临界关闭压在脑血流动力学评价中的应用

目的探讨检测脑血流动力学的快捷、实用的新方法,为临床检测奠定基础。方法利用经颅多普勒(TCD)检测大鼠大脑中动脉(MCA)的血流速度,同步记录有创血压,按照临界关闭压(CCP)的理论计算出脑血流自动调节的下限和微动脉阻力,与改变血压测定的结果进行比较。结果CCP法检测到的脑血流自动调节下限为70.88±24.05mmHg,与常用血压改变测定的结果数值接近,可以相互替代。肾血管性高血压大鼠(RHR)的脑血流自动调节下限和微动脉阻力的升高,与动脉血压的升高,特别是脉压差的增大密切相关。结论按照CCP理论测定脑血流自动调节下限和微动脉的阻力,可以准确、快捷地反映脑血流动力学的生理状态和病理改变。     

Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network

Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) the Cerebral Autoregulation Research Network (CARNet – www.car-net.org).     

脑血流自动调节功能的临界关闭压测定

目的探讨测定脑血流自动调节下限(LLCA)的新方法,为LLCA的广泛临床测定奠定基础。方法同步监测正常健康志愿者正常呼吸、屏气和过度换气时的大脑中动脉血流、桡动脉血压和呼气终末呼出气体CO2分压(ETco2),然后离线计算临界关闭压(CCP)和LLCA。结果正常呼吸情况下LLCA为(58.42±10.40)mmHg,屏气时LLCA明显上升(P<0.05),过度换气时明显下降(P<0.05),且都和正常呼吸时的结果高度相关(r=0.6740、0.6429,P<0.05)。与正常呼吸相比,屏气和过度换气时LLCA测定差异的95%CI分别为(8.28￣13.68)mmHg和(-16.56￣-12.20)mmHg。屏气和过度换气时LLCA的变化率与CCP的变化率均呈负相关(r=-0.6105、-0.5551,P<0.05)。结论利用CCP可准确无创地测定人类LLCA。     

Comparison of frequency and time domain methods of assessment of cerebral autoregulation in traumatic brain injury

The impulse response (IR)-based autoregulation index (ARI) allows for continuous monitoring of cerebral autoregulation using spontaneous fluctuations of arterial blood pressure (ABP) and cerebral flow velocity (FV). We compared three methods of autoregulation assessment in 288 traumatic brain injury (TBI) patients managed in the Neurocritical Care Unit: (1) IR-based ARI; (2) transfer function (TF) phase, gain, and coherence; and (3) mean flow index (Mx). Autoregulation index was calculated using the TF estimation (Welch method) and classified according to the original Tiecks'' model. Mx was calculated as a correlation coefficient between 10-second averages of ABP and FV using a moving 300-second data window. Transfer function phase, gain, and coherence were extracted in the very low frequency (VLF, 0 to 0.05 Hz) and low frequency (LF, 0.05 to 0.15 Hz) bandwidths. We studied the relationship between these parameters and also compared them with patients'' Glasgow outcome score. The calculations were performed using both cerebral perfusion pressure (CPP; suffix ‘c'') as input and ABP (suffix ‘a''). The result showed a significant relationship between ARI and Mx when using either ABP (r=−0.38, P<0.001) or CPP (r=−0.404, P<0.001) as input. Transfer function phase and coherence_a were significantly correlated with ARI_a and ARI_c (P<0.05). Only ARI_a, ARI_c, Mx_a, Mx_c, and phase_c were significantly correlated with patients'' outcome, with Mx_c showing the strongest association.     

Impaired dynamic cerebral autoregulation is associated with the severity of neuroimaging features of cerebral small vessel disease

AimsCerebral small vessel disease (CSVD) is characterized by functional and structural changes in small vessels. We aimed to elucidate the relationship between dynamic cerebral autoregulation (dCA) and neuroimaging characteristics of CSVD.MethodsA case‐control study was performed. Cerebral blood flow velocity (CBFV) of bilateral middle cerebral arteries and spontaneous arterial blood pressure were simultaneously recorded. Transfer function analysis was used to calculate dCA parameters (phase, gain, and the rate of recovery of CBFV [RoRc]). Neuroimaging characteristics of CSVD patients were evaluated, including lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), perivascular spaces (PVS), and the total CSVD burden.ResultsOverall, 113 patients and 83 controls were enrolled. Compared with the control group, the phase at low frequency and the RoRc in CSVD patients were lower, and the gain at very low and low frequencies were higher, indicating bilaterally impaired dCA. Total CSVD burden, WMH (total, periventricular and deep), severe PVS, and lobar CMBs were independently correlated with the phase at low frequency.ConclusionsOur findings suggested that dCA was compromised in CSVD patients, and some specific neuroimaging characteristics (the total CSVD burden, WMH, severe PVS and lobar CMBs) might indicate more severe dCA impairment in CSVD patients.     

Change in cerebral autoregulation as a function of time in children after severe traumatic brain injury: a case series

Objective The objective of this study was to describe changes in cerebral autoregulation after severe pediatric traumatic brain injury (TBI). Materials and methods Two cerebral autoregulation tests were performed during the first 10 days after severe TBI in children <16 years. Cerebral autoregulation was quantified using the mean autoregulatory index (mARI). Results Nine (five males/four females) children (10 ± 5 years) with severe (admission Glasgow Coma Scale (GCS), 5 ± 2) TBI were enrolled. Thirty (3/9) percent of initial exams revealed impaired cerebral autoregulation; all three had returned to intact cerebral autoregulation on second exam. However, in three of nine (33%) patients, cerebral autoregulation worsened on second exam. Of the factors examined, worsening mARI on second exam was associated with worsening head computed tomography (CT) lesion. Conclusions Cerebral autoregulation often changed and worsened during the first 9 days after severe pediatric TBI. Worsening cerebral autoregulation may mirror worsening TBI.     

Point/counterpoint: We should not take the direction of blood pressure change into consideration for dynamic cerebral autoregulation quantification

Over the past years, a wide range of studies have provided evidence of asymmetry in the response of static and dynamic cerebral autoregulation (CA) during increasing and decreasing pressure challenges. The main message is that CA is stronger during transient increases of arterial blood pressure rather than decreases. Here we do not argue against the presence of CA asymmetry but we seek to raise questions regarding the measurement of the effect and whether this effect needs to be taken into account, especially in clinical settings.     

易卒中型肾血管性高血压大鼠的脑血流自动调节下限与最低耐受压

目的　研究易卒中型肾血管性高血压大鼠 (RHRSP)的脑血流 (CBF)自动调节下限及其最低耐受压。　　方法　用氢清除法测定RHRSP和正常SD大鼠在不同低血压水平时 ,一侧顶枕交界区皮质和海马的局部CBF(rCBF) ;72小时后计算RHRSP和SD大鼠海马CA1 区神经细胞 (CA1 NC)线粒体的体密度 (Vv)、比表面 (δ)、平均体积 ( V)和数密度 (Nv) ,　　 结果　正常SD大鼠在平均动脉压 (MABP)为 1 0 67kPa、9 3 3kPa和 8kPa时 ,rCBF值无显著减少。在MABP为 1 0 67kPa时 ,RHRSP的rCBF值显著减少 ;超微结构观察发现CA1 NC无明显缺血改变 ,当MABP为 9 3 3kPa时 ,CA1 NC缺血明显 ;细胞形态分析发现 9 3 3kPa组与 1 0 67kPa组比较 ,前者线粒体的Vv和 V显著增大 ,δ和Nv显著减小。　　结论　RHRSP的CBF自动调节下限上移至 1 0 67kPa,并与其最低耐受压十分接近 ,表明RHRSP是一种研究高血压脑血管损害较理想的动物模型     

Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs

Cerebral blood flow and cerebral oxygen uptake were studied during severe arterial hypoxia in anesthetized dogs. It was shown that the hypoxic vasodilatation in the brain reaches a limit at an arterial oxygen saturation at about 25% and that this vasodilatation is less than that which may be induced by hypercapnia. A further deepening of the arterial hypoxia at a maintained cerebral perfusion pressure is combined with a continuous decrease in cerebral venous oxygen tension and a reduced oxygen uptake.     

Bradykinin antagonist counteracts the acute effect of both angiotensin-converting enzyme inhibition and of angiotensin receptor blockade on the lower limit of autoregulation of cerebral blood flow

The lower limit of autoregulation of cerebral blood flow (CBF) can be modulated with both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The influence of bradykinin antagonism on ARB-induced changes was the subject of this study. CBF was measured in Sprague–Dawley rats with laser Doppler technique. The blood pressure was lowered by controlled bleeding. Six groups of rats were studied: a control group and five groups given drugs intravenously: an ACE inhibitor (enalaprilat), an ARB (candesartan), a bradykinin-2 receptor antagonist (Hoe 140), a combination of enalaprilat and Hoe 140, and a combination of candesartan and Hoe 140. In the control group, the lower limit of CBF autoregulation was 54±9 mm Hg (mean±s.d.), with enalaprilat it was 46±6, with candesartan 39±8, with Hoe 140 53±6, with enalaprilat/Hoe 140 52±6, and with candesartan/Hoe 140 50±7. Both enalaprilat and candesartan lowered the lower limit of autoregulation of CBF significantly. The bradykinin antagonist abolished not only the effect of the ACE inhibitor but surprisingly also the effect of the ARB on the lower limit of CBF autoregulation, the latter suggesting an effect on intravascular bradykinin.     

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

Abstract

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

Influence of blood pressure and cardiac output on cerebral blood flow and autoregulation in acute stroke measured by TCD

Although the dependence of cerebral perfusion on blood pressure has been well studied, little data is available about the effect cardiac output has on cerebral flow velocity and autoregulation, particularly during acute stroke. To improve cerebral perfusion, we treated 10 patients who suffered from an acute ischemic stroke of the middle cerebral artery with a hypervolemic hemodilution combined with dopamine-dobutamine. The influence of blood pressure and cardiac output on the blood flow velocity in the middle cerebral artery was measured using transcranial doppler sonography (TCD). Under the therapy, a dosage-dependent increase of 12% in blood pressure (BP) and 53% increase in cardiac output was observed. There was a significant (p > 0.01) correlation between TCD-mean flow velocity (V_m) and cardiac output (r = 0.33) as well as between V_m and blood pressure (r = 0.52) on the affected side. The unaffected side showed no correlation between V_m and cardiac output (r = 0.01), or between V_m and blood pressure (r = 0.03). Systolic flow velocity increased significantly in both hemispheres. As an expression of increasing cerebral vascular resistance, the pulsating index (PI) increased significantly (p > 0.01) in the affected hemisphere as well as in the unaffected hemisphere. This suggests that during acute stroke blood flow velocity and autoregulation in the affected vascular region depend not only on cerebral perfusion pressure but also on CO levels.     

Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen and intracranial pressure during and after severe prolonged arterial hypoxia in dogs. The role of dopamine in the deep hypoxic state

The effect of extreme, prolonged arterial hypoxia on cerebral blood flow, oxygen uptake and intracranial pressure was studied in anesthetized dogs. The experiments were performed along two lines. Both started with a period of hypoxia of about 40 minutes to 2 hours. Thereafter normoxia was restituted in one group and the animals were studied for another 1-2 hours. In the other group with continued hypoxia dopamine was administered. During the hypoxic period the cerebral blood flow decreased mainly as a result of vasoconstriction after an initial marked flow increase. Cerebral oxygen uptake was reduced. Intracranial pressure increased, largely in proportion to blood flow changes, and no indication of important brain edema appeared. In the "recovery" period at normoxia the cerebral oxygen uptake showed an increase during the observation time. The blood flow, initially high, returned to the control level within the observation period. Dopamine infusion during continued hypoxia induced a vasodilatation, with reduction of vascular resistance to the values found at the induction of hypoxia, and with an increase of the cerebral oxygen uptake. An important role of endogenous dopamine in the hypoxic vasodilatation is suggested.     

Cerebral hemodynamic response induced by the Tower of Hanoi puzzle and the Wisconsin Card Sorting test

Transcranial Doppler sonography (TCD) was applied in normal subjects to investigate the effect of prefrontal functions like the Tower of Hanoi (TOH) task and the Wisconsin Card Sorting test (WCST) on cerebral hemodynamics. In 20 healthy volunteers, left and right middle cerebral artery (MCA) and anterior cerebral artery (ACA) were insonated. The TOH task and the WCST were administered while cerebral blood flow velocity (CBFV) was registered. Each test was repeated once per artery pair. There was a visuomotor test to control the motor and visual stimulations. Three phases of CBFV time course were detected: an initial peak within 5 s, a following decrease within 25 s and a steady state beginning at 40 s. The TOH task, WCST and visuomotor tests had different mean CBFV during the initial peak (MCA: P<0.05; ACA: P<0.05) as well as for the decrease (ACA: P<0.01) and the steady state (MCA: P<0.01; ACA: P<0.01). The TOH showed an increased mean CBFV as compared with the WCST during the steady state (MCA: P<0.01; ACA: P<0.05). However, temporal modulation of mean CBFV during category shift of the WCST resulted in significantly increased values after category shift (MCA: P<0.001; ACA: P<0.01) as compared with CBFV before the category shift. These findings showed a different CBFV pattern during the TOH task and WCST than during the visuomotor test. In conclusion, TCD was able to assess CBFV in prefrontal functions, using a high resolution in time.     

An experimental study on the effects of DMSO and indomethacin on cerebral circulation and intracranial pressure

Albino rabbits with a cryogenic lesion to the left parieto-occipital cortex had cerebral blood flow studies (CBF) with the hydrogen clearance technique 24 hours after the insult. Similar subgroups were treated with DMSO (1 g/kg) bolus, DMSO (2 g/kg) infusion, indomethacin (20 mg/kg) bolus, and indomethacin followed by DMSO. Following DMSO bolus administration there was an immediate rise in CBF over both hemispheres, with a significant paradoxical decrease at 30 minutes, followed by a second smaller rise at 60 minutes. With DMSO infusion, the rise in CBF was sustained throughout the infusion period with no paradoxical decrease. With indomethacin there was an initial decrease immediately following the drug, and at 60 minutes there was a rise in the insulted left hemisphere, more than the right one. Indomethacin administration 15 minutes prior to DMSO failed to halt the immediate increase in CBF noted following DMSO bolus injection. These results, together with the changes that occurred in intracranial pressure and brain water content, are analyzed.     

Principles of cerebral oxygenation and blood flow in the neurological critical care unit

Cerebrovascular disease and trauma are leading causes of death in the United States. In addition to the initial insult to the brain, disturbances of cerebral oxygenation and metabolism underlie many of the secondary pathophysiological processes that increase both morbidity and mortality. Therefore, researchers and clinicians have sought to obtain a more thorough understanding of the physiological and biochemical principles of cerebral oxygenation and metabolism. New technologies capable of offering continuous and quantitative assessment of cerebral oxygenation may improve clinical outcomes. In this article, we review the physiological principles of cerebral metabolism, cerebral blood flow and their metabolic coupling, and cerebral oxygenation, with particular emphasis on variables that could be monitored and managed in an intensive care unit setting. BWH Neurosurgery Group in alphabetical order are Ian F. Dunn, Dilantha B. Ellegala, Jonathan F. Fox, and Dong H. Kim.     

Use of middle cerebral velocity and blood pressure for the analysis of cerebral autoregulation at various frequencies: The coherence index

Abstract

A common component in many protocols for the evaluation ofcerebral autoregulation is the comparison of transcranial Doppler ultrasound (TCD) velocities with blood pressure recordings, in which correlations between these two signals correspond to impaired autoregulation. With long data sets and complicated paradigms, however, visual inspection alone cannot adequately distinguish random coincidence from consistent correlation in a statistically valid fashion. We suggest and illustrate the use. of the coherence index for this purpose. To illustrate this technique, long-term recordings of TCD velocity and blood pressure were obtained from 6 normal subjects and using 23 data segments from 8 patients following subarachnoid hemorrhage. Each signal was first normalized to its mean, and coherence calculated by dividing the data into qverlapping subintervals and computing an average. Coherence was specifically examined over time periods of 30 sec. Coherence calculations identified correlations between signals for which interpretation by visual inspection was unclear, and obvious correlations could be quantified. In 4 of the 6 normal subjects, the coherence was less than 0.60 but slightly greater than o. Five of the 8 patients showed segments with coherence of greater than 0.60. The coherence index provides a quantitative toot for the evaluation of comparisons between two complex signals. As this .task becomes more common in the evaluation of cerebral autoregulation, algorithms of this sort will become increasingly necessary. [Neural Res 1997; 19: 634-640]     

Microsphere analysis of local cerebral and extracerebral blood flow after complete ischemia of the cat brain for one hour

Summary In normothermic anesthetized cats complete cerebral circulatory arrest for one h was produced and followed by blood recirculation of the brain for 30 min to 4h. Total and local blood flow of the brain, kidney, heart and liver were measured before and after ischemia using radioactive labelled microspheres. Before ischemia blood flow of the brain was 39.1±2.3 ml/100 g/min, of the kidney 307.2±28.3 ml/100 g/min, of the heart 241.1±32.5 ml/100 g/min and of the liver 87.8±25.6 ml/100 g/min (means±SEM). Regional flow rates within the brain varied between 35 and 51 ml/100 g/min.Reactive hyperemia was present in the brain 30 min after the beginning of recirculation following ischemia for 1h. Local cerebral flow rates increased three to five times above the control flow, depending on the respective region. Mean cerebral blood flow returned to or slightly below normal, 2 to 4h after ischemia, but there was considerable redistribution of flow rates within the brain. The filter capacity of the brain for microspheres of 15 and 50 diameter did not change after ischemia indicating that postischemic blood recirculation was not accompanied by an opening of arteriovenous shunts.This work was supported by the Deutsche Forschungsgemeinschaft     

Correlation between the clinical picture,the EEG and cerebral blood flow after partial occlusion of the middle cerebral artery in man

Summary Quantitative measurements of global and regional cerebral blood flow were performed in 18 patients 1 to 3 days after the onset of symptoms of acute cerebral ischemia due to partial occlusion of the middle cerebral artery and were repeated 21 days thereafter. The first rCBF measurement revealed either an extensive ischemic focus or an ischemic focus with simultaneous reduction of the global blood flow within the corresponding hemisphere in all patients. The later measurements indicated no change in blood flow in the ischemic focus in any case, but there was a slight increase of global cerebral blood flow in 1/3 of the cases.The measurements of cerebral blood flow were correlated with the neurological, psychopathological and EEG findings and in spite of an unaltered cerebral blood circulation, all patients showed a distinct clinical improvement. Various hypotheses for the return of neurological functions in patients with persistent cerebral ischemia are discussed.Paper read at the Kongress der Deutschen Gesellschaft für Neurologie, Hamburg 1975