Static Cerebral Autoregulation Research Articles

TCD assessment in fulminant hepatic failure: Improvements in cerebral autoregulation after liver transplantation

Introduction and ObjectivesAcute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. Patients and MethodsThe mean age was 33.8 years (range 14–56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). ResultsCA was assessed based on the static CA index (SCAI), reflecting the effects of a 20–30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). ConclusionsThese results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48–72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.

Ambulatory Monitoring of Cerebrovascular Responses to Upright Posture and Walking in Older Adults With Heart Failure

BackgroundInsufficient cardiac output in individuals with heart failure (HF) limits daily functioning and reduces quality of life. Although lower cerebral perfusion, secondary to limitations in cardiac output, has been observed during moderate-intensity efforts, individuals with HF also may be at risk for lower perfusion during even low-intensity ambulatory activities. MethodsWe determined whether HF is associated with an altered cerebrovascular response to low-intensity activities representative of typical challenges of daily living. In this study, we monitored central hemodynamics and middle cerebral artery blood velocity (MCAv) and cerebral tissue oxygenation (near-infrared spectroscopy) in 10 individuals with HF (aged 78 ± 4 years; left ventricular ejection fraction 20%-61%) and 13 similar-aged controls (79 ± 8 years; 52%–73%) during 3 randomized transitions, as follows: (i) supine-to-standing; (ii) sitting-to-slow-paced over-ground walking; and (iii) sitting-to-normal-paced over-ground walking. ResultsThroughout supine, sitting, standing, and both walking conditions, individuals with HF had lower cardiac index and cerebral tissue oxygenation than controls (P < 0.05), and MCAv was lower across the range of blood pressure in HF patients (P = 0.051) and during walking only (P = 0.011). Individuals with HF had an attenuated increase in stroke volume index and cardiac index during normal-paced walking, compared to controls (P < 0.01). ConclusionsThe indices of cerebral perfusion from MCAv and cerebral oxygenation were lower during ambulatory activities in individuals with HF; however, relationships between MCAv and blood pressure were not different between those with HF and controls, indicating no difference in static cerebral autoregulation.

Critical Care Experience With Clinical Cerebral Autoregulation Testing in Adults With Traumatic Brain Injury.

To describe the setting, feasibility, and safety of static cerebral autoregulation testing in critically injured adults with traumatic brain injury (TBI). Methods: We reviewed static autoregulation testing using transcranial Doppler (TCD) ultrasound in patients > 18 years with TBI ICD codes between January 1, 2014, and December 31, 2021. Adverse events during testing were defined as systemic hypertension (systolic blood pressure (SBP>180 mmHg), bradycardia (HR<40 bpm), and high ICP (>30 mmHg). Impaired and absent cerebral autoregulation was defined as an autoregulatory index (ARI) <0.4 and ARI 0, respectively. We characterized prescribed changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targets by autoregulation testing results. Results: A total of 135 patients, median age 31 (interquartile range (IQR) 24, 43) years, 71.9% male, admission Glasgow coma scale (GCS) score 3 (IQR 3, 5.5), and 70.9% with subdural hematoma from severe (GCS 3-8; 133 (98.5%)) and moderate (GCS 9-12; 2 (1.5%)) TBI, underwent 309 attempted testing. All patients were mechanically ventilated and had ICP monitoring; 246 (80%) had brain tissue oxygen monitoring, and 68 (22%) had an external ventricular drain. The median number of autoregulation tests was two (range 1-3) tests/patient, and the median admission to the first test time was two days (IQR 1, 3). Of 55 (17.8%) tests not completed, systemic hypertension (32, 10.4%), intracranial hypertension (10, 3.2%), and bradycardia (3, 0.9%) were transient. Fifty-three (51%) of the first (n=104) autoregulation tests showed impaired/absent cerebral autoregulation. Impaired/absent autoregulation results at the first test were associated with repeat cerebral autoregulation testing (RR 2.25, 95% CI [1.40-3.60], p=0.0007) than intact cerebral autoregulation results. Pre-testing cerebral hemodynamic targets were maintained (n=131; 86.8%) when cerebral autoregulation was impaired (n=151; RR 1.49, 95% CI [1.25-1.77], p<0.0001). However, 15 (9.9%) test results led to higher ICP targets (from 20 mmHg to 25 mmHg), 5 (3.3%) results led to an increase in CPP target (from 60 mmHg to 70 mmHg), and five out of 131 (3.8%) patients underwent decompressive craniectomy and placement of an external ventricular drain. Intact cerebral autoregulation results (n=43/103, 41.7%) were associated with a change in ICP targets from 20 mmHg to 25 mmHg (RR 3.15, 95% CI [1.97-5.03], p<0.0001). Conclusions: Static cerebral autoregulation testing was feasible, safe, and useful in individualizing the care of patients with moderate-severe TBI receiving multimodal neuromonitoring. Testing results guided future testing, cerebral hemodynamic targets, and procedural decisions. Impaired cerebral autoregulation was very common.

Menstrual cycle and oral contraceptives influence cerebrovascular dynamics during hypercapnia.

Women experience fluctuating orthostatic intolerance during the menstrual cycle, suggesting sex hormones may influence cerebral blood flow. Young (aged 18–30) healthy women, either taking oral contraceptives (OC; n = 14) or not taking OC (NOC; n = 12), were administered hypercapnic gas (5%) for 5 min in the low hormone (LH; placebo pill) and high hormone (HH; active pill) menstrual phases. Hemodynamic and cerebrovascular variables were continuously measured. Cerebral blood velocity changes were monitored using transcranial doppler ultrasound of the middle cerebral artery to determine cerebrovascular reactivity. Cerebral autoregulation was assessed using steady‐state analysis (static cerebral autoregulation) and transfer function analysis (dynamic cerebral autoregulation; dCA). In response to hypercapnia, menstrual phase did not influence static cardiovascular or cerebrovascular responses (all p > 0.07); however, OC users had a greater increase of mean middle cerebral artery blood velocity compared to NOC (NOC‐LH 12 ± 6 cm/s vs. NOC‐HH 16 ± 9 cm/s; OC‐LH 18 ± 5 cm/s vs. OC‐HH 17 ± 11 cm/s; p = 0.048). In all women, hypercapnia improved high frequency (HF) and very low frequency (VLF) cerebral autoregulation (decreased nGain; p = 0.002 and <0.001, respectively), whereas low frequency (LF) Phase decreased in NOC‐HH (p = 0.001) and OC‐LH (p = 0.004). Therefore, endogenous sex hormones reduce LF dCA during hypercapnia in the HH menstrual phase. In contrast, pharmaceutical sex hormones (OC use) have no acute influence (HH menstrual phase) yet elicit a chronic attenuation of LF dCA (LH menstrual phase) during hypercapnia.

A novel computational model for cerebral blood flow rate control mechanisms to evaluate physiological cases

In this study, a new numerical model simulating interaction among static cerebral autoregulation, cerebrovascular CO2 and O2 reactivities and systemic peripheral resistance regulation was developed and integrated into a cardiovascular system model including heart chambers, systemic and pulmonary circulations, and cerebral circulation with Circle of Willis. Simulations were performed to evaluate cerebral blood flow in a healthy condition, effect of altered static cerebral autoregulation in heart failure, effect of impaired static cerebral autoregulation in malignant hypertension, effects of arterial CO2 and O2 pressures in hypercapnia, hypocapnia and hypoxemia on cerebral blood flow. Also, sensitivity analysis was performed to assess influence of arterial CO2 and O2 pressure, aortic pressure set point in the cerebral flow autoregulatory function, systemic peripheral resistance, left ventricular active and passive properties on the cerebral blood flow rate. There was a high and positive correlation between cerebral blood flow rate and arterial CO2 pressure whereas left ventricular contractility influenced cerebral blood flow rate slightly. Cerebral blood flow rate in the healthy condition, heart failure, malignant hypertension, hypercapnia, hypocapnia and hypoxemia was 721 mL/min, 606 mL/min, 1313 mL/min, 950 mL/min, 504 mL/min and 972 mL/min, respectively. Simulation results and sensitivity analysis showed that the new numerical model can be used to evaluate cerebral blood flow in various physiological cases.

The effect of propofol-sufentanil intravenous anesthesia on systemic and cerebral circulation, cerebral autoregulation and CO2 reactivity: a case series

Background and objectivesThe aim of our study was to assess systemic and cerebral hemodynamic changes as well as cerebral CO2-reactivity during propofol anesthesia. Methods27 patients undergoing general anesthesia were enrolled. Anesthesia was maintained using the Target-Controlled Infusion (TCI) method according to the Schnider model, effect site propofol concentration of 4 μg.mL-1. Ventilatory settings (respiratory rate and tidal volume) were adjusted to reach and maintain 40, 35, and 30 mmHg EtCO2 for 5 minutes, respectively. At the end of each period, transcranial Doppler and hemodynamic parameters using applanation tonometry were recorded. ResultsSystemic mean arterial pressure significantly decreased during anesthetic induction and remained unchanged during the entire study period. Central aortic and peripherial pulse pressure did not change significantly during anesthetic induction and maintenance, whereas augmentation index as marker of arterial stiffness significantly decreased during the anesthetic induction and remained stable at the time points when target CO2 levels were reached. Both cerebral autoregulation and cerebral CO2-reactivity was maintained during propofol anesthesia. ConclusionsPropofol at clinically administered doses using the Total Intravenous Anesthesia (TIVA/TCI) technique decreases systemic blood pressure, but does not affect static cerebral autoregulation, flow-metabolism coupling and cerebrovascular CO2 reactivity. According to our measurements, propofol may exert its systemic hemodynamic effect through venodilation. Trial registrationThe study was registered at http://www.clinicaltrials.gov, identifier: NCT02203097, registration date: July 29, 2014.

Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease

BackgroundThe cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow.MethodsTranscranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol.ResultsAfter elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [− 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001).ConclusionsThe observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.

The influence of intracranial hypertension on static cerebral autoregulation

ABSTRACT Objectives To analyze the influences of mild and severe intracranial hypertension on cerebral autoregulation (CA). Patients and Methods Duroc piglets were monitored with an intracranial pressure (ICP) catheter. Intracranial hypertension was induced via infusion of 4 or 7 ml of saline solution by a bladder catheter that was inserted into the parietal lobe. The static cerebral autoregulation (sCA) index was evaluated via cerebral blood flow velocities (CBFv). Piglets with ICPs ≤ 25 and > 25 mmHg were considered as group 1 and 2, respectively. Continuous variables were evaluated using the Kolmogorov-Smirnov goodness-of-fit test. The main parameters were collected before and after ICH induction and compared using two-factor mixed-design ANOVAs with the factor of experimental group (mild and severe ICH). Results In group 1 (ICP ≤ 25 mmHg), there were significant differences in sCA (p = .01) and ICP (p = .0002) between the basal and balloon inflation conditions. In group 2 (ICP > 25 mmHg), there were significant differences in CBFv (p = .0072), the sCA index (p = .0001) and ICP (p = .00001) between the basal and balloon inflation conditions. Conclusion We conclude that intracranial hypertension may have a direct effect on sCA

Cerebral autoregulation after aneurysmal subarachnoid haemorrhage. A preliminary study comparing dexmedetomidine to propofol and/or midazolam.

Cerebral autoregulation is often impaired after aneurysmal subarachnoid haemorrhage (aSAH). Dexmedetomidine is being increasingly used, but its effects on cerebral autoregulation in patients with aSAH have not been studied before. Dexmedetomidine could be a useful sedative in patients with aSAH as it enables neurological assessment during the infusion. The aim of this preliminary study was to compare the effects of dexmedetomidine on dynamic and static cerebral autoregulation with propofol and/or midazolam in patients with aSAH. Ten patients were recruited. Dynamic and static cerebral autoregulation were assessed using transcranial Doppler ultrasound during propofol and/or midazolam infusion and then during three increasing doses of dexmedetomidine infusion (0.7, 1.0 and 1.4μg/kg/h). Transient hyperaemic response ratio (THRR) and strength of autoregulation (SA) were calculated to assess dynamic cerebral autoregulation. Static rate of autoregulation (sRoR)% was calculated by using noradrenaline infusion to increase the mean arterial pressure 20mmHg above the baseline. Data from nine patients were analysed. Compared to baseline, we found no statistically significant changes in THRR or sROR%. THRR was (mean±SD) 1.20±0.14, 1.17±0.13 (P=.93), 1.14±0.09 (P=.72) and 1.19±0.18 (P=1.0) and sROR% was 150.89±84.37, 75.22±27.75 (P=.08), 128.25±58.35 (P=.84) and 104.82±36.92 (P=.42) at baseline and during 0.7, 1.0 and 1.4μg/kg/h dexmedetomidine infusion, respectively. Dynamic SA was significantly reduced after 1.0μg/kg/h dexmedetomidine (P=.02). Compared to propofol and/or midazolam, dexmedetomidine did not alter static cerebral autoregulation in aSAH patients, whereas a significant change was observed in dynamic SA. Further and larger studies with dexmedetomidine in aSAH patients are warranted.

Abstract TP479: Early Effect of Human Immunodeficiency Virus on Cerebral Blood Flow and Autoregulation

Introduction: Human immunodeficiency virus (HIV)-infected individuals are at high risk for ischemic stroke. We measured cerebral blood flow (CBF), oxygen extraction fraction (OEF), and autoregulation in HIV infected subjects and controls. Methods: In treatment-naive HIV infected subjects and age-, gender-, and race-matched controls, OEF was measured by using MRI T2*-weighted echo-planar imaging sequences and CBF was measured by MRI pulsed arterial spin labeling (PASL) approach. Static cerebral autoregulation was determined by measuring changes in CBF and OEF, in response to ≈10% reductions in MAP induced by using IV Nicardipine infusion. All images were acquired using a Siemens 3T MR scanner (Treo, Siemens Medical Systems Inc). Cerebral autoregulation was measured globally and regionally in gray matter (GM), white matter (WM) and subcortical GM. Autoregulatory Index (AI) was computed using the equation AI = %CBF change/% MAP change supplemented by CBF associated OEF changes. Nominal p-values are uncorrected for multiple comparisons. Results: Forty-one treatment naive HIV-infected subjects and 47 age-, gender-, race-matched controls participated. HIV-infected subjects had higher CBF in cortical GM compared to the controls (76.8± 12 mL/100 g/min versus 71.6 ± 11 mL/100 g/min; p= 0.04), but not in white matter (30.9± 8 mL/100 g/min versus 30.0 ± 8 mL/100 g/min; p = 0.60) or subcortical GM (62.8± 13 mL/100 g/min versus 61.3 ± 13 mL/100 g/min; p = 0.57). Whole brain (WB), GM, WM, and subcortical GM, OEF were similar between the groups (p &gt; .05). The median AI were similar between cases and controls in WB (0.40 vs 0.18, p=0.86), GM (0.10 vs. 0.16, p=0.87), WM (0.80 vs. 0.87, p=0.31), and subcortical GM (1.65 vs. 1.77, p=0.26). A 12-month follow-up (N=30) in HIV-subjects on antiretroviral therapy did not produce a significant change in CBF or OEF in the WB, GM, WM, or subcortical GM (Paired sample t test p&gt;0.05). Similarly, no changes were noted on the AI (Wilcoxon Match Rank test p&gt;0.05). Conclusions: AI was similar between HIV cases and control and remained so after 12-months of antiretroviral therapy. We found no evidence of a defect in autoregulation to explain the high-risk of ischemic stroke documented in other studies.

Static Cerebral Autoregulation is Not Altered in Symptomatic Concussed Athletes During Acute Central Hypervolemia

Dynamic cerebral autoregulation is impaired in concussed individuals. However, less is known regarding static cerebral autoregulation in symptomatic concussed athletes during a central hypervolemic challenge that increases blood pressure. PURPOSE: We tested the hypothesis that static cerebral autoregulation during a central hypervolemic challenge is impaired in symptomatic concussed college athletes (CA) vs healthy controls (HC). METHODS: Seven CA (age: 19±2 y, 5 females) and ten HC (age: 21±2 y, 6 females) completed one study visit. After 5 min of resting baseline, 20 mmHg of lower body positive pressure (LBPP) was applied for 5 min using an airtight chamber. Beat to beat blood pressure (photoplethysmography) and middle cerebral artery blood velocity (MCAv; transcranial Doppler) were recorded continuously. Static cerebral autoregulation was calculated using Fourier transfer function analysis with 3 min segments at baseline and after mean arterial pressure (MAP) stabilized during LBPP. Cerebral vascular resistance (CVR) was calculated as MAP/MCAv. Pulsatility index (PI) was calculated as the difference of peak systolic MCAv and end diastolic MCAv, divided by mean MCAv. Values are reported as a change from baseline. RESULTS: MAP (CA: 90±6 vs HC: 92±11 mmHg; P=0.32), MCAv (CA: 58.7±19.4 vs HC: 62.6±11.1 cm/s; P=0.30), gain (CA: 0.7±0.2 vs HC: 0.8±0.2 cm/s/mmHg; P=0.17), coherence (CA: 0.5±0.1 vs HC: 0.5±0.1; P=0.21), CVR (CA: 1.7±0.6 vs HC: 1.5±0.3 mmHg/cm/s; P=0.21), and PI (CA: 0.9±0.1 vs HC: 0.9±0.2; P=0.31) were not different at baseline. The change in MAP was not different between CA (12±6 mmHg) and HC (8±6 mmHg; P=0.12). The change in MCAv was greater in CA (CA: 4.8±4.6 vs HC: -4.3±8.7 cm/s; P=0.01). There were no differences in the change from baseline for gain (CA: 0.1±0.2 vs HC: 0.1±0.5 cm/s/mmHg; P=0.49) or coherence (CA: -0.0±0.1 vs HC: -0.0±0.1; P=0.40). The increase in CVR was attenuated in CA (CA: 0.0±0.2 vs HC: 0.3±0.3 mmHg/cm/s; P=0.04). The decrease in PI was greater in CA (CA: -0.1±0.0 vs HC: 0.0±0.1; P=0.02). CONCLUSION: These data indicate that indices of static cerebral autoregulation are not different between CA and HC during an acute increase in MAP. The blunted increase in CVR and greater decrease in PI appears to allow for a rise in MCAv during an acute increase in MAP in CA.

Intracranial Hypertension and Cerebral Autoregulation: A Systematic Review and Meta-Analysis.

To present a systematic review and meta-analysis to establish the relation between cerebral autoregulation (CA) and intracranial hypertension. An electronic search using the term "Cerebral autoregulation and intracranial hypertension" was designed to identify studies that analyzed cerebral blood flow autoregulation in patients undergoing intracranial pressure (ICP) monitoring. The data were used in meta-analyses and sensitivity analyses. A static CA technique was applied in 10 studies (26.3%), a dynamic technique was applied in 25 studies (65.8%), and both techniques were used in 3 studies (7.9%). Static CA studies using the cerebral blood flow technique revealed impaired CA in patients with an ICP ≥20 (standardized mean difference [SMD] 5.44%, 95% confidence interval [CI] 0.25-10.65, P= 0.04); static CA studies with transcranial Doppler revealed a tendency toward impaired CA in patients with ICP ≥20 (SMD -7.83%, 95% CI -17.52 to 1.85, P= 0.11). Moving correlation studies reported impaired CA in patients with ICP ≥20 (SMD 0.06, 95% CI 0.07-0.14, P < 0.00001). A comparison of CA values and mean ICP revealed a correlation between greater ICP and impaired CA (SMD 5.47, 95% CI 1.39-10.1, P= 0.01). Patients with ICP ≥20 had an elevated risk of impaired CA (OR 2.27, 95% CI 1.20-4.31, P= 0.01). A clear tendency toward CA impairment was observed in patients with increased ICP.

Postural effects on cerebral blood flow and autoregulation.

Cerebral autoregulation (CA) is thought to maintain relatively constant cerebral blood flow (CBF) across normal blood pressures. To determine if postural changes alter CA, we measured cerebral blood flow velocity (CBFv) in the middle cerebral arteries, mean arterial blood pressure (MABP), cardiac output (Q), and end‐tidal carbon dioxide (PETCO 2) in 18 healthy individuals (11 female and seven male; 26 ± 9 years) during repeated periods of supine and seated rest. Multiple regression was used to evaluate the influence of PETCO 2, MABP, Q, and hydrostatic pressure on CBFv. Static CA was assessed by evaluating absolute changes in steady‐state CBFv. Dynamic CA was assessed by transfer function analysis of the CBFv response to spontaneous oscillations in MABP. In the seated versus supine posture, MABP (67.2 ± 7.2 vs. 84.2 ± 12.1 mmHg; P < 0.001), CBFv (55.2 ± 9.1 vs. 63.6 ± 10.6 cm/sec; P < 0.001) and PETCO 2 (29.1 ± 2.6 vs. 30.9 ± 2.3 mmHg; P < 0.001) were reduced. Changes in CBFv were not explained by variance in PETCO 2, MABP, Q, or hydrostatic pressure. A reduction in MABP to CBFv transfer function gain while seated (P < 0.01) was explained by changes in the power spectrum of MABP, not CBFv. Our findings suggest that changes in steady‐state cerebral hemodynamics between postures do not appear to have a large functional consequence on the dynamic regulation of CBF.

Compartmental and Data-Based Modeling of Cerebral Hemodynamics: Nonlinear Analysis.

As an extension to our study comparing a putative compartmental and data-based model of linear dynamic cerebral autoregulation (CA) and CO2-vasomotor reactivity (VR), we study the CA-VR process in a nonlinear context. We use the concept of principal dynamic modes (PDM) in order to obtain a compact and more easily interpretable input-output model. This in silico study permits the use of input data with a dynamic range large enough to simulate the classic homeostatic CA and VR curves using a putative structural model of the regulatory control of the cerebral circulation. The PDM model obtained using theoretical and experimental data are compared. It was found that the PDM model was able to reflect accurately both the simulated static CA and VR curves in the associated nonlinear functions (ANFs). Similar to experimental observations, the PDM model essentially separates the pressure-flow relationship into a linear component with fast dynamics and nonlinear components with slow dynamics. In addition, we found good qualitative agreement between the PDMs representing the dynamic theoretical and experimental CO2-flow relationship. Under the modeling assumption and in light of other experimental findings, we hypothesize that PDMs obtained from experimental data correspond with passive fluid dynamical and active regulatory mechanisms. Both hypothesis-based and data-based modeling approaches can be combined to offer some insight into the physiological basis of PDM model obtained from human experimental data. The PDM modeling approach potentially offers a practical way to quantify the status of specific regulatory mechanisms in the CA-VR process.

Myogenic and metabolic feedback in cerebral autoregulation: Putative involvement of arachidonic acid-dependent pathways

The present paper presents a mechanistic model of cerebral autoregulation, in which the dual effects of the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) on vascular smooth muscle mediate the cerebrovascular adjustments to a change in cerebral perfusion pressure (CPP). 20-HETE signalling in vascular smooth muscle mediates myogenic feedback to changes in vessel wall stretch, which may be modulated by metabolic feedback through EETs released from astrocytes and endothelial cells in response to changes in brain tissue oxygen tension. The metabolic feedback pathway is much faster than 20-HETE-dependent myogenic feedback, and the former thus initiates the cerebral autoregulatory response, while myogenic feedback comprises a relatively slower mechanism that functions to set the basal cerebrovascular tone. Therefore, assessments of dynamic cerebral autoregulation, which may provide information on the response time of the cerebrovasculature, may specifically be used to yield information on metabolic feedback mechanisms, while data based on assessments of static cerebral autoregulation represent the integrated functionality of myogenic and metabolic feedback.

Individual variability of cerebral autoregulation, posterior cerebral circulation and white matter hyperintensity.

Cerebral autoregulation (CA) is a key mechanism to protect brain perfusion in the face of changes in arterial blood pressure, but little is known about individual variability of CA and its relationship to the presence of brain white matter hyperintensity (WMH) in older adults, a type of white matter lesion related to cerebral small vessel disease (SVD). This study demonstrated the presence of large individual variability of CA in healthy older adults during vasoactive drug-induced changes in arterial pressure assessed at the internal carotid and vertebral arteries. We also observed, unexpectedly, that it was the 'over-' rather than the 'less-reactive' CA measured at the vertebral artery that was associated with WMH severity. These findings challenge the traditional concept of CA and suggest that the presence of cerebral SVD, manifested as WMH, is associated with posterior brain hypoperfusion during acute increase in arterial pressure. This study measured the individual variability of static cerebral autoregulation (CA) and determined its associations with brain white matter hyperintensity (WMH) in older adults. Twenty-seven healthy older adults (13 females, 66±6years) underwent assessment of CA during steady-state changes in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside (SNP) and phenylephrine. Cerebral blood flow (CBF) was measured using colour-coded duplex ultrasonography at the internal carotid (ICA) and vertebral arteries (VA). CA was quantified by a linear regression slope (CA slope) between percentage changes in cerebrovascular resistance (CVR=MAP/CBF) and MAP relative to baseline values. Periventricular and deep WMH volumes were measured with T2-weighted magnetic resonance imaging. MAP was reduced by -11±7% during SNP, and increased by 21±8% during phenylephrine infusion. CA demonstrated large individual variability with the CA slopes ranging from 0.37 to 2.20 at the ICA and from 0.17 to 3.18 at the VA; no differences in CA were found between the ICA and VA. CA slopes measured at the VA had positive correlations with the total and periventricular WMH volume (r=0.55 and 0.59, P<0.01). Collectively, these findings demonstrated the presence of large individual variability of CA in older adults, and that, when measured in the posterior cerebral circulation, it is the higher rather than lower CA reactivity that is associated with WMH severity.

Assessing cerebrovascular autoregulation from critical closing pressure and resistance area product during upright posture in aging and hypertension.

Static cerebral autoregulation (sCA) is believed to be resistant to aging and hypertensive pathology. However, methods to characterize autoregulation commonly rely on beat-by-beat mean hemodynamic measures and do not consider within-beat pulse wave characteristics that are impacted by arterial stiffening. We examined the role of critical closing pressure (CrCP) and resistance area product (RAP), two measures derived from the pulse wave, across supine lying, sitting, and standing postures in young adults, normotensive older adults, and older adults with controlled and uncontrolled hypertension (N = 80). Traditional measures of sCA, using both intracranial and extracranial methods, indicated similar efficiency across all groups, but within-beat measures suggested different mechanisms of regulation. At rest, RAP was increased in hypertension compared with young adults (P < 0.001), but CrCP was similar. In contrast, the drop in CrCP was the primary regulator of change in cerebrovascular resistance upon adopting an upright posture. Both CrCP and RAP demonstrated group-by-posture interaction effects (P < 0.05), with older hypertensive adults exhibiting a rise in RAP that was absent in other groups. The posture-related swings in CrCP and RAP were related to changes in both the pulsatile and mean components of arterial pressure, independent of age, cardiac output, and carbon dioxide. Group-by-posture differences in pulse pressure were mediated in part by an attenuated heart rate response in older hypertensive adults (P = 0.002). Examination of pulsatile measures in young, elderly, and hypertensive adults identified unique differences in how cerebral blood flow is regulated in upright posture.

Cerebral Hemodynamic Responses to Acupuncture in Migraine Patients: A Systematic Review

We review the literature conjoining acupuncture, migraine, and cerebral hemodynamics. To do so, we searched PubMed in March 2013 for studies investigating cerebral hemodynamics with functional magnetic resonance imaging (fMRI), near-infrared spectroscopy (NIRS), transcranial Doppler (TCD) ultrasound, and other tools in migraineurs, acupuncture recipients, and migraineurs receiving acupuncture. Our search identified 1321 distinct articles – acupuncture (n = 463), migraine (n = 866), and both (n = 8). Only three (n = 3) satisfied our inclusion criteria. Based on these three, we found the following: (1) Acupuncture may positively influence not just dynamic, but also static cerebral autoregulation during the interictal phase, depending on the intervals between sessions of acupuncture as dose units. (2) TCD can detect pretreatment differences between responders and non-responders to acupuncture, which may be predictive of clinical response. (3) “Point-through-point” needling (at angles connecting acupoints) may be clinically superior to standard acupuncture, thus needling angles may affect treatment effectiveness. None of the reviewed articles investigated patient responses during migraine attack. Although the 2009 Cochrane review affirmed acupuncture as effective prophylaxis for migraine, few studies investigated the cerebrovascular aspects – only analyzing arterial blood flow, but not microcirculation. Future research is warranted in monitoring brain tissue oxygenation to investigate acupuncture as both a preventive and abortive treatment for migraine, varying the type and dose interval and analyzing variations in clinical response.

Regulation of Cerebral Blood Flow after Spinal Cord Injury

Significant cardiovascular and autonomic dysfunction occurs after era spinal cord injury (SCI). Two major conditions arising from autonomic dysfunction are orthostatic hypotension and autonomic dysreflexia (i.e., severe acute hypertension). Effective regulation of cerebral blood flow (CBF) is essential to offset these drastic changes in cerebral perfusion pressure. In the context of orthostatic hypotension and autonomic dysreflexia, the purpose of this review is to critically examine the mechanisms underlying effective CBF after an SCI and propose future avenues for research. Although only 16 studies have examined CBF control in those with high-level SCI (above the sixth thoracic spinal segment), it appears that CBF regulation is markedly altered in this population. Cerebrovascular function comprises three major mechanisms: (1) cerebral autoregulation, (i.e., ΔCBF/Δ blood pressure); (2) cerebrovascular reactivity to changes in PaCO2 (i.e. ΔCBF/arterial gas concentration); and (3) neurovascular coupling (i.e., ΔCBF/Δ metabolic demand). While static cerebral autoregulation appears to be well maintained in high-level SCI, dynamic cerebral autoregulation, cerebrovascular reactivity, and neurovascular coupling appear to be markedly altered. Several adverse complications after high-level SCI may mediate the changes in CBF regulation including: systemic endothelial dysfunction, sleep apnea, dyslipidemia, decentralization of sympathetic control, and dominant parasympathetic activity. Future studies are needed to describe whether altered CBF responses after SCI aid or impede orthostatic tolerance. Further, simultaneous evaluation of extracranial and intracranial CBF, combined with modern structural and functional imaging, would allow for a more comprehensive evaluation of CBF regulatory processes. We are only beginning to understand the functional effects of dysfunctional CBF regulation on brain function on persons with SCI, which are likely to include increased risk of transient ischemic attacks, stroke, and cognitive dysfunction.

Cerebrovascular and blood pressure control at rest and during exercise in Spinal Cord Injury

Spinal Cord Injury (SCI) results in significant cardiovascular autonomic dysfunction dependent on the level and completeness of lesion. Impaired cardiovascular control in SCI is associated with loss of sympathetic neural control of the heart and vasculature and can result in precipitous variations in blood pressure, such as Orthostatic Hypotension and Autonomic Dysreflexia. Individuals with SCI are at higher risk of cerebrovascular disease, such as stroke and transient ischemic attacks. Cerebral blood flow (CBF) is thought to remain relatively constant within a range of blood pressures, known as cerebral autoregulation (CA) which comprises two components; static and dynamic CA.