临界关闭压对于正常大鼠脑血流自动调节的作用

目的 探讨正常大鼠脑血流自动调节范围内和超出自动调节范围后,临界关闭压（critical closing pressure,CCP）对脑血流的调控作用。 方法 健康雄性SD大鼠随机分为升压组和降压组各70只,除去手术失败的动物,完整采集数据升压 组69只,降压组54只。分别以10～15 mmHg为一级逐步升高、降低血压,同步记录大鼠大脑中动脉血 流速度（cerebral blood flow velocity,CBFV）和有创血压,绘制自动调节曲线,并按照CCP理论计算CCP 和血管面积阻力指数（resistance area product,RAP）,分析血流动力参数之间,以及血流动力学参数 与血压变化间的关系。 结果 动脉血压升高或降低过程中,正常大鼠的脑血流自动调节上、下限分别为（148.12±7.49）mmHg、 （62.96±3.34）mmHg。脑血流自动调节范围内,CBFV随动脉血压改变轻微,超出自动调节范围后,CBFV 随动脉血压升高明显增加（r =0.896,P =0.000）,或随动脉血压降低明显减小（r =0.945,P＜0.001）。 CCP变化恰好与CBFV相反,自动调节范围内随动脉血压改变明显,与平均动脉压呈明显正相关（升压 r =0.967、降压r =0.969,P均＜0.001）,超出自动调节范围后改变量明显减小。RAP也有CCP的类似趋势, 但数值变化量不是很明显,只有降压过程自动调节范围内的改变量明显大于超出自动调节范围后。 结论 大鼠脑血流调控过程中,自动调节有效范围内,脑血流的稳定与CCP和RAP密切相关,尤其是 CCP。微动脉血管紧张度和微动脉直径变化共同参与了脑血流的调控。     

脑梗死急性期患者脑血流自动调节功能观察

目的 利用临界关闭压（critical closing pressure,CCP）探讨脑梗死急性期自动调节功能及与病情的相关性。      

脑血流自动调节下限的无创测定方法研究

目的探讨脑血流自动调节下限(LLCA)的无创测定方法。方法选择青年健康志愿者32人,用经颅超声多普勒仪、无创血压监测仪监测和记录大脑中动脉的血流流速、桡动脉血压,用常规法和傅立叶变换法分别测定两组临界关闭压(CCP)和LLCA值。结果用常规法测定CCP有4例为负值,这4例经傅立叶变换法测定均为正值。常规法测定的LLCA值为(66.76±9.14)mmHg,傅立叶变换法测定的LLCA值为(60.79±10.12)mmHg,两者比较有显著性差异。结论临床无创测定LLCA宜用傅立叶变换法。     

临界关闭压对高血压大鼠脑血流的调控作用

目的 探讨临界关闭压（critical closing pressure,CCP）对肾血管性高血压大鼠（renovascular hypertensive rats,RHR）脑血流动力学改变的调控作用。方法 RHR模型（RHR组）26只,假手术正常血压对照组24只,同步记录大脑中动脉血流速度（cerebral blood flow velocity,CBFV）和有创血压,按照CCP理论计算CCP和小动脉阻力,并分析血流动力学参数之间,以及血流动力学参数与血管形态参数改变间的关系。结果 与对照组比较,RHR组动脉血压明显升高的同时,脑循环有效灌注压（effective cerebral perfusion pressure,CPPe）和血管面积阻力指数（resistance area product,RAP）明显升高（CPPe：100.80±26.40 mmHg vs 67.30±13.10 mmHg,P<0.01;RAP：2.94±0.85 vs 2.30±0.59,P=0.003）,但CBFV相对稳定,脑循环阻力（cerebral vascular resistance,CVR）升高不明显。RHR组血管面积阻力指数（resistance area product,RAP）只与小动脉管腔内径呈负相关（rs=-0.610,P=0.001）,CCP与小动脉中膜厚度呈正相关（rs=0.554,P=0.006）;而CVR不仅与小动脉管腔内径呈负相关（rs=-0.463,P=0.023）,也与小动脉中膜厚度呈正相关（rs=0.678,P＜0.01）。结论 RHR的脑血流调控可通过CCP和RAP的改变来完成,用CCP和RAP代替CVR,能更加真实、客观地反映脑血流动力学的调控机制。     

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。     

特发性高颅压患者脑血流自动调节研究

目的 分析特发性颅内压增高（idiopathic intracranial hypertension，IIH）患者脑血流自动调节机能。
方法 连续入组2018年12月-2019年3月在首都医科大学附属北京天坛医院就诊的IIH患者，并选取年
龄匹配的健康志愿者作为对照组。应用传递函数的算法分析TCD显示的大脑中动脉血流速度及动脉
血压的自然波动以评估脑血流自动调节机能。
结果 入组IIH组10例，对照组13例。所有入组者均完成了双侧大脑半球的脑血流自动调节检测，共
检测了20个高颅压半球及26个正常对照半球。与对照组相比，IIH组大脑中动脉脑血流增益显著降
低[（0.64±0.35）%/% vs（0.37%±0.20）%/%，P =0.004]；相位也显著降低（58.80±20.86°vs
39.16±23.79°，P =0.005），差异有统计学意义。IIH组每秒钟脑血流速度的恢复率较对照更低，但差
异尚未达到统计学意义（[ 26.34±43.29）%/s vs（38.81±20.16）%/s，P=0.240]。
结论 IIH患者脑血流自动调节机能显著受损。     

脑血流自动调节范围内维持脑血流恒定的因素

目的探讨脑血流自动调节范围内稳定脑血流速度的血流动力学因素。方法利用经颅多普勒检测SD大鼠大脑中动脉的血流速度(cerebral blood flow velocity,CBFV),并同步记录有创动脉血压,绘制自动调节曲线,判断脑血流自动调节上、下限。计算临界关闭压(critical closing pressure,CCP)和血管面积阻力指数(resistance area product,RAP)。分析CCP、RAP与平均动脉压(mean artery blood pressure,MABP)之间的关系。结果动脉血压升高或降低过程中,正常大鼠脑血流自动调节上、下限分别为148.12±7.49 mm Hg、62.96±3.34 mm Hg。脑血流自动调节范围内,CBFV随动脉血压改变轻微(每10 mm Hg MABP,升压:0.65±0.27 cm/s;降压:0.43±0.23 cm/s),而CCP和RAP则随动脉血压明显改变(每10 mm Hg MABP,升压:4.60±1.06 mm Hg、0.11±0.04mm Hg;降压:6.74±0.59 mm Hg、0.09±0.02 mm Hg)。虽然CBFV、CCP、RAP的变化都与MABP相关,但控制CBFV的变动后,CCP和RAP随MABP改变相关性更加明显,其中CCP的变化幅度以及与MABP的相关性明显大于RAP(升压:Beta=0.561、0.418;降压:Beta=0.694、0.266,P均=0.000)。结论大鼠脑血流自动调节有效范围内,脑血流的稳定主要通过CCP和RAP改变对抗动脉血压的变动而实现,尤其是CCP相应升高或降低。     

脑血流自动调节监测在脑血管疾病中的临床应用

脑血流自动调节（cerebral autoregulation,CA）是指脑血流在动脉血压（arterial blood pressure,ABP）和脑灌注压（cerebral perfusion pressure,CPP）发生改变时保持相对稳定的能力。临床主要通过改变血压后测量脑血流的变化以反映CA的方式很多,常用的有：下肢负压、冷加压试验、Valsalva动作等。通过改变脑灌注压来评估CA能力主要由经颅多普勒超声（transcranial Doppler,TCD）来实现,它是在生理和病理情况下测定脑血流速度和CA的有效工具,它结合体位改变对脑血流进行测量是一种更方便、更易接受的方法,对缺血性脑血管病的预后评估起到重要作用。本文就CA监测在脑血管疾病中的临床应用做一综述。     

Takayasu氏动脉炎的脑血流动力学改变

目的Takayasu氏动脉炎是主动脉及其主要分支的炎性血管病变,本研究用经颅超声多普勒(TCD)探测16例大动脉炎患者脑血流动力学的特征性改变。方法16例患者均行TCD检测,分析其收缩期血流速度(Vs)、舒张期血流速度(Vd)、脉动指数(PI)、频谱形态等改变,5例患者同时行主动脉造影。结果累及主动脉弓多支血管者,TCD表现为Willis环主干血管的Vd升高(P<0.05和P<0.01),PI均降低(P<0.001),频谱表现为波型衰减、波峰变钝、峰值后移,呈几乎无波动的频谱改变;累及主动脉弓单支血管者,TCD仅表现为锁骨下动脉狭窄伴颈内动脉及椎动脉、基底动脉分叉处狭窄。结论TCD检测显示颅内出现异常的血流动力学改变,即Vd升高、PI明显减低或锁骨下动脉狭窄、频谱出现特征性的改变等,结合临床即可诊断为Takayasu氏动脉炎。     

颅内压增高及甘露醇治疗者的脑血流动力学变化

目的：研究颅内压增高患者的脑血液动力学变化特征，并探讨TCD和甘露醇对患者的诊断治疗作用。方法：对40例颅内压增高患者进行TCD检测，其中15例行甘露醇治疗前动态观察。结果：颅内压增高患者脑血流速度（Vd,Vs）减慢，血管阻力参数值（PI，RI）增大，甘露醇治疗后检测在数明显改善，并以舒张期速及脉动指数为著，结论：根据脑血流动力学的特征性改变，结合试验性甘露醇治疗，TCD为无创性诊断和动态观察内压增高提供了依据。     

Dynamics of cerebral blood flow autoregulation in hypertensive patients

In hypertensive patients, the upper and lower limits of cerebral autoregulation are shifted to higher levels. However, the dynamics of cerebral autoregulation in hypertensive patients are less well known. We compared the dynamics of cerebral autoregulation in 21 treated hypertensive patients (13 men and 8 women; mean age: 48.9+/-13.6 years) and in 21 normotensive subjects (13 men and 8 women; mean age: 51+/-14.5 years) by transcranial Doppler (TCD) of the middle cerebral artery (MCA) during the acute decrease in blood pressure induced by standing up after 2 min in squatting position. MCA maximal outline blood flow velocity (FV), blood pressure (Finapres) and end-tidal PCO2 were continuously monitored and computerised. A cerebral vascular resistance index (CR) was calculated as follows: mean arterial BP/MCA mean FV with normalised changes in CR per second during the blood pressure decrease (CR slope). The CR slope reflecting the rate of cerebral autoregulation did not differ between the two groups and within the hypertensive patients [well controlled (8 patients) and not controlled (13 patients)]. The time to maximum decrease of CR (T1) and the time to full recovery of CR after the initial drop (T2) were also similar in the two groups (controls T1: 11.3+/-3.1 s, T2: 12+/-5.9 s; hypertensive T1: 11.7+/-2.5 s, T2: 10.7+/-4.5 s) and within hypertensive patients. These findings suggest that the dynamics of cerebral autoregulation are well preserved in hypertensive patients, with no difference according to the efficiency of treatment of hypertension.     

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.     

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.     

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 critical closing pressure and resistance-area product: the influence of dynamic cerebral autoregulation,age and sex

Instantaneous arterial pressure-flow (or velocity) relationships indicate the existence of a cerebral critical closing pressure (CrCP), with the slope of the relationship expressed by the resistance-area product (RAP). In 194 healthy subjects (20–82 years, 90 female), cerebral blood flow velocity (CBFV, transcranial Doppler), arterial blood pressure (BP, Finapres) and end-tidal CO₂ (EtCO₂, capnography) were measured continuously for five minutes during spontaneous fluctuations of BP at rest. The dynamic cerebral autoregulation (CA) index (ARI) was extracted with transfer function analysis from the CBFV step response to the BP input and step responses were also obtained for the BP-CrCP and BP-RAP relationships. ARI was shown to decrease with age at a rate of −0.025 units/year in men (p = 0.022), but not in women (p = 0.40). The temporal patterns of the BP-CBFV, BP-CrCP and BP-RAP step responses were strongly influenced by the ARI (p < 0.0001), but not by sex. Age was also a significant determinant of the peak of the CBFV step response and the tail of the RAP response. Whilst the RAP step response pattern is consistent with a myogenic mechanism controlling dynamic CA, further work is needed to explore the potential association of the CrCP step response with the flow-mediated component of autoregulation.     

Detection of impaired cerebral autoregulation improves by increasing arterial blood pressure variability

Although the assessment of dynamic cerebral autoregulation (CA) based on measurements of spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF) is a convenient and much used method, there remains uncertainty about its reliability. We tested the effects of increasing ABP variability, provoked by a modification of the thigh cuff method, on the ability of the autoregulation index to discriminate between normal and impaired CA, using hypercapnia as a surrogate for dynamic CA impairment. In 30 healthy volunteers, ABP (Finapres) and CBF velocity (CBFV, transcranial Doppler) were recorded at rest and during 5% CO₂ breathing, with and without pseudo-random sequence inflation and deflation of bilateral thigh cuffs. The application of thigh cuffs increased ABP and CBFV variabilities and was not associated with a distortion of the CBFV step response estimates for both normocapnic and hypercapnic conditions (P=0.59 and P=0.96, respectively). Sensitivity and specificity of CA impairment detection were improved with the thigh cuff method, with the area under the receiver–operator curve increasing from 0.746 to 0.859 (P=0.031). We conclude that the new method is a safe, efficient, and appealing alternative to currently existing assessment methods for the investigation of the status of CA.     

Increasing pressure of external counterpulsation augments blood pressure but not cerebral blood flow velocity in ischemic stroke

External counterpulsation (ECP) is a noninvasive method used to augment cerebral perfusion but the optimal use of ECP in ischemic stroke has not been well documented. We aimed to investigate the effects of ECP treatment pressure on cerebral blood flow and blood pressure (BP). We recruited 38 ischemic stroke patients with large artery occlusive disease and 20 elderly controls. We commenced ECP treatment pressure at 150 mmHg and gradually increased to 187.5, 225 and 262.5 mmHg. Mean cerebral blood flow velocities (CBFV) of bilateral middle cerebral arteries and continuous beat-to-beat BP were recorded before ECP and during each pressure increment for 3 minutes. Patient CBFV data was analyzed based on whether it was ipsilateral or contralateral to the infarct. Mean BP significantly increased from baseline in both stroke and control groups after ECP commenced. BP increased in both groups following raised ECP pressure and reached maximum at 262.5 mmHg (patients 16.9% increase versus controls 16.52%). The ipsilateral CBFV of patients increased 5.15%, 4.35%, 4.55% and 3.52% from baseline under the four pressures, respectively. All were significantly higher than baseline but did not differ among different ECP pressures; contralateral CBFV changed likewise. Control CBFV did not increase under variable pressures of ECP. ECP did increase CBFV of our patients to a roughly equal degree regardless of ECP pressure. Among the four ECP pressures tested, we recommend 150 mmHg as the optimal treatment pressure for ischemic stroke due to higher risks of hypertension-related complications with higher pressures.