PRx (moving correlation between mean ICP and mean ABP), and Mx and Sx (moving correlation between mean and systolic MCA blood velocity and cerebral perfusion pressure) were calculated over 4 minute periods and averaged over each recording.

Results: Intracranial pulse pressure amplitudes were not related to arterial pulse pressure amplitudes (mean of Pearson's correlations coefficients: 0.04). Outcome was related to mean ICP, PRx and Sx (p ≤ 0.04, multiple regression analysis). Correlations between intracranial and arterial pulse pressure amplitudes were weakly related to PRx (Pearson's correlation coefficient: 0.16; p=0.01), but were not related to the indices of cerebral autoregulation Mx (Pearson's correlation coefficient: 0.07) and Sx (Pearson's correlation coefficient: 0.04).

Conclusions: In this cohort of pressure recordings, we found no evidence of a correlation between intracranial and arterial blood pressure amplitudes. The correlation appeared not to be related to the state of cerebral autoregulation, although a weak correlation was found with pressure reactivity index PRx.     

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.     

Assessment of cerebrovascular and cardiovascular responses to lower body negative pressure as a test of cerebral autoregulation

The aim of this study was to determine whether lower body negative pressure (LBNP), combined with noninvasive methods of assessing changes in systemic and cerebral vascular resistance, is suitable as a method for assessing cerebral autoregulation.In 13 subjects we continuously assessed heart rate, blood pressure, cerebral blood flow velocity (CBFV) and cardiac output during graded levels of LBNP from 0 to -50 mm Hg. With increasing levels of LBNP, cardiac output declined significantly (to 55.8+/-4.5% of baseline value) but there was no overall change in mean arterial pressure. CBFV also fell at higher levels of LBNP (to 81.4+/-3.2% of baseline) but the percentage CBFV change was significantly less than that in cardiac output (P<0.01). The maximum increase in cerebrovascular resistance (pulsatility ratio) was significantly less than that in total peripheral resistance (17+/-6% vs. 105+/-16%, P<0.01). Spectral analysis showed that the power of low-frequency oscillations in mean arterial pressure, but not CBFV, increased significantly at the -50 mm Hg level of LBNP.These results show that, even during high levels of orthostatic stress, cerebral autoregulation is preserved and continues to protect the cerebral circulation from changes in the systemic circulation. Furthermore, assessment of cardiovascular and cerebrovascular parameters during LBNP may provide a useful clinical test of cerebral autoregulation.     

Phosphodiesterase 5 inhibitor,zaprinast, selectively increases cerebral blood flow in the ischemic penumbra in the rat brain

Abstract

Background: Guanosine 3′, 5′-cyclic monophosphate (cGMP) acts as a relaxant second messenger in the cerebral vessels. cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor increases intracellular cGMP levels. This study investigated the effect of the PDE5 inhibitor on the ischemic brain.

Methods: Regional cerebral blood flow (rCBF), cGMP concentration, and infarction volume were measured in the rat middle cerebral artery occlusion model. Ten minutes after ischemia, the animals received an intravenous (i.v.) infusion of vehicle (phosphate-buffered saline), PDE5 inhibitor, zaprinast (10 mg/kg), or nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP, 100 μg/kg). rCBF was measured continuously by laser-Doppler flowmetry in the ischemic penumbra of the ischemic and contralateral sides under continuous blood pressure monitoring. cGMP concentrations were determined using the enzyme immunoassay and infarct volumes were estimated by 2,3,5-triphenyltetrazolium chloride staining.

Results: The administration of zaprinast significantly increased rCBF in the ischemic brain compared with the pre-drug control value despite the decreased mean blood pressure, whereas it did not affect rCBF in the contralateral side. The cGMP concentration was significantly higher in the ischemic cortex compared with the contralateral side. SNAP infusion increased the cGMP concentration in the bilateral cortices to a similar extent. The volume of cerebral infarction was significantly decreased by zaprinast administration.

Conclusions: The PDE5 inhibitor zaprinast may selectively increase CBF in the ischemic brain via increased cGMP levels, thus providing a new strategy against acute cerebral infarction.     

Acute hypercarbia increases the lower limit of cerebral blood flow autoregulation in a porcine model

Objectives: In the present study, our objective was to determine if hypercarbia would alter cerebral blood flow (CBF) autoregulation and reduce the ability of cerebrovascular reactivity monitoring to identify the lower limit of cerebrovascular autoregulation (LLA).

Methods: Anaesthetised juvenile pigs were assigned between two groups: normocarbia (control group, n?=?10) or hypercarbia [high carbon dioxide (CO₂) group, n?=?8]. Normocarbia subjects were maintained with an arterial CO₂ of 40?Torr, while the hypercarbia subjects had an increase of inspired CO₂ to achieve an arterial pCO₂ of >80?Torr. Gradual hypotension was induced by continuous haemorrhage from a catheter in the femoral vein, and the LLA was determined by monitoring cortical laser Doppler flux (LDF). Vascular reactivity monitoring was performed using the pressure reactivity index (PRx) and haemoglobin volume index (HVx).

Results: There were no sustained differences in ICP between groups. Autoregulation was present in both groups, despite elevation in pCO₂.The control group had an average LLA of 45?mmHg (95% CI: 43–47?mmHg) and the high CO₂ group had a LLA of 75?mmHg (95% CI: 73–77?mmHg). The detected LLA for each subject correlated with the level of pCO₂ (spearman R?=?0.8243, P?<?0.0001). Both the PRx and HVx accurately detected the LLA despite the presence of hypercarbia.

Discussion: Hypercarbia without acidosis increases the observed LLA independent of alterations in ICP. Elevations in CO₂ can impair cerebrovascular autoregulation, but if there is a sufficient increase in blood pressure above the CO₂ altered LLA, then autoregulation persists.     

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.     

Adrenergic vasoconstrictor activity in the cerebral circulation after inhibition of nitric oxide synthesis in conscious goats

The interaction between nitric oxide (NO) and adrenergic activity in the cerebral circulation was studied using conscious goats, where blood flow to one brain hemisphere (cerebral blood flow) was electromagnetically measured, and the effects of phentolamine and hexamethonium on cerebrovascular resistance were evaluated before (control) and after inhibition of NO synthesis with NW-nitro-L-arginine methyl ester (L-NAME). L-NAME (12 goats, 40 mg kg(-1) administered i.v.) reduced cerebral blood flow from 62 +/- 3 to 44 +/- 2 ml min(-1), increased mean systemic arterial pressure from 100 +/- 3 to 126 +/- 4 mm Hg, decreased heart rate from 79 +/- 5 to 50 +/- 4 beats min(-1) and increased cerebrovascular resistance from 1.63 +/- 0.08 to 2.91 +/- 0.016 mm Hg ml(-1)min(-1) (all P < 0.01). These hemodynamic variables normalized 48-72 h after L-NAME administration. Phentolamine (six goats, 1 mg), injected into the cerebral circulation. increased cerebral blood flow without changing systenic arterial pressure, but its cerebrovascular effects were augmented for about 24 h after L-NAME. The decrements in cerebrovascular resistance induced by phentolamine, in mm Hg ml(-1) min(-1), were: under control, 0.42 +/- 0.05; immediately after L-NAME, 1.38 +/- 0.09 (P < 0.01 compared with control); by about 24 h after L-NAME, 0.71 +/- 0.09 (P < 0.05 compared with control); and by about 48 h after L-NAME, 0.40 +/- 0.07 (P > 0.05 compared with control). Hexamethonium (six goats, 0.5-1 mg kg(-1) min(-1) i.v.) decreased mean systemic arterial pressure to about 75 mm Hg and caused tachycardia similarly before and after L-NAME, but the decrements in cerebrovascular resistance were augmented for about 24 h after L-NAME. The decrements in cerebrovascular resistance induced by hexamethonium, in mm Hg ml(-1).min(-1), were: under control. 0.61 +/- 0.09, immediately after L-NAME, 1.33 +/- 0.16 (P < 0.01 compared with control); by about 24 h after L-NAME, 1.18 +/- 0.10 (P < 0.01 compared with control): and by about 48 h after L-NAME, 0.99 +/- 0.10 (P > 0.05 compared with control). Therefore, these results suggest that adrenergic vasoconstrictor tone in cerebral vasculature may be augmented after inhibition of NO synthesis, and that this increment may contribute to the reduction of cerebral blood flow after inhibition of NO formation.     

Raised intracranial pressure and cerebral blood flow: 3. Venous outflow tract pressures and vascular resistances in experimental intracranial hypertension

Pressure changes within the venous outflow tract from the brain were studied in anaesthetized baboons. Segmental vascular resistance changes were also calculated and the results correlated with the changes in cerebral blood flow, measured by the ¹³³Xenon clearance method. Three different methods were used to raise intracranial pressure: cisterna magna infusion, a supratentorial subdural balloon, and an infratentorial subdural balloon. A close correlation was found between the cortical vein pressure and intracranial pressure with all methods of raising intracranial pressure: the overall correlation coefficient was 0·98. In the majority of animals sagittal sinus pressure showed little change through a wide range of intracranial pressure. In three of the six animals in the cisterna magna infusion group, however, sagittal sinus pressure increased to levels approaching the intracranial pressure during the later stages of intracranial hypertension. Jugular venous pressure showed little change with increasing intracranial pressure. The relationship between cerebral prefusion pressure and cerebral blood flow differed according to the method of increasing intracranial pressure. This was due to differing patterns of change in prevenous vascular resistance as venous resistance increased progressively with increasing pressure in all three groups. The present results confirm, therefore, the validity of the current definition of cerebral perfusion pressure—that is, cerebral perfusion pressure is equal to mean arterial pressure minus mean intracranial pressure—by demonstrating that intracranial pressure does represent the effective cerebral venous outflow pressure.     

The safety and feasibility of continuous intravenous magnesium sulfate for prevention of cerebral vasospasm in aneurysmal subarachnoid hemorrhage

Introduction: Cerebral vasospasm in aneurysmal subarachnoid hemorrhage (SAH) is associated with poor outcome. The safety and feasibility of continuous high-dose intravenous magnesium sulfate (MgSO₄) for the prevention of cerebral vasospasm and ischemic cerebral injury has not been well studied. Methods: Patients presenting to our center within 72 hours of aneurysmal SAH (confirmed by computed tomography [CT] scanning and cerebral angiography) between June 2001 and October 2002 were enrolled in a prospective pilot study in which they received MgSO₄ as an adjunct to standard SAH management. Study patients received an intravenous infusion of 12 g of MgSO₄ in a 500-mL solution of 0.9% NaCl administered at a rate of 4.06 mM (or 0.5 g) every hour over a 24-hour period for 10 days to achieve a target predetermined serum Mg range of more than 1.5 to less than 4.0 mM/L. The effect of MgSO₄ on clinical examination, heart rate, and blood pressure was measured every 2 hours; serum glucose and phenytoin levels were monitored daily. Outcome measures included evidence of vasospasm on clinical examination, transcranial Doppler study ((TCD); velocity ≥100 cm/s), or repeat cerebral angiogram obtained within 10 days of SAH; and Glasgow Outcome Scale (GOS) score assessment and CT scan evidence of ischemic infarction at 30 days. Results: Nineteen patients (mean age: 55 years; range: 39–84 years; 11 males, 8 females) were enrolled in the study. Presenting Hunt & Hess grade was II or higher; mean Fisher grade was 3. Vasospasm was observed in nine patients (by clinical examination in two, TCD in five, and angiogram in nine). The mean serum Mg level was 2.7 mM/L (standard deviation: ±0.37) and was maintained during the infusion period. No clinical adverse effects, hemodynamic changes, or fluctuations in serum glucose or phenytoin levels were observed. None of the patients died; no CT evidence of ischemic infarction was present; and most had good outcomes (GOS 5 in 10 patients; GOS 4 in 8 patients). Conclusion: Our study confirmed the safety and feasibility of a continuous infusion of high-dose intravenous MgSO₄ in patients with aneurysmal SAH. Randomized controlled trials are required to confirm the promising results.     

Carotid endarterectomy without shunt: the role of cerebral metabolic protection

Abstract

Background: The optimal method to protect the brain from hemodynamic ischemia during carotid endarterectomy (CEA) remains controversial. This study reports our experience with induced arterial hypertension and selective etomidate cerebral protection in a cohort of patients who underwent CEA without shunting and continuous electroencephalography (EEG) monitoring.

Methods: We reviewed retrospectively 102 consecutive CEAs performed in 102 patients with routine EEG monitoring and general anesthesia between March 1998 and October 2002. There were 65 (66%) symptomatic and 37 (34%) asymptomatic individuals. A protocol of induced arterial hypertension against EEG ischemic changes during carotid artery cross clamping was followed. Only patients with EEG changes refractory to induced hypertension went into etomidate-induced burst suppression.

Results: EEG changes were classified as mild, moderate and severe. Twenty patients (19.6%) developed asymmetric EEG changes, of which the great majority were mild and moderate (75%, p< 0.05). Seven patients with moderate (n=3) and severe (n=4) EEG changes needed etomidate cerebral protection. There were no mortalities and only one stroke (0.98%) is reported in the series. The morbidity rate was 6.8% and included transient cranial nerve palsies (n=5) and wound hematoma (n=1).

Conclusions: Carotid endarterectomy can be safely performed with EEG monitoring and selective induced arterial hypertension and etomidate cerebral protection. Our results suggest that this method may be a good alternative for shunting and its inherent risks.     

Influence of nimodipine on cerebral blood flow in human cerebral ischaemia

Summary Cerebral blood flow (CBF) was measured by xenon-133 inhalation and single photon emission computerized tomography (SPECT) in 7 patients with acute cerebral ischaemia prior to and 30 min after intravenous infusion of nimodipine (1 mg). Neurological examination, CT and CBF study were performed no later than 6 h after the onset of symptoms. Regional perfusion abnormalities were seen in all patients when the CT scan was still normal. Follow-up CT revealed low-density areas roughly corresponding to the core of the perfusion defect. Nimodipine infusion significantly decreased the mean arterial blood pressure (P<0.01), while PaCO₂ and clinical symptoms remained unchanged. A significant CBF improvement (P<0.05) after nimodipine was seen in the border zone of the ischaemic infarct but not in the core of the lesion or in the unaffected contralateral hemisphere.     

Intracranial pressure is a fraction of arterial blood pressure

The relation between cerebrospinal fluid pressure (p_csf) and arterial blood pressure (p_a) was studied in pigs and in rabbits before and after an ischemia-induced impairment of the cerebral autoregulation, in order to predict the effect of changes of p_a on the p_csf. Before the ischemic brain episode no clear correlation between p_a and p_csf was found. A close dependence emerged after the ischemic episode, and after each change in p_a the p_csf assumed immediately a new stationary level. The results suggest that intracranial pressure is at any moment a fraction of arterial blood pressure quantitatively determined by the coordinated action of cerebrovascular resistance, i.e. arteriolar resistance R_a, regulated by vasomotor tonus, and venous resistance R_v, which is mechanically passive in the same manner as a Starling resistor device. The relation is given by p_csf = p_a[1 + (R_a/p_v)]^?1. Induced changes in p_a have different effects on p_csf. However, this effect may be predicted to some extent because the relation between p_csf and p_a may be represented mathematically as a rectangular hyperbola. This observation may be of relevance in neurological intensive care. Changes in arterial blood pressure are known to influence intracranial pressure in patients with deranged intracranial dynamics, as in the case of severe head injury. In clinical practice, both raising systemic arterial blood pressure in order to preserve cerebral perfusion pressure and induced arterial hypotension to reduce hydrostatic capillary pressure with consequent reduction of brain edema have been used in the management of patients with severe brain injury. While theoretical models of biological systems often have a limited value in practice because of inability to measure the relevant parameters from clinical data, the ratio of cerebrovascular resistances may be calculated at the bedside.