Spontaneous blood pressure oscillations and cerebral autoregulation

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

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。     

Autonomic dysfunction and impaired cerebral autoregulation in cirrhosis

Cerebral blood flow autoregulation is lost in patients with severe liver cirrhosis. The cause of this is unknown. We determined whether autonomic dysfunction was related to impaired cerebral autoregulation in patients with cirrhosis. Fourteen patients with liver cirrhosis and 11 healthy volunteers were recruited. Autonomic function was assessed in response to deep breathing, head-up tilt and during 24-h Holter monitoring. Cerebral autoregulation was assessed by determining the change in mean cerebral blood flow velocity (MCAVm, transcranial Doppler) during an increase in blood pressure induced by norepinephrine infusion (NE). The severity of liver disease was assessed using the Child–Pugh scale (class A, mild; class B, moderate; class C, severe liver dysfunction). NE increased blood pressure similarly in the controls (27 (24–32) mmHg) and patients with the most severe liver cirrhosis (Child–Pugh C, 31 (26–44) mmHg, p=0.405 Mann–Whitney). However, the increase in MCAVm was greater in cirrhosis patients compared to the controls (Child–Pugh C, 26 (24–39) %; controls, 3 (−1.3 to 3) %; respectively, p=0.016, Mann–Whitney). HRV during deep breathing was reduced in the cirrhosis patients (Child–Pugh C, 6.0±2.0 bpm) compared to the controls (21.7±2.2 bpm, p=0.001, Tukey’ test). Systolic blood pressure fell during head-up tilt only in patients with severe cirrhosis. Our results imply that cerebral autoregulation was impaired in the most severe cases of liver cirrhosis, and that those with impaired cerebral autoregulation also had severe parasympathetic and sympathetic autonomic dysfunction. Furthermore, the degree of liver dysfunction was associated with increasing severity of autonomic dysfunction. Although this association is not necessarily causal, we postulate that the loss of sympathetic innervation to the cerebral resistance vessels may contribute to the impairment of cerebral autoregulation in patients with end-stage liver disease. Financial support The study was funded by: Danish Medical Research Council. The Danish Hospital Foundation for Medical Research, Region of Copenhagen, the Faroe Islands and Greenland. Rigshospitalet. University of Copenhagen. The Laerdal Foundation for Acute Medicine. Sawmill owner Jeppe Juhl and Wife Ovita Juhls Foundation. The Novo Nordisk Foundation. The King Christian the 10th Foundation. The AP-Moeller Foundation. The Beckett Foundation.     

一种自动标记异常血压和血流速度信号的算法*

背景：目前,异常血压信号检测的主要方法是提取每个心动周期血压信号的特征,再分类识别。由于大多数血压信号是正常的,只有少数异常,如果对每个周期的信号进行检测,效率是比较低的。因此关于异常血流速度信号检测的文章不多见。 目的：基于异常信号的频域和时域特征,提出了一种自动标记异常血压和血流速度信号的算法。 方法：先从频域上筛选出可能的异常信号,再分析这些可能异常信号的时域特征,从而最终标记出所有的异常信号。 结果与结论：异常信号的标记和识别是预处理比较关键的一步,这步对后期信号分析的正确性起决定性作用。目前对于信号的异常标记大都是基于形态学分析判断,往往要遍历所有数据。先从信号的频域特征分析,删选需要判别的对象,提高了计算速度。该算法能够识别出大多数的异常信号,当然也存在一部分的错误标记信号,因为该算法的判断标准还要考虑到后期的处理需要(是否影响信号均值),所以对有些信号人为判断是较模糊的。下一步工作是希望建立异常信号的严格判断标准,并在算法的时域特征选择和判断上做进一步完善。 关键词：异常信号;血压;脑血流速度;信号算法;数字化医学     

Longitudinal relation between blood pressure,antihypertensive use and cerebral blood flow,using arterial spin labelling MRI

Consistent cerebral blood flow (CBF) is fundamental to brain function. Cerebral autoregulation ensures CBF stability. Chronic hypertension can lead to disrupted cerebral autoregulation in older people, potentially leading to blood pressure levels interfering with CBF. This study tested whether low BP and AHD use are associated with contemporaneous low CBF, and whether longitudinal change in BP is associated with change in CBF, using arterial spin labelling (ASL) MRI, in a prospective longitudinal cohort of 186 community-dwelling older individuals with hypertension (77 ± 3 years, 53% female), 125 (67%) of whom with 3-year follow-up. Diastolic blood pressure, systolic blood pressure, mean arterial pressure, and pulse pressure were assessed as blood pressure parameters. As additional cerebrovascular marker, we evaluated the ASL signal spatial coefficient of variation (ASL SCoV), a measure of ASL signal heterogeneity that may reflect cerebrovascular health. We found no associations between any of the blood pressure measures and concurrent CBF nor between changes in blood pressure measures and CBF over three-year follow-up. Antihypertensive use was associated with lower grey matter CBF (−5.49 ml/100 g/min, 95%CI = −10.7|−0.27, p = 0.04) and higher ASL SCoV (0.32 SD, 95%CI = 0.12|0.52, p = 0.002). These results warrant future research on the potential relations between antihypertensive use and cerebral perfusion.     

Autoregulation of cerebral blood flow to changes in arterial pressure in mild Alzheimer's disease

Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer''s disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent ¹⁵O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107±13 to 92±9 mm Hg with intravenous nicardipine; ¹¹C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (−0.9±5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=−3.4 to 1.5), cortical borderzones (−1.9±5.0 mL per 100 g per minute, P=0.10, 95% CI=−4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (−0.3±4.4 mL per 100 g per minute, P=0.85, 95% CI=−3.3 to 3.9), or regions of peak ¹¹C-PIB uptake (−2.5±7.7 mL per 100 g per minute, P=0.30, 95% CI=−7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD.     

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.     

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。     

Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease

Abstract. In Fabry disease, there is glycosphingolipid storage in vascular endothelial and smooth muscle cells and neurons of the autonomic nervous system. Vascular or autonomic dysfunction is likely to compromise cerebral blood flow velocities and cerebral autoregulation. This study was performed to evaluate cerebral blood flow velocities and cerebral autoregulation in Fabry patients. In 22 Fabry patients and 24 controls, we monitored resting respiratory frequency, electrocardiographic RR-intervals, blood pressure, and cerebral blood flow velocities (CBFV) in the middle cerebral artery using transcranial Doppler sonography. We assessed the Resistance Index, Pulsatility Index, Cerebrovascular Resistance, and spectral powers of oscillations in RR-intervals, mean blood pressure and mean CBFV in the high (0.15–0.5 Hz) and sympathetically mediated low frequency (0.04–0.15 Hz) ranges using autoregressive analysis. Cerebral autoregulation was determined from the transfer function gain between the low frequency oscillations in mean blood pressure and mean CBFV. Mean CBFV (P < 0.05) and the powers of mean blood pressure (P < 0.01) and mean CBFV oscillations (P < 0.05) in the low frequency range were lower,while RR-intervals, Resistance Index (P < 0.01), Pulsatility Index, Cerebrovascular Resistance (P < 0.05), and the transfer function gain between low frequency oscillations in mean blood pressure and mean CBFV (P < 0.01) were higher in patients than in controls. Mean blood pressure, respiratory frequency and spectral powers of RR-intervals did not differ between the two groups (P > 0.05). The decrease of CBFV might result from downstream stenoses of resistance vessels and dilatation of the insonated segment of the middle cerebral artery due to reduced sympathetic tone and vessel wall pathology with decreased elasticity. The augmented gain between blood pressure and CBFV oscillations indicates inability to dampen blood pressure fluctuations by cerebral autoregulation. Both, reduced CBFV and impaired cerebral autoregulation, are likely to be involved in the increased risk of stroke in patients with Fabry disease.     

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.     

Dynamic cerebral autoregulation is impaired in glaucoma

Objectives: Autonomic and endothelial dysfunction is likely to contribute to the pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma (POAG). Although there is evidence of vasomotor dysregulation with decreased peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been evaluated. The aim of our study was to assess dynamic CA in patients with NPG and POAG. Materials and Methods: In 10 NPG patients, 11 POAG patients and 11 controls, we assessed the response of cerebral blood flow velocity (CBFV) to oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz. CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz oscillations in MAP and CBFV. Results: 0.1 Hz spectral powers of MAP did not differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients with NPG (5.68±1.2 cm² s⁻²) and POAG (6.79±2.1 cm² s⁻²) than in controls (2.40±0.4 cm² s⁻²). Furthermore, the MAP–CBFV gain was higher in NPG (2.44±0.5 arbitrary units [a.u.]) and POAG (1.99±0.2 a.u.) than in controls (1.21±0.1 a.u.). Conclusion: Enhanced transmission of oscillations in MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and might contribute to an increased risk of cerebrovascular disorders in these diseases.     

Preservation of cerebral autoregulation in the unanesthetized hypoxemic newborn dog

Studies were conducted to determine the effects of hypoxemia on cerebral blood flow and the influence of hyperoxia and hypoxemia on autoregulation of cerebral blood flow in the unanesthetized newborn dog. Twenty-one newborn dogs less than 2 weeks of age were studied. Cerebral blood flow was measured using radioactive microspheres during successive periods of normotension, hypotension (produced by blood withdrawal) and normotension (produced by infusion of previously withdrawn blood). In the hyperoxic animals, arterial pO2 was maintained above 250 torr by having the animal breathe 100% oxygen, while in the hypoxemic animals arterial pO2 was maintained between 30 and 35 torr by having the animal breathe 12% O2. Cerebral blood flow increased significantly with hypoxemia. In both hypoxemic and hyperoxic animals cerebral blood flow was maintained constant in spite of a large fall in arterial blood pressure and cardiac output, demonstrating the presence of autoregulation. Calculated oxygen transport to the brain was constant during hypoxemia and hypotension in all animals. Thus autoregulation of cerebral blood flow is present in newborn animals and is preserved under conditions of moderate hypoxemia.     

The effect of metabolic acidosis upon autoregulation of cerebral blood flow in newborn dogs

The radioactive microsphere technique was used in 13 newborn dogs to determine the effect of a metabolic (lactic)acidosis upon cardiac outout (CO), cerebral blood flow (CBF), and autoregulation of cerebral blood flow. The animals were mechanically ventilated with supplemental oxygen to ensure normocarbia and hyperoxia throughout the experiments. Baseline cardiac output and cerebral blood flow measurements were made, followed by a lactic acid infusion to maintain pH < 7.25. Metabolic acidosis produced a 27% fall in cardiac output and no change in cerebral blood flow (19 ml/100 g/min). Autoregulation was tested in 6 of the acidemic puppies by acute volume depletion to reduce blood pressure by 30% of baseline, followed by rapid volume re-expansion of the withdrawn blood. With volume depletion, CO decreased by 38%, and with volume re-expansion CO returned to baseline. The CBF remained at baseline levels with volume depletion but was slightly increased after rapid volume re-expansion. Five academic controls maintained CO and CBF constant with time. Thus cerebral autoregulation is preserved in the newborn dogs during metabolic acidosis, although cerebral blood flow was slightly increased following volume re-expansion.     

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.     

Normal pressure hydrocephalus and cerebral blood flow: a review

Normal pressure hydrocephalus is a neurological disease which poses both diagnostic and therapeutic problems for the clinician. The measurement and characterisation of cerebral blood flow has been proposed as a tool for resolving such problems as well as elucidating its pathophysiology. We review the results of studies in which this tool has been applied to normal pressure hydrocephalus patients and consider the merits of the techniques that have been utilised. Finally, consideration is given to feasible future studies and the methods that could be employed in the study of cerebral blood flow and metabolism in patients with normal pressure hydrocephalus.     

Hemispheric asymmetry and temporal profiles of cerebral pressure autoregulation in head injury

A moving correlation index (Mx-ABP) between arterial blood pressure (ABP) and mean middle cerebral artery blood flow velocity (CBFV) can be used to monitor dynamic cerebrovascular autoregulation (CA) after traumatic brain injury (TBI). In this study we examined hemispheric CA asymmetry and temporal CA profiles, their relationship with ABP and CBFV, and their prognostic relevance. Mx-ABP was calculated for each hemisphere in 25 TBI patients second-daily for as long as they were receiving sedation and analgesia. Forty-nine recordings were obtained, between one and six per patient. Four time periods were defined: immediate - postinjury days (PID) 0 and 1; early - PID 2 and 3; intermediate - PID 4 and 5, and late - PID 6 and later. GOS was estimated at discharge, GOS 4 and 5 were considered favorable (15 patients) and GOS 1-3 unfavorable outcome (10 patients). A Mx difference >0.2 was classified as hemispheric asymmetry (HA). HA was observed at least once in 12 of the 25 patients (48%) and in 18 of 49 recordings (37%). It was observed during all time periods: 35%, 43%, 25%, 43%, respectively, and was not related to outcome. There was no difference in mean CBFV or ABP between patients with and without HA. HA was not related to interhemispheric CBFV differences. A significant improvement in Mx was seen over time. Hemispheric CA asymmetry is common after traumatic brain injury. It does not bear significant clinical or predictive relevance, and it is unrelated to CBFV or ABP. CA is most profoundly disturbed during the immediate postinjury phase and improves gradually during the ICU course. Further studies are needed to investigate CA during post ICU recovery and rehabilitation.     

Regulation of optic nerve head blood flow during combined changes in intraocular pressure and arterial blood pressure

In the choroid, there is evidence that blood flow does not only depend on ocular perfusion pressure (OPP), but also on absolute mean arterial pressure (MAP) and intraocular pressure (IOP). The present study included 40 healthy subjects to investigate whether such behavior is also found in the optic nerve head (ONH). The ONH blood flow (ONHBF) was studied using laser Doppler flowmetry during a separate increase in IOP and MAP as well as during a combined elevation. Mean arterial pressure was increased by isometric exercise and IOP by the suction method. During both, the change in ONHBF was less pronounced than the change in OPP indicating autoregulation. Correlation analysis was performed for the combined experiments after pooling all data according to IOP and MAP values. A correlation between ONHBF and MAP was found at IOPs ⩽25 mm Hg (P<0.001), but not at IOPs>25 mm Hg (P=0.79). Optic nerve head blood flow and IOP were significantly correlated (P<0.001), and ONHBF was only slightly dependent on MAP. The data of the present study indicate a complex regulation of ONHBF during combined changes in MAP and IOP. Our results may be compatible with myogenic mechanisms underlying autoregulation, and indicate better ONHBF regulation during an increase in MAP than during an increase in IOP.     

Aging impairs myogenic adaptation to pulsatile pressure in mouse cerebral arteries

Stability of myogenic tone in middle cerebral arteries (MCA) is essential for adequate control over penetration of pressure waves into the distal portion of the cerebral microcirculation. Because the increased pulse pressure observed in advanced aging is associated with cerebromicrovascular injury, the effect of aging on myogenic response of mouse MCAs was determined. Aging did not affect the myogenic constriction in response to static increases in pressure, whereas it significantly impaired pulsatile pressure-induced myogenic tone. Impaired myogenic adaptation of MCAs to pulsatile pressure may allow high pressure to penetrate the distal portion of the cerebral microcirculation, contributing to microvascular damage.     

Intracranial haemorrhage induced at arterial pressure in the rat: Part 2: Short term changes in local cerebral blood flow measured by autoradiography

The regional distribution of blood flow following intracranial haemorrhage at arterial pressure was measured with the ¹⁴C-iodoantipyrine autoradiographic technique in Sprague Dawley Rats. With uncontained haemorrhage, there was a bilateral reduction in cerebral blood flow, associated with a fall in cerebral perfusion pressure. With contained intracerebral haemorrhage there was a profound ipsilateral reduction in flow in the hemisphere adjacent to the haematoma. This study, indicates that extensive cerebral ischaemia occurs immediately after an intracerebral haemorrhage, and that this may be the result of compression of the microcirculation.