Cerebrovascular Resistance Research Articles

The Influence of Carbon Dioxide on Cerebral Autoregulation During Sevoflurane-based Anesthesia in Patients With Type 2 Diabetes.

Cerebral autoregulation (CA) continuously adjusts cerebrovascular resistance to maintain cerebral blood flow (CBF) constant despite changes in blood pressure. Also, CBF is proportional to changes in arterial carbon dioxide (CO 2 ) (cerebrovascular CO 2 reactivity). Hypercapnia elicits cerebral vasodilation that attenuates CA efficacy, while hypocapnia produces cerebral vasoconstriction that enhances CA efficacy. In this study, we quantified the influence of sevoflurane anesthesia on CO 2 reactivity and the CA-CO 2 relationship. We studied patients with type 2 diabetes mellitus (DM), prone to cerebrovascular disease, and compared them to control subjects. In 33 patients (19 DM, 14 control), end-tidal CO 2 , blood pressure, and CBF velocity were monitored awake and during sevoflurane-based anesthesia. CA, calculated with transfer function analysis assessing phase lead (degrees) between low-frequency oscillations in CBF velocity and mean arterial blood pressure, was quantified during hypocapnia, normocapnia, and hypercapnia. In both control and DM patients, awake CO 2 reactivity was smaller (2.8%/mm Hg CO 2 ) than during sevoflurane anesthesia (3.9%/mm Hg; P <0.005). Hyperventilation increased CA efficacy more (3 deg./mm Hg CO 2 ) in controls than in DM patients (1.8 deg./mm Hg CO 2 ; P <0.001) in both awake and sevoflurane-anesthetized states. The CA-CO 2 relationship is impaired in awake patients with type 2 DM. Sevoflurane-based anesthesia does not further impair this relationship. In patients with DM, hypocapnia induces cerebral vasoconstriction, but CA efficacy does not improve as observed in healthy subjects.

Renal Dysfunction Is Associated with Middle Cerebral Artery Pulsatility Index and Total Burden of Cerebral Small Vessel Disease

Background and Purpose: Renal dysfunction is known to affect vasculature and lead to systemic arterial stiffness. It also independently increases the risk of cerebral small vessel disease (cSVD) and stroke. We aimed to examine the effect of renal dysfunction on cerebral hemodynamics and the burden of cSVD. Methods: Of the 412 patients admitted to Seoul National University Hospital, between May 2015 and 2019, with lacunar infarction and no major intracranial arterial stenosis observed on magnetic resonance angiography, we included 283 patients who had undergone a transcranial Doppler (TCD) ultrasound after 72 h of stroke onset. The patients were divided into renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m² at admission) and control (eGFR ≥60 mL/min/1.73 m²) groups. We investigated the correlations between renal function, the pulsatility index (PI), and the total MRI burden of cSVD. Furthermore, multivariate analysis was performed to assess the association between renal dysfunction and the PI of the middle cerebral artery (MCA) measured through TCD ultrasound. Results: Among the total patients, 74 (26.1%) had renal dysfunction (eGFR <60 mL/min/1.73 m² at admission). Patients with renal dysfunction were significantly older, showed higher pulse pressure, and had a higher prevalence of hypertension, diabetes mellitus, and coronary artery disease. Renal dysfunction was significantly associated with higher distal cerebrovascular flow resistance (median PI 1.12, interquartile range [IQR]: 0.85–1.57 vs. controls 0.84, IQR: 0.54–1.22; p < 0.001). Also, patients with renal dysfunction had a significantly higher total MRI burden of cSVD (median cSVD score 2, IQR: 1–3 vs. controls median score 1, IQR: 0–2; p < 0.001). There was an inverse proportional relationship between the PI and eGFR. Finally, multivariate analysis showed renal dysfunction (adjusted odds ratio: 4.516, 95% confidence interval: 1.051–20.292) and older age (adjusted odds ratio: 1.076, 95% confidence interval: 1.038–1.114) as independent predictors of a high PI. Conclusions: Renal dysfunction is independently associated with a high PI of MCA. Renal dysfunction leads to systemic arterial stiffness including stiffness in cerebral arteries, thus increasing the burden of cSVD. Therefore, noninvasive screening for high PI by TCD in kidney failure patients might be helpful.

Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study

Accumulating evidence suggests vascular dysregulation in preclinical Alzheimer’s disease. In this study, cerebral hemodynamics and their coupling with cognition in middle-aged apolipoprotein ε4 carriers (APOEε4+) were investigated. Longitudinal 3 T T1-weighted and arterial spin labelling MRI data from 158 participants (40–59 years old) in the PREVENT-Dementia study were analysed (125 two-year follow-up). Cognition was evaluated using the COGNITO battery. Cerebral blood flow (CBF) and cerebrovascular resistance index (CVRi) were quantified for the flow territories of the anterior, middle and posterior cerebral arteries. CBF was corrected for underlying atrophy and individual hematocrit. Hemodynamic measures were the dependent variables in linear regression models, with age, sex, years of education and APOEε4 carriership as predictors. Further analyses were conducted with cognitive outcomes as dependent variables, using the same model as before with additional APOEε4 × hemodynamics interactions. At baseline, APOEε4+ showed increased CBF and decreased CVRi compared to non-carriers in the anterior and middle cerebral arteries, suggestive of potential vasodilation. Hemodynamic changes were similar between groups. Interaction analysis revealed positive associations between CBF changes and performance changes in delayed recall (for APOEε4 non-carriers) and verbal fluency (for APOEε4 carriers) cognitive tests. These observations are consistent with neurovascular dysregulation in middle-aged APOEε4+.

Percutaneous Trigeminal Nerve Stimulation Induces Cerebral Vasodilation in a Dose-Dependent Manner.

The trigeminal nerve directly innervates key vascular structures both centrally and peripherally. Centrally, it is known to innervate the brainstem and cavernous sinus, whereas peripherally the trigemino-cerebrovascular network innervates the majority of the cerebral vasculature. Upon stimulation, it permits direct modulation of cerebral blood flow (CBF), making the trigeminal nerve a promising target for the management of cerebral vasospasm. However, trigeminally mediated cerebral vasodilation has not been applied to the treatment of vasospasm. To determine the effect of percutaneous electrical stimulation of the infraorbital branch of the trigeminal nerve (pTNS) on the cerebral vasculature. In order to determine the stimulus-response function of pTNS on cerebral vasodilation, CBF, arterial blood pressure, cerebrovascular resistance, intracranial pressure, cerebral perfusion pressure, cerebrospinal fluid calcitonin gene-related peptide (CGRP) concentrations, and the diameter of cerebral vessels were measured in healthy and subarachnoid hemorrhage (SAH) rats. The present study demonstrates, for the first time, that pTNS increases brain CGRP concentrations in a dose-dependent manner, thereby producing controllable cerebral vasodilation. This vasodilatory response appears to be independent of the pressor response induced by pTNS, as it is maintained even after transection of the spinal cord at the C5-C6 level and shown to be confined to the infraorbital nerve by administration of lidocaine or destroying it. Furthermore, such pTNS-induced vasodilatory response of cerebral vessels is retained after SAH-induced vasospasm. Our study demonstrates that pTNS is a promising vasodilator and increases CBF, cerebral perfusion, and CGRP concentration both in normal and vasoconstrictive conditions.

Effects of cardiorespiratory fitness and exercise training on cerebrovascular blood flow and reactivity: a systematic review with meta-analyses.

We address two aims: Aim 1 (Fitness Review) compares the effect of higher cardiorespiratory fitness (CRF) (e.g., endurance athletes) with lower CRF (e.g., sedentary adults) on cerebrovascular outcomes, including middle cerebral artery velocity (MCAv), cerebrovascular reactivity and resistance, and global cerebral blood flow, as assessed by transcranial Doppler (TCD) or magnetic resonance imaging (MRI). Aim 2 (Exercise Training Review) determines the effect of exercise training on cerebrovascular outcomes. Systematic review of studies with meta-analyses where appropriate. Certainty of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty studies (18 using TCD) met the eligibility criteria for Aim 1, and 14 studies (8 by TCD) were included for Aim 2. There was a significant effect of higher CRF compared with lower CRF on cerebrovascular resistance (effect size = -0.54, 95% confidence interval = -0.91 to -0.16) and cerebrovascular reactivity (0.98, 0.41-1.55). Studies including males only demonstrated a greater effect of higher CRF on cerebrovascular resistance than mixed or female studies (male only: -0.69, -1.06 to -0.32; mixed and female studies: 0.10, -0.28 to 0.49). Exercise training did not increase MCAv (0.05, -0.21 to 0.31) but showed a small nonsignificant improvement in cerebrovascular reactivity (0.60, -0.08 to 1.28; P = 0.09). Exercise training showed heterogeneous effects on regional but little effect on global cerebral blood flow as measured by MRI. High CRF positively effects cerebrovascular function, including decreased cerebrovascular resistance and increased cerebrovascular reactivity; however, global cerebral blood flow and MCAv are primarily unchanged following an exercise intervention in healthy and clinical populations.NEW & NOTEWORTHY Higher cardiorespiratory fitness is associated with lower cerebrovascular resistance and elevated cerebrovascular reactivity at rest. Only adults with a true-high fitness based on normative data exhibited elevated middle cerebral artery velocity. The positive effect of higher compared with lower cardiorespiratory fitness on resting cerebrovascular resistance was more evident in male-only studies when compared with mixed or female-only studies. A period of exercise training resulted in negligible changes in middle cerebral artery velocity and global cerebral blood flow, with potential for improvements in cerebrovascular reactivity.

Cerebrovascular tone and resistance measures differ between healthy control and patients with acute intracerebral haemorrhage: exploratory analyses from the BREATHE-ICH study

Objective. Cerebral autoregulation impairment in acute neurovascular disease is well described. The recent BREATHE-ICH study demonstrated improvements in dynamic cerebral autoregulation, by hypocapnia generated by hyperventilation, in the acute period following intracranial haemorrhage (ICH). This exploratory analysis of the BREATHE-ICH dataset aims to examine the differences in hypocapnic responses between healthy controls and patients with ICH, and determine whether haemodynamic indices differ between baseline and hypocapnic states. Approach. Acute ICH patients were recruited within 48 h of onset and healthy volunteers were recruited from a university setting. Transcranial Doppler measurements of the middle cerebral artery were obtained at baseline and then a hyperventilation intervention was used to induce hypocapnia. Patients with ICH were then followed up at 10–14 D post-event for repeated measurements. Main results. Data from 43 healthy controls and 12 patients with acute ICH met the criteria for statistical analysis. In both normocapnic and hypocapnic conditions, significantly higher critical closing pressure and resistance area product were observed in patients with ICH. Furthermore, critical closing pressure changes were observed to be sustained at 10–14 D follow up. During both the normocapnic and hypocapnic states, reduced autoregulation index was observed bilaterally in patients with ICH, compared to healthy controls. Significance. Whilst this exploratory analysis was limited by a small, non-age matched sample, significant differences between ICH patients and healthy controls were observed in factors associated with cerebrovascular tone and resistance. These differences suggest underlying cerebral autoregulation changes in ICH, which may play a pivotal role in the morbidity and mortality associated with ICH.

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy.

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation—the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)—all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.

Fetal cerebrovascular response to maternal hyperoxygenation in congenital heart disease: effect of cardiac physiology.

Fetal cerebrovascular resistance is influenced by several factors in the setting of intact autoregulation to allow for normal cerebral blood flow and oxygenation. Maternal hyperoxygenation (MH) allows for acute alterations in fetal physiology and can be a tool to test cerebrovascular reactivity in late-gestation fetuses. In this study, we utilized MH to evaluate cerebrovascular reactivity in fetuses with specific congenital heart disease (CHD). This was a cross-sectional study of fetuses with complex CHD compared to controls without CHD. CHD cases were grouped according to physiology into: left-sided obstructive lesion (LSOL), right-sided obstructive lesion (RSOL) or dextro-transposition of the great arteries (d-TGA). Subjects underwent MH testing during the third-trimester fetal echocardiogram. The pulsatility index (PI) was calculated for the fetal middle cerebral artery (MCA), umbilical artery (UA) and branch pulmonary artery (PA). The change in PI from baseline to during MH was compared between each CHD group and controls. Sixty pregnant women were enrolled (CHD, n = 43; control, n = 17). In the CHD group, there were 27 fetuses with LSOL, seven with RSOL and nine with d-TGA. Mean gestational age was 33.9 (95% CI, 33.6-34.2) weeks. At baseline, MCA-PI Z-score was lowest in the LSOL group (-1.8 (95% CI, -2.4 to -1.2)) compared with the control group (-0.8 (95% CI, -1.3 to -0.3)) (P = 0.01). In response to MH, MCA-PI Z-score increased significantly in the control and d-TGA groups but did not change significantly in the LSOL and RSOL groups. The change in MCA-PI Z-score was significantly higher in the control group than in the LSOL group (0.9 (95% CI, 0.42-1.4) vs 0.12 (95% CI, -0.21 to 0.45); P = 0.03). This difference was more pronounced in the LSOL subgroup with retrograde aortic arch flow. Branch PA-PI decreased significantly in response to MH in all groups, with no difference in the change from baseline to MH between the groups, while UA-PI was unchanged during MH compared with at baseline. The fetal cerebrovascular response to MH varies based on the underlying CHD diagnosis, suggesting that cardiovascular physiology may influence the autoregulatory capacity of the fetal brain. Further studies are needed to determine the clinical implications of these findings on long-term neurodevelopment in these at-risk children. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

CAROTID VASCULAR RESISTANCE ASSOCIATED WITH COGNITIVE FUNCTION AMONG MIDDLE-AGE ADULTS

Objective: Carotid flow velocity and peripheral blood pressure were independently associated with cognitive function among the elderly population, but unknown among middle-aged adults. We aimed to investigate the association between carotid hemodynamics and cognitive performance among the middle-age population. Design and method: A total of 490 middle-age adults (between 30 and 60 years) participated in the ongoing survey (2017–2020) of the Cardiovascular Disease Risk Factors two-Township study and received the Montreal Cognitive Assessment (MOCA) to evaluate the global cognitive function. Carotid-formal pulse wave velocity (cf-PWV) was measured using carotid and femoral arterial tonometry. Carotid vascular resistance was calculated by mean carotid pressure divided into mean carotid volume flow. Results: MOCA levels were similar between men and women (27.1 vs. 27.2, p = 0.6036). Age(r = -0.22, P &lt; 0.001), and education(r = 0.39, p &lt; 0.001) were associated with MOCA. Controlled for age, gender and education, peak systolic velocity (r = 0.077 @left; r = 0.012@Right, all p &gt; 0.05), end diastolic velocity (r = 0.029, r = -0.062, all p &gt; 0.05), mean flow (r = 0.060; r = -0.038, all p &gt; 0.05), carotid resistive index (r = 0.020, r = 0.05, all p &gt; 0.05), carotid pulsatility(r = 0.015; r = 0.058; p &gt; 0.05), diameter(r = 0.060; r = -0.008, all p &gt; 0.05) at both sides were not associated with MOCA. Only carotid vascular resistance (CVR) at left side was associated with MOCA (r = -0.158, p = 0.0010), but not at right carotid artery (r = -0.030, p = 0.5369). CVR@Left (standard beta = -0.144; p = 0.0022) remains associated with MOCA in the multivariable with further controlling glucose, low density lipoprotein and carotid-formal pulse wave velocity. Those with top, 2nd and 3th quartile of CVR@left had 2.4-fold [Odds Ratio = 2.40; 95% confidence intervals = 1.14–5.04], 1.95-fold(1.95;0.93–4.07) and 0.99-fold (0.99;0.45–2.17) risk for poor cognitive performance (MOCA &lt; 26), compared to those with lowest quartile of CVR@left in the multivariable model. Conclusions: Carotid vascular resistance is a marker of cerebrovascular resistance and associated with cognitive performance in middle-aged adults.

The Use of Near-Infrared Spectroscopy and/or Transcranial Doppler as Non-Invasive Markers of Cerebral Perfusion in Adult Sepsis Patients With Delirium: A Systematic Review.

Background:Several studies have previously reported the presence of altered cerebral perfusion during sepsis. However, the role of non-invasive neuromonitoring, and the impact of altered cerebral perfusion, in sepsis patients with delirium remains unclear.Methods:We performed a systematic review of studies that used near-infrared spectroscopy (NIRS) and/or transcranial Doppler (TCD) to assess adults (≥18 years) with sepsis and delirium. From study inception to July 28, 2020, we searched the following databases: Ovid MedLine, Embase, Cochrane Library, and Web of Science.Results:Of 1546 articles identified, 10 met our inclusion criteria. Although NIRS-derived regional cerebral oxygenation was consistently lower, this difference was only statistically significant in one study. TCD-derived cerebral blood flow velocity was inconsistent across studies. Importantly, both impaired cerebral autoregulation during sepsis and increased cerebrovascular resistance were associated with delirium during sepsis. However, the heterogeneity in NIRS and TCD devices, duration of recording (from 10 seconds to 72 hours), and delirium assessment methods (e.g., electronic medical records, confusion assessment method for the intensive care unit), precluded meta-analysis.Conclusion:The available literature demonstrates that cerebral perfusion disturbances may be associated with delirium in sepsis. However, future investigations will require consistent definitions of delirium, delirium assessment training, harmonized NIRS and TCD assessments (e.g., consistent measurement site and length of recording), as well as the quantification of secondary and tertiary variables (i.e., Cox, Mxa, MAPOPT), in order to fully assess the relationship between cerebral perfusion and delirium in patients with sepsis.

Carotid Arterial Stiffness and Cerebral Blood Flow in Amnestic Mild Cognitive Impairment.

Central arterial stiffness is an emerging risk factor of age-related cognitive impairment and Alzheimer's disease (AD). However, the underlying pathophysiological mechanisms remain unclear. We tested the hypothesis that carotid arterial stiffness is associated with reduced cerebral blood flow (CBF) and increased cerebrovascular resistance (CVR) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD. Fifty-four patients with amnestic MCI and 24 cognitively normal subjects (CN) of similar age and sex to MCI patients underwent measurements of CBF and carotid β-stiffness index using ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass (assessed with MRI) to obtain normalized CBF (nCBF). Relative to CN subjects, MCI patients showed lower nCBF (53.3 ± 3.2 vs 50.4±3.4 mL/100 g/min, P < 0.001) and higher CVR (0.143 ± 0.019 vs 0.156 ± 0.023 mmHg/mL/min, P < 0.015). Multiple linear regression analysis showed that nCBF was negatively associated with carotid β-stiffness index (B = -0.822, P < 0.001); CVR was positively associated with carotid systolic pressure (B = 0.001, P < 0.001) after adjustment for age, sex, body mass index, and MCI status. These findings suggest that carotid artery stiffening may contribute at least in part to the reduced nCBF and increased CVR in patients with MCI associated with augmented carotid arterial pulsatility.

Cerebral autoregulation in hypertensive patients: A review

Cerebral Autoregulation (AR) consists of a complex mechanism characterized by the ability of the brain microcirculation to contract and dilate in response to variations in Blood Pressure (BP), aiming at maintaining a constant Cerebral Blood Flow (CBF). Vascular changes induced by Systemic Arterial Hypertension (SAH), such as thickening of the smooth muscle layer and intimal proliferation, result in reduced luminal diameter and increased cerebrovascular resistance (CVR). Here, the mechanisms of AR and the repercussions of these histological changes on the microcirculatory capacity to maintain constant CBF in these patients will be reviewed. The material for this review was taken mostly from electronic journals. To collect publications, PubMed e Cochrane database of systematic reviews were used.

Mean arterial pressure during cerebral perfusion MRI: An arterial spin‐labeling study in younger and older adults

AbstractBackgroundHigh blood pressure (BP) and low cerebral blood flow (CBF) have been independently related to Alzheimer’s disease (AD) pathophysiology. Increased cerebrovascular resistance index (CVRi), the ratio of mean arterial pressure (MAP) to CBF, has also been linked to AD risk in older adults. Autoregulatory mechanisms maintain steady perfusion across a range of MAP values through changes in cerebrovascular resistance in healthy individuals. Age‐dependent cerebrovascular stiffening can disrupt cerebrovascular resistance, leaving the brain vulnerable to hypoperfusion with increased MAP. No studies have evaluated MAP during perfusion MRI to further evaluate whether high BP may be related to lower CBF, and whether this relationship is age‐dependent. We studied MAP during perfusion MRI in a sample of younger and older adults using an MRI‐compatible device to continuously monitor MAP.MethodCommunity‐dwelling older adults (n=21; age 56‐87) free of dementia or stroke, and healthy younger adults (n=16; age 18‐34) underwent resting pseudo‐continuous arterial spin‐labelling (pCASL)‐MRI to quantify CBF during simultaneous in‐scanner, continuous MAP monitoring. Average MAP and CBF were calculated over the 5 minute scan. Multiple linear regression examined the relationship between MAP and CBF for younger and older adults, controlling for age and sex.ResultOlder adults with higher MAP during perfusion MRI exhibited significantly lower CBF levels (R2 = .49, β = ‐.23, p = .02). MAP showed no significant relationship with CBF in younger adults.ConclusionThis is the first study to evaluate MAP during perfusion MRI. Findings indicate that higher MAP is correlated with lower CBF in real time in older adults only. We hypothesize that higher MAP may cause decreased CBF through chronic increases in cerebrovascular resistance. Our approach utilizes pCASL‐MRI, capturing CBF to capillaries and smaller arterioles that are susceptible to age‐related microvascular injury. It remains unclear whether the relationship between MAP and microvascular perfusion plays a role in the increased dementia risk associated with high CVRi, but increased CVRi and decreased CBF are associated with dementia. Future work will explore the role of BP during perfusion MRI and whether it may contribute to diagnosis, prognosis or treatment decision‐making to help prevent dementia.

LDL cholesterol may have protective properties for brain health in older age: Do we need to re‐think current guidelines?

AbstractBackgroundElevated low‐density lipoprotein (LDL) cholesterol is a major contributor to cardiovascular diseases (CVD), which are associated with accelerated cognitive decline. However, recent studies suggest LDL cholesterol to be protective against cognitive decline in the very elderly (&gt;85 years). We investigated associations between serum LDL cholesterol, cerebrovascular function and cognition in community‐dwelling adults aged 50‐80 years, testing for differences between mid‐life (50‐64 years) and older age (65‐80 years).MethodOur cross‐sectional analysis used baseline assessments from 236 older adults (78% female, age: 65±0.5 years, BMI: 28.2±0.3 kg/m2, LDL: 3.7±0.1 mmol/L) participating in two intervention trials investigating effects of vasoactive nutrients on cognition, cerebrovascular function and cardiometabolic biomarkers. None were taking statin medication. Assessments included a battery of 10 neuropsychological tests, transcranial Doppler ultrasound to measure cerebral blood flow velocity (BFV) and cerebrovascular resistance index (CVRi), clinic blood pressure and a fasted venous blood sample to measure serum cholesterol.ResultLDL cholesterol correlated with Framingham CVD risk in mid‐life (R=0.360, P&lt;0.001), but not in older adults (R=‐0.124, P=0.174). In adults aged &gt;65 years (n=122), higher LDL cholesterol correlated with higher mean BFV (R=0.255, P=0.009), lower CVRi (R=‐0.266, P=0.006) and higher overall cognitive performance (R=0.228, P=0.011). The latter two were inversely correlated (R=‐0.154, P=0.024, age adjusted).ConclusionLDL cholesterol appears to have a positive association with cerebrovascular and cognitive functions in advanced age; hence, pharmacologically reducing LDL cholesterol to &lt;2mmol/L as currently recommended might not be beneficial for this age group. Further research is warranted to establish optimal LDL cholesterol levels in the elderly.

Sex differences in the autonomic and cerebrovascular responses to upright tilt.

Sex differences in the regulation of autonomic and cerebrovascular responses to orthostatic stress remain unclear. The objectives of this study were to concurrently investigate autonomic control and cerebrovascular resistance indices, including critical closing pressure (CrCP) and resistance area product (RAP), during upright tilt in men and women. In 13 women and 14 men (18-29years), ECG, non-invasive blood pressure, middle cerebral artery blood velocity, and end-tidal CO2 (ETCO2) were continuously measured during supine rest and 70° tilt. Heart rate variability (HRV), cardiovagal baroreflex sensitivity (cBRS), and transfer function parameters of dynamic cerebral autoregulation were calculated. Compared to supine, upright tilt increased the low frequency-to-high frequency ratio of HRV in men only (P=0.044), and decreased cBRS more in women (P=0.001). Cerebrovascular resistance index (CVRi) increased during tilt only in men (sex-by-time interaction: P=0.004). RAP was lower in women throughout tilt (main effect of sex: P=0.022). CrCP decreased during tilt in both sexes (main effect of time: P<0.001). Normalizing to ETCO2 did not alter the effect of tilt on cerebrovascular resistance. Men displayed a greater increase of sympathetic indices and CVRi during tilt while women had greater parasympathetic withdrawal. We hypothesize that increased sympathetic activity in men may drive sex differences in the cerebrovascular response to upright posture.

The critical closing pressure contribution to dynamic cerebral autoregulation in humans: influence of arterial partial pressure of CO2.

Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia. Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV; transcranial Doppler ultrasound), end-tidal CO2 (capnography) and heart rate (ECG) were performed for 5min at rest (normocapnia) and during hypercapnia induced by breathing 5% CO2 in air. CrCP and the resistance-area product (RAP) were obtained for each cardiac cycle and their dynamic response to a step change in MAP was calculated by means of transfer function analysis. The recovery of the CBFV response, following a step change in MAP, was mainly due to the contribution of RAP during both breathing conditions. However, CrCP made a highly significant contribution during normocapnia (P<0.0001) and was the sole determinant of changes in the CBFV response, resulting from hypercapnia, which led to a reduction in the autoregulation index from 5.70±1.58 (normocapnia) to 4.14±2.05 (hypercapnia; P<0.0001). In conclusion, CrCP makes a very significant contribution to the dynamic CBFV response to changes in MAP and plays a major role in explaining the deterioration of dynamic CA induced by hypercapnia. Further studies are needed to assess the relevance of CrCP contribution in physiological and clinical studies.

Evaluation of cerebral autoregulation performance in patients with arterial hypertension on drug treatment.

Cerebral autoregulation (AR) keeps cerebral blood flow constant despite fluctuations in systemic arterial pressure. The final common AR pathway is made up of vasomotor adjustments of cerebrovascular resistance mediated by arterioles. Structural and functional changes in the arteriolar wall arise with age and systemic arterial hypertension. This study evaluated whether AR is impaired in hypertensive patients and whether this impairment differs with disease control. Three groups of patients were prospectively compared: hypertensive patients under treatment with systolic blood pressure (SBP) <140 and diastolic blood pressure (DBP) <90mmHg (n=54), hypertensive patients under treatment with SBP>140 or DBP>90mmHg (n=31), and normotensive volunteers (n=30). Simultaneous measurements of cerebral blood flow velocity (CBFV) and BP were obtained by digital plethysmography and transcranial Doppler, and the AR index (ARI) was defined according to the step response to spontaneous fluctuations in BP. Compared to the uncontrolled hypertension, the normotensive individuals were younger (age 43.42±11.14, P<.05) and had a lower resistance-area product (1.17±0.24, P<.05), although age and greater arteriolar stiffness did not affect the CBFV mean of hypertensive patients, whether controlled or uncontrolled (62.85×58.49×58.30cm/s, P=.29), most likely because their ARIs were not compromised (5.54×5.91×5.88, P=.6). Hypertensive patients under treatment, regardless of their BP control, have intact AR capacity.

The Effects of Hypocapnia on Brain Tissue Pulsations.

Hypocapnia is known to affect patients with acute stroke and plays a key role in governing cerebral autoregulation. However, the impact of hypocapnia on brain tissue pulsations (BTPs) is relatively unexplored. As BTPs are hypothesised to result from cerebrovascular resistance to the inflow of pulsatile arterial blood, it has also been hypothesised that cerebral autoregulation changes mediated by hypocapnia will alter BTP amplitude. This healthy volunteer study reports measurements of BTPs obtained using transcranial tissue Doppler (TCTD). Thirty participants underwent hyperventilation to induce mild hypocapnia. BTP amplitude, EtCO2, blood pressure, and heart rate were then analysed to explore the impact of hypocapnia on BTP amplitude. Significant changes in BTP amplitude were noted during recovery from hypocapnia, but not during the hyperventilation manoeuvre itself. However, a significant increase in heart rate and pulse pressure and decrease in mean arterial pressure were also observed to accompany hypocapnia, which may have confounded our findings. Whilst further investigation is required, the results of this study provide a starting point for better understanding of the effects of carbon dioxide levels on BTPs. Further research in this area is needed to identify the major physiological drivers of BTPs and quantify their interactions with other aspects of cerebral haemodynamics.

The Short-Term Effects of Remote Ischaemic Conditioning on Cerebral Haemodynamics and Cerebral Autoregulation in Healthy Individuals

Remote Ischaemic conditioning (RIC), where brief cycles of ischaemia and reperfusion are applied to the limbs, may improve neurological outcome in acute stroke and reduce recurrent stroke. The short-term effect of RIC on the regulation of cerebral blood flow (CBF), one possible mechanism for these benefits, was investigated. Healthy participants underwent 5-minute recordings in beat-to-beat blood pressure (BP), electrocardiogram (heart rate, HR), end-tidal CO2 and cerebral blood flow velocity (CBFV) with transcranial Doppler insonation of the middle cerebral arteries, before and after four cycles of RIC using 5-min inflation of bilateral thigh cuffs followed by 5-min deflation. Mean values were calculated together with estimates for cerebrovascular resistance, transfer function analysis (TFA) and autoregulation index (ARI). Twenty-five individuals (10 male), aged 28 ± 11 years, had increases in mean and diastolic BP after RIC (113 ± 13 vs. 116 ± 13, p = 0.046; 74 ± 8 vs. 76 ± 9 mmHg, p = 0.03; respectively). Systolic and mean CBFV decreased after RIC (94.5 ± 17.7 vs. 90.0 ± 15.5, p = 0.001; 63.9 ± 11.1 vs. 62.2 ± 10.5 cm s–1, p = 0.02; respectively), as well as pulsatility index (0.77 ± 0.11 vs 0.73 ± 0.11, p = 0.001). No changes occurred in ARI. TFA showed changes in very low frequency range with significantly increased power oscillations (BP and CBFV) and reduction in phase shift (1.04 ± 0.35 vs. 0.76 ± 0.34 radians, p < 0.01). RIC using bilateral thigh cuffs achieved short-term changes to the cerebrovascular and cardiovascular systems. Further evidence is required to establish the effects in a stroke population.

Transcranial Doppler Can Predict Development and Outcome of Sepsis-Associated Encephalopathy in Pediatrics With Severe Sepsis or Septic Shock.

Background and Aim: Sepsis is a common cause of pediatric intensive care unit (ICU) admission. Sepsis-associated encephalopathy (SAE) may occur owing to brain dysfunction in those patients and may be related to impaired cerebral microcirculation. Transcranial Doppler (TCD) can be used to detect this impairment. In this study, we aimed to assess the role of TCD in prediction of SAE and mortality in patients with severe sepsis or septic shock admitted to PICU.Patients and Methods: This prospective study included 75 children admitted to PICU owing to severe sepsis or septic shock. Upon admission, all patients were subjected to careful history taking, thorough clinical examination, and standard laboratory workup. Severity of clinical illness was assessed using the Pediatric Risk of Mortality (PRISM) III score. TCD was performed on the first day of admission after the normalization of systolic blood pressure with or without vasopressors. The primary study outcome was differences in the measurement of TCD in SAE, and the secondary outcome was discharge from ICU or mortality.Results: The study comprised 45 children with SAE and 30 age- and sex-matched children without SAE. In this study, SAE patients had significantly higher pulsatility index [PI; median interquartile range (IQR): 1.15 (0.98–1.48) vs. 1.0 (0.95–1.06), p = 0.002] and resistive index [RI; median (IQR): 0.68 (0.61–0.77) vs. 0.62 (0.59–0.64), p = 0.001] than had non-SAE patients. PI and RI showed good performance as predictors of subsequent SAE development [area under the curve (AUC): 0.72 and 0.73, respectively]. Non-survivors in SAE patients had significantly higher PRISM III. Receiver operating characteristic (ROC) curve analysis showed good performance of PI and RI as predictors of mortality at the end of follow-up.Conclusions: In children with SAE, cerebrovascular resistance is high and is associated with increased mortality.