Transfer Function Gain Research Articles

Preeclampsia postpartum: Impairment of cerebral autoregulation and reversible cerebral hyperperfusion.

Preeclampsia is a pregnancy-related hypertensive disorder with endothelial dysfunction. Impaired cerebral autoregulation may lead to symptomatic cerebral hyperperfusion, which sometimes manifests not until after delivery. This study investigated, whether cerebral autoregulation was altered after delivery in healthy and preeclamptic women, and whether this associated with cerebral hyperperfusion. In a prospective study, 35 preeclamptic and 35 healthy women were examined with transcranial Doppler within 10 days postpartum and 6 months later. Continuous arterial blood pressure and cerebral blood flow velocities (CBFV) in the middle (MCA) and posterior cerebral arteries (PCA) were recorded at rest. Dynamic cerebral autoregulation was assessed upon regular breathing at 0.1 Hz via transfer function phase and gain between arterial blood pressure and CBFV oscillations. In preeclamptic women, phase was reduced after delivery in both, MCA and PCA. During the postpartum period, CBFV of the MCA, but not PCA, correlated with higher arterial blood pressure and poorer dynamic cerebral autoregulation. In healthy women with only moderately altered cerebral autoregulation, CBFV remained in the normal range. At both measurements, arterial blood pressure was higher in preeclamptic compared to healthy women. Women with preeclampsia had poorer cerebral autoregulation and an increased risk of transient cerebral hyperperfusion after delivery.

Delayed cord clamping is associated with improved dynamic cerebral autoregulation and decreased incidence of intraventricular hemorrhage in preterm infants.

Delayed cord clamping (DCC) improves neurologic outcomes in preterm infants through a reduction in intraventricular hemorrhage (IVH) incidence. The mechanism behind this neuroprotective effect is not known. Infants born <28 wk gestation were recruited for longitudinal monitoring. All infants underwent 72 h of synchronized near-infrared spectroscopy (NIRS) and mean arterial blood pressure (MABP) recording within 24 h of birth. Infants with DCC were compared with control infants with immediate cord clamping (ICC), controlling for severity of illness [clinical risk index for babies (CRIB-II) score], chorioamnionitis, antenatal steroids, sedation, inotropes, and delivery mode. Autoregulatory dampening was calculated as the transfer function gain coefficient between the MABP and NIRS signals. Forty-five infants were included (DCC; n = 15, paired 2:1 with ICC controls n = 30). ICC and DCC groups were similar including gestational age (25.5 vs. 25.2 wk, P = 0.48), birth weight (852.3 vs. 816.6 g, P = 0.73), percent female (40 vs. 40%, P = 0.75), and dopamine usage (27 vs. 23%, P = 1.00). There was a significant difference in IVH incidence between the DCC and ICC groups (20 vs. 50%, P = 0.04). Mean MABP was not different (35.9 vs. 35.1 mmHg, P = 0.44). Compared with the DCC group, the ICC group had diminished autoregulatory dampening capacity (-12.96 vs. -15.06 dB, P = 0.01), which remained significant when controlling for confounders. Dampening capacity was, in turn, strongly associated with decreased risk of IVH (odds ratio = 0.14, P < 0.01). The results of this pilot study demonstrate that DCC is associated with improved dynamic cerebral autoregulatory function and may be the mechanism behind the decreased incidence of IVH. NEW & NOTEWORTHY The neuroprotective mechanism of delayed cord clamping in premature infants is unclear. Delayed cord clamping was associated with improved cerebral autoregulatory function and a marked decrease in intraventricular hemorrhage (IVH). Improved dynamic cerebral autoregulation may decrease arterial baroreceptor sensitivity, thereby reducing the risk of IVH.

Impaired dynamic cerebral autoregulation in patients with cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) might disturb the sensitive mechanism of cerebral pressure autoregulation. This study examines whether dynamic cerebral autoregulation (CA) is impaired in the posterior or anterior circulation of CAA patients. Fifteen patients with known CAA on magnetic resonance imaging (MRI) and 14 age-matched controls were examined with transcranial Doppler. Dynamic CA was assessed in the middle (MCA) and posterior cerebral artery (PCA) via transfer function phase and gain during respiratory-induced 0.1 Hz oscillations of arterial pressure. Within the patient group, 4 patients showed additional microbleeds in the basal ganglia on the MRI performed within the study (pure CAA vs mixed microbleeds). PCA phase was significantly lower in patients compared with controls (p = 0.018), particularly in patients with pure CAA (p = 0.0034). MCA values showed a similar but non-significant trend towards lower phase in patients with pure CAA. Poorer phase was associated with a higher number of microbleeds on MRI (MCA r = −0.57, p = 0.027; PCA r = −0.52, p = 0.098) and superficial cortical siderosis (PCA: p = 0.0025). In conclusion, dynamic cerebral autoregulation is impaired in patients with CAA. The degree of impairment is associated with the extent of cerebral microbleeds.

Impact of Lifelong Exercise Training Dose on Ventricular-Arterial Coupling.

The dynamic Starling mechanism, as assessed by beat-by-beat changes in stroke volume and left ventricular end-diastolic pressure, reflects ventricular-arterial coupling. It deteriorates with age, and is preserved in highly trained masters athletes. Currently, it remains unclear how much exercise over a lifetime is necessary to preserve efficient ventricular-arterial coupling. The purpose of this study was to assess the dose-dependent relationship between lifelong exercise training and the dynamic Starling mechanism in healthy seniors. One hundred two seniors were recruited and stratified into 4 groups based on 25 years of exercise training history: sedentary subjects (n=27, <2 sessions/week), casual exercisers (n=25, 2-3 sessions/week), committed exercisers (n=25, 4-5 sessions/week), and competitive Masters Athletes (n=25, 6-7 sessions/week). The dynamic Starling mechanism was estimated by transfer function gain between beat-by-beat changes in diastolic pulmonary artery pressure, a surrogate for left ventricular end-diastolic pressure, and stroke volume index. The transfer function gain of pulmonary artery pressure-stroke volume index was markedly enhanced in committed and competitive exercisers compared with more sedentary seniors and correlated with higher peak oxygen uptake (Vo2) and lower left ventricular stiffness. The power spectral density of pulmonary artery pressure was greater in sedentary adults than in committed and competitive exercisers, whereas the power spectral density of stroke volume index was greater in competitive exercisers than in the other groups. There is a graded, dose-dependent improvement in ventricular-arterial coupling with increasing amounts of lifelong regular exercise in healthy older individuals. Our data suggest that the optimal dose of lifelong endurance exercise to preserve ventricular-arterial coupling with age appears to be at least 4 to 5 sessions per week.

Dynamic cerebral autoregulation after confinement in an isolated environment for 14\u2009days

BackgroundTo develop human space exploration, it is necessary to study the effects of an isolated and confined environment, as well as a microgravity environment, on cerebral circulation. However, no studies on cerebral circulation in an isolated and confined environment have been reported. Therefore, we investigated the effects of a 14-day period of confinement in an isolated environment on dynamic cerebral autoregulation.MethodsWe participated in an isolation and confinement experiment conducted by the Japan Aerospace Exploration Agency in 2016. Eight healthy males were isolated and confined in a facility for 14 days. Data were collected on the days immediately before and after confinement. Arterial blood pressure waveforms were obtained using a finger blood pressure monitor, and cerebral blood flow velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography for 6 min during quiet rest in a supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between spontaneous variability of beat-to-beat mean arterial blood pressure and mean cerebral blood flow velocity.ResultsTransfer function gain in the low- and high-frequency ranges increased significantly (0.54 ± 0.07 to 0.69 ± 0.09 cm/s/mmHg and 0.80 ± 0.05 to 0.92 ± 0.09 cm/s/mmHg, respectively) after the confinement.ConclusionThe increases observed in transfer function gain may be interpreted as indicating less suppressive capability against transmission from arterial blood pressure oscillation to cerebral blood flow velocity fluctuation. These results suggest that confinement in an isolated environment for 14 days may impair dynamic cerebral autoregulation.Trial registrationUMIN000020703, Registered 2016/01/22.

The impact of 2years of high-intensity exercise training on a model of integrated cardiovascular regulation.

Heart rate variability, a common and easily measured index of cardiovascular dynamics, is the output variable of complicated cardiovascular and respiratory control systems. Both neural and non-neural control mechanisms may contribute to changes in heart rate variability. We previously developed an innovative method using transfer function analysis to assess the effect of prolonged exercise training on integrated cardiovascular regulation. In the present study, we modified and applied this to investigate the effect of 2years of high-intensity training on circulatory components to tease out the primary effects of training. Our method incorporated the dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function. The dynamic Starling mechanism gain and arterial-cardiac baroreflex gain were significantly increased in the exercise group. These parameters remained unchanged in the controls. Conversely, neither group experienced a change in dynamic arterial elastance. The integrated cardiovascular regulation gain in the exercise group was 1.34-fold larger than that in the control group after the intervention. In these previously sedentary, otherwise healthy, middle-aged adults, 2 years of high-intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial-cardiac baroreflex sensitivity. Assessing the effects of exercise training on cardiovascular variability is challenging because of the complexity of multiple mechanisms. In a prospective, parallel-group, randomized controlled study, we examined the effect of 2years of high-intensity exercise training on integrated cardiovascular function, which incorporates the dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function. Sixty-one healthy participants (48% male, aged 53years, range 52-54years) were randomized to either 2years of exercise training (exercise group: n= 34) or control/yoga group (controls: n= 27). Before and after 2years, subjects underwent a 6min recording of beat-by-beat pulmonary artery diastolic pressure (PAD), stroke volume index (SVindex), systolic blood pressure (sBP) and RR interval measurements with controlled respiration at 0.2Hz. The dynamic Starling mechanism, dynamic arterial elastance and arterial-cardiac baroreflex function were calculated by transfer function gain between PAD and SVindex; SVindex and sBP; and sBP and RR interval, respectively. Fifty-three participants (controls: n= 25; exercise group: n= 28) completed the intervention. After 2years, the dynamic Starling mechanism gain (Group× Time interaction: P= 0.008) and the arterial-cardiac baroreflex gain (P= 0.005) were significantly increased in the exercise group but remained unchanged in the controls. There was no change in dynamic arterial elastance in either of the two groups. The integrated cardiovascular function gain in the exercise group increased 1.34-fold, whereas there was no change in the controls (P= 0.02). In these previously sedentary, otherwise healthy middle-aged adults, a 2year programme of high-intensity exercise training improved integrated cardiovascular regulation by enhancing the dynamic Starling mechanism and arterial-cardiac baroreflex sensitivity, without changing dynamic arterial elastance.

Patient-specific cranio-spinal compliance distribution using lumped-parameter model: its relation with ICP over a wide age range

BackgroundThe distribution of cranio-spinal compliance (CSC) in the brain and spinal cord is a fundamental question, as it would determine the overall role of the compartments in modulating ICP in healthy and diseased states. Invasive methods for measurement of CSC using infusion-based techniques provide overall CSC estimate, but not the individual sub-compartmental contribution. Additionally, the outcome of the infusion-based method depends on the infusion site and dynamics. This article presents a method to determine compliance distribution between the cranium and spinal canal non-invasively using data obtained from patients. We hypothesize that this CSC distribution is indicative of the ICP.MethodsWe propose a lumped-parameter model representing the hydro and hemodynamics of the cranio-spinal system. The input and output to the model are phase-contrast MRI derived volumetric transcranial blood flow measured in vivo, and CSF flow at the spinal cervical level, respectively. The novelty of the method lies in the model mathematics that predicts CSC distribution (that obeys the physical laws) from the system dc gain of the discrete-domain transfer function. 104 healthy individuals (48 males, 56 females, age 25.4 ± 14.9 years, range 3–60 years) without any history of neurological diseases, were used in the study. Non-invasive MR assisted estimate of ICP was calculated and compared with the cranial compliance to prove our hypothesis.ResultsA significant negative correlation was found between model-predicted cranial contribution to CSC and MR-ICP. The spinal canal provided majority of the compliance in all the age groups up to 40 years. However, no single sub-compartment provided majority of the compliance in 41–60 years age group. The cranial contribution to CSC and MR-ICP were significantly correlated with age, with gender not affecting the compliance distribution. Spinal contribution to CSC significantly positively correlated with CSF stroke volume.ConclusionsThis paper describes MRI-based non-invasive way to determine the cranio-spinal compliance distribution in the brain and spinal canal sub-compartments. The proposed mathematics makes the model always stable and within the physiological range. The model-derived cranial compliance was strongly negatively correlated to non-invasive MR-ICP data from 104 patients, indicating that compliance distribution plays a major role in modulating ICP.

Cerebral autoregulation in migraine with aura: A case control study.

Migraine with aura is independently associated with increased risk of ischemic stroke, especially in younger subjects. This association might be related to an impairment of cerebral autoregulation, which normally maintains cerebral blood flow independent of arterial blood pressure variations. Patients aged 30-55, fulfilling ICHD-3 beta criteria for migraine with aura, were prospectively enrolled and compared with gender- and age-matched healthy controls without a history of migraine. Patients and controls with a history of stroke or any disease potentially impairing cerebral autoregulation were excluded. We assessed cerebral autoregulation with two different methods: Transfer function analysis, and the correlation coefficient index Mx. The transfer function phase and gain reflect responses of cerebral blood flow velocities to relatively fast fluctuations of arterial blood pressure, whereas Mx also reflects responses to slower arterial blood pressure fluctuations. A total of 22 migraine with aura patients (median age [IQR]: 39.5 [12.5] years) and 22 controls (39 [9.75] years) were included. Transfer function parameters and Mx were not different between patients and controls. However, Mx was inversely correlated with age in patients (ρ = -0.567, p = 0.006) and not in controls (ρ = -0.084, p = 0.509). Mx was also inversely correlated with migraine with aura duration (ρ = -0.617, p = 0.002), suggesting improvement of cerebral autoregulation efficiency with disease duration. Cerebral autoregulation did not differ between patients and controls aged 30-55. However, cerebral autoregulation efficiency was strongly correlated with migraine with aura duration. Further studies in younger patients are needed to determine whether cerebral autoregulation is impaired early in the course of disease. NCT02708797.

Cerebral autoregulation and activity after propofol for endotracheal intubation in preterm neonates.

Despite increasing use of propofol in neonates, observations on cerebral effects are limited. To investigate cerebral autoregulation (CAR) and activity after propofol for endotracheal intubation in preterm neonates. Twenty-two neonates received propofol before intubation as part of a published dose-finding study. Mean arterial blood pressure (MABP), near-infrared spectroscopy-derived cerebral oxygenation (rScO2), and amplitude-integrated electroencephalography (aEEG) were analyzed until 180 min after propofol. CAR was expressed as transfer function (TF) gain, indicating % change in rScO2 per 1 mmHg change in MABP. Values exceeding mean TF gain + 2 standard deviations (SD)defined impaired CAR. After intubation with a median propofol dose of 1 (0.5-4.5) mg/kg, rScO2 remained stable during decreasing MABP. Mean (±SD) TF gain was 0.8 (±0.3)%/mmHg. Impaired CAR was identified in 1 and 5 patient(s) during drug-related hypotension and normal to raised MABP, respectively. Suppressed aEEG was observed up to 60 min after propofol. Drug-related hypotension and decreased cerebral activity after intubation with low propofol doses in preterm neonates were observed, without evidence of cerebral ischemic hypoxia. CAR remained intact during drug-related hypotension in 95.5% of patients. Cerebral monitoring including CAR clarifies the cerebral impact of MABP fluctuations.

Ivabradine preserves dynamic sympathetic control of heart rate despite inducing significant bradycardia in rats.

Ivabradine is a selective bradycardic agent that inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. HCN channels play a key role in mediating the positive chronotropic response to sympathetic nerve stimulation (SNS). We examined whether ivabradine would interfere with dynamic sympathetic control of heart rate (HR). The effect of intravenous ivabradine (2mg/kg, n = 7) or metoprolol (10mg/kg, n = 6) on the transfer function from SNS to HR was examined in anesthetized rats. Ivabradine preserved the asymptotic dynamic gain of the HR transfer function and nearly doubled the asymptotic dynamic gain of the transfer function from SNS to the R-R interval. In contrast, metoprolol abolished dynamic sympathetic control of HR. Preserved dynamic sympathetic control of HR, with coexisting bradycardia, may contribute to some of the beneficial effects of ivabradine previously reported in clinical application.

Cerebral blood flow regulation and cognitive function in women with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is associated with structural and functional alterations in a number of interacting brain regions, but the physiological mechanism for the high risk of cerebrovascular disease or impairment in brain function remains unknown. Women are more likely to develop PTSD after a trauma than men. We hypothesized that cerebral blood flow (CBF) regulation is impaired in women with PTSD, and it is associated with impairment in cognitive function. To test our hypothesis, we examined dynamic cerebral autoregulation (CA) and cognitive function by using a transfer function analysis between arterial pressure and middle cerebral artery blood velocity and the Stroop Color and Word test (SCWT), respectively. We did not observe any different responses in these hemodynamic variables between women with PTSD ( n = 15) and healthy counterparts (all women; n = 8). Cognitive function was impaired in women with PTSD; specifically, reaction time for the neutral task of SCWT was longer in women with PTSD compared with healthy counterparts ( P = 0.011), but this cognitive dysfunction was not affected by orthostatic stress. On the other hand, transfer function phase, gain, and coherence were not different between groups in either the supine or head-up tilt (60°) position, or even during the cognitive challenge, indicating that dynamic CA was well maintained in women with PTSD. In addition, there was no relationship between cognitive function and dynamic CA. These findings suggest that PTSD-related cognitive dysfunction may not be due to compromised CBF regulation. NEW & NOTEWORTHY Cognitive function was impaired; however, dynamic cerebral autoregulation (CA) as an index of cerebral blood flow regulation was not impaired during supine and 60° head-up tilt in women with PTSD compared with healthy females. In addition, there was no relationship between cognitive function and dynamic CA. These findings suggest that the mechanism of PTSD-related cognitive dysfunction may not be due to CBF regulation.

Incomplete recovery of cerebral blood flow dynamics in sufficiently treated high blood pressure.

Objective:Whether cerebrovascular regulation is different in patients with controlled high blood pressure (HBP) with and without small vessel disease (SVD).Methods:Sixty-seven healthy controls (mean age ± SD, 45 ± 16 years; 30 women, 37 men) and 40 patients (mean age, 64 ± 13 years; 14 women, 26 men) with HBP and different stages of SVD, underwent simultaneous recordings of the spontaneous fluctuations of BP, blood flow velocity (CBFV) in both middle cerebral arteries (MCA), and of end-tidal CO2 (ETCO2). Coherence and transfer function gain and phase between BP and CBFV were assessed in the frequency ranges of VLF (0.02–0.07 Hz), low frequency (0.07–0.15), and high frequency (>0.15). BP SD indicated BP variability (BPV).Results:In controls (BP, 86 ± 13 mmHg; ETCO2, 39 ± 4 mmHg; BPV, 15 ± 6 mmHg), gain, phase and coherence were not age-dependent in simple or a multiple regression models. BPV correlated significantly in both MCAs with gain in low frequency and high frequency, and with phase in VLF and high frequency. In patients (BP, 91 ± 16 mmHg, ETCO2, 39 ± 4 mmHg, BPV 18 ± 5 mmHg), only gain showed some differences between different SVD groups. Comparing all patients with 25 controls of similar age and sex, patients exhibited significantly (P < 0.05–P < 0.005): increased coherence and gain in VLF, decreased phase in VLF and low frequency, correlations between BPV with phase in low frequency (left) and with gain in VLF (left) and in high frequency (left and right).Conclusion:Phase seems an age independent autoregulatory index. In controlled HBP, CBF regulation is degraded at longlasting CBF changes; BPV effects lose their physiological bilateral distribution.

Comparison of Different Strategies to Assess Cardiac Baroreflex Sensitivity Based on Transfer Function Technique in Patients Undergoing General Anesthesia.

Baroreflex sensitivity (BRS) can be noninvasively assessed from heart period (HP) and arterial pressure (AP) variability series via the estimation of the gain of the transfer function (TF) in the low frequency (LF, 0.04-0.15 Hz) band. However, different strategies can be adopted to pick the value of the TF gain and different fiducial AP values can be considered. In this study we compared different strategies to reduce the TF gain into a unique maker: i) sampling the TF gain in correspondence of the maximum of the HP-AP squared coherence; ii) sampling the TF gain at the weighted average of the central frequencies of AP spectral components; iii) calculating the average of the TF gain in the LF band. Indexes were computed using alternatively systolic AP (SAP) or diastolic AP (DAP) series in combination with HP. Results were obtained in 129 patients undergoing coronary artery bypass graft surgery before (PRE) and after (POST) the induction of general anesthesia with propofol and remifentanil. The reduction of BRS during general anesthesia is expected as a result of overall depression of the cardiovascular control even in this group of pathological subjects already featuring a low BRS before general anesthesia induction. We found that the expected decrease of BRS was observed regardless of the strategy using DAP. Moreover, regardless of series (i.e., SAP or DAP), the sampling of TF gain at the weighted average of the central frequencies of the AP spectral components has the greatest statistical power in distinguishing the two experimental conditions. We recommend the use of this strategy in assessing BRS via TF analysis and a more frequent exploitation of the DAP series.

No long-term impairment of cerebral autoregulation after preeclampsia.

Preeclampsia is a pregnancy-related hypertensive disorder with strongly impaired cerebral autoregulation in the acute stage. A history of preeclampsia is an independent cardiovascular and cerebrovascular risk factor. It is unclear whether impaired cerebral autoregulation persists after preeclampsia and thus contributes to the known increased cerebrovascular morbidity. Using transcranial Doppler, we compared cerebral hemodynamics and dynamic cerebral autoregulation of 25 women with a history of severe preeclampsia and 25 healthy mothers, on average 2-3 years postpartum. Mean arterial blood pressure (MAP) and cerebral blood flow velocities (CBFV) in the middle and posterior cerebral artery were recorded at rest, dynamic cerebral autoregulation was assessed via transfer function phase and gain between oscillations of CBFV and MAP during regular breathing at 0.1 Hz. MAP and body mass index were higher in former preeclamptic women compared with healthy mothers (p-value <0.001 and 0.006, respectively). CBFV in the middle cerebral artery was slightly increased in former preeclamptic women compared with healthy mothers (p-value 0.004), intima-media thickness (IMT) of the common carotid artery was higher by trend (p-value 0.065). Dynamic cerebral autoregulation was not impaired in women with a history of preeclampsia, phase even tended to be higher than in healthy mothers. Dynamic cerebral autoregulation is not persistently impaired in women after severe preeclampsia. Long-term cerebrovascular changes rather result from a higher incidence of cerebrovascular risk factors in women with a history of preeclampsia.

Dynamic Regulation of Cerebral Blood Flow in Patients With Alzheimer Disease.

Cerebral autoregulation and baroreflex sensitivity are key mechanisms that maintain cerebral blood flow. This study assessed whether these control mechanisms are affected in patients with dementia and mild cognitive impairment due to Alzheimer disease, as this would increase the risks of antihypertensive treatment. We studied 53 patients with dementia (73.1 years [95% confidence interval (CI), 71.4-74.8]), 37 patients with mild cognitive impairment (69.2 years [95% CI, 66.4-72.0]), and 47 controls (69.4 years [95% CI, 68.3-70.5]). Beat-to-beat blood pressure (photoplethysmography), heart rate, and cerebral blood flow velocity (transcranial Doppler) were measured during 5-minute rest (sitting) and 5 minutes of orthostatic challenges, using repeated sit-to-stand maneuvers. Cerebral autoregulation was assessed using transfer function analysis and the autoregulatory index. Baroreflex sensitivity was estimated with transfer function analysis and by calculating the heart rate response to blood pressure changes during the orthostatic challenges. Dementia patients had the lowest cerebral blood flow velocity (P=0.004). During rest, neither transfer function analysis nor the autoregulatory index indicated impairments in cerebral autoregulation. During the orthostatic challenges, higher autoregulatory index (P=0.011) and lower transfer function gain (P=0.017), indicating better cerebral autoregulation, were found in dementia (4.56 arb. unit [95% CI, 4.14-4.97]; 0.59 cm/s per mm Hg [95% CI, 0.51-0.66]) and mild cognitive impairment (4.59 arb. unit [95% CI, 4.04-5.13]; 0.51 cm/s per mm Hg [95% CI, 0.44-0.59]) compared with controls (3.71 arb. unit [95% CI, 3.35-4.07]; 0.67 cm/s per mm Hg [95% CI, 0.59-0.74]). Baroreflex sensitivity measures did not differ between groups. In conclusion, the key mechanisms to control blood pressure and cerebral blood flow are not reduced in 2 stages of Alzheimer disease compared with controls, both in rest and during orthostatic changes that reflect daily life challenges.

Measuring Near-Infrared Spectroscopy Derived Cerebral Autoregulation in Neonates: From Research Tool Toward Bedside Multimodal Monitoring.

Introduction: Cerebral autoregulation (CAR), the ability of the human body to maintain cerebral blood flow (CBF) in a wide range of perfusion pressures, can be calculated by describing the relation between arterial blood pressure (ABP) and cerebral oxygen saturation measured by near-infrared spectroscopy (NIRS). In literature, disturbed CAR is described in different patient groups, using multiple measurement techniques and mathematical models. Furthermore, it is unclear to what extent cerebral pathology and outcome can be explained by impaired CAR.Aim and methods: In order to summarize CAR studies using NIRS in neonates, a systematic review was performed in the PUBMED and EMBASE database. To provide a general overview of the clinical framework used to study CAR, the different preprocessing methods and mathematical models are described and explained. Furthermore, patient characteristics, definition of impaired CAR and the outcome according to this definition is described organized for the different patient groups.Results: Forty-six articles were included in this review. Four patient groups were established: preterm infants during the transitional period, neonates receiving specific medication/treatment, neonates with congenital heart disease and neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Correlation, coherence and transfer function (TF) gain are the mathematical models most frequently used to describe CAR. The definition of impaired CAR is depending on the mathematical model used. The incidence of intraventricular hemorrhage in preterm infants is the outcome variable most frequently correlated with impaired CAR. Hypotension, disease severity, dopamine treatment, injury on magnetic resonance imaging (MRI) and long term outcome are associated with impaired CAR. Prospective interventional studies are lacking in all research areas.Discussion and conclusion: NIRS derived CAR measurement is an important research tool to improve knowledge about central hemodynamic fluctuations during the transitional period, cerebral pharmacodynamics of frequently used medication (sedatives-inotropes) and cerebral effects of specific therapies in neonatology. Uniformity regarding measurement techniques and mathematical models is needed. Multimodal monitoring databases of neonatal intensive care patients of multiple centers, together with identical outcome parameters are needed to compare different techniques and make progress in this field. Real-time bedside monitoring of CAR, together with conventional monitoring, seems a promising technique to improve individual patient care.

Cerebral Autoregulation Is Impaired In Recurrent Syncope Patients

PURPOSE: Cerebral autoregulation is a homeostatic mechanism that serves to maintain cerebral blood flow constant over a wide range of perfusion pressure. Syncope is thought to be caused by cerebral hypoperfusion due to the transient blood pressure drop, and thus impairment of cerebral autoregulation may facilitate syncope. A previous study has reported that a past history of syncope is a strong predictor of future syncope recurrence. However, it is unclear whether impaired cerebral autoregulation would be related with recurrent syncope. The purpose of this study was to test our hypothesis that cerebral autoregulation would be impaired in syncope patients with a past history of syncope as compared with those for the first time. METHODS: We evaluated cerebral autoregulation in 24 syncope patients for the first time (age; 64±19 years old, male/ female; 15/9) and 20 syncope patients with a past history of syncope (age; 52±26 years old, male/female; 11/9). In patients with recurrent syncope, the number of past syncope was 2.9±1.6 times (range 2-7 times). Middle cerebral artery mean blood flow velocity (MCA Vmean) and mean arterial pressure (MAP) were measured by transcranial Doppler ultrasound and tonometry on right radial artery for 3 min in the supine position. In offline analysis after the measurement, the transfer function gain between MAP and MCA Vmean were calculated at very low frequency (0.023-0.07 Hz, VLF) and low frequency (0.07-0.2 Hz, LF) ranges to estimate dynamic cerebral autoregulation. RESULTS: LF gain did not differ between syncope patients with a past history of syncope and those for the first time (P=0.23). In contrast, VLF gain was significantly higher in patients with a past history of syncope than in those for the first time (1.81±1.17 cm/s/mmHg vs. 1.09±0.65 cm/s/mmHg, P=0.02). CONCLUSIONS: These data suggest that impaired cerebral autoregulation at least in part explains physiological mechanisms underlying recurrent syncope.

Dynamic Cerebral Autoregulation Impairment Persists Past Resolution of Symptoms in Collegiate Athletes Following Concussion

ObjectivesDespite 3.8 million concussions occurring annually in the United States, the pathophysiological sequelae of the injury are still poorly understood. Animal and human studies have consistently reported deficits in cerebral blood flow (CBF) following concussion suggesting impairments in CBF regulation. Reductions in CBF are also associated with functional outcomes. The purpose of the study was to examine dynamic cerebral autoregulation (dCA) in an ongoing prospective cohort of collegiate athletes 3 days, 21 days, and 90 days following a concussion and compare them with non‐injured controls.Materials and MethodsTwenty‐seven NCAA and recreational athletes (20±1 years) with a physician diagnosed sports‐related concussions were enrolled in the study. For the injured athletes, data was collected on days 3,21, and 90 following concussion. Twenty‐five age and sports matched non‐injured controls (20±1 years) were also enrolled. For non‐injured controls, data was collected at one time point. Symptom number and severity was measured using the Sports Concussion Assessment Tool (SCAT‐3). Depression scores were assessed with Patient Health Questionnaire‐9 (PHQ‐9). Continuous mean arterial blood pressure (MBP) was obtained with finger photoplethysmography and middle cerebral artery blood flow velocity (MCAV) was obtained with a 2 MHz transcranial Doppler ultrasonography while subjects were seated in an upright position. dCA was estimated from transfer function (Tf) analysis of beat‐to‐beat spontaneous fluctuations in MBP and MCAV within the low (LF, 0.07–0.20 Hz) and high (HF, 0.20–0.35 Hz) frequency ranges. Effective dCA would attenuate spontaneous changes in MCAV in response to variations in MBP, which would correspond to relatively low transfer function gain. Independent and paired t‐tests were used to compare dCA between days 3, 21, and 90 following concussion with the non‐injured controls.ResultsCompare to the controls, concussed athletes exhibited greater symptom number on day‐3 (12.2±6.8 vs. 2.4±3.4; p&lt;0.001) and higher PHQ‐9 score (8.7±5.6 vs. 2.1±2.1; p&lt;0.001). LF Tf gain was higher on day‐3 (1.26±0.34U vs. 1.04±0.28U; p=0.016) compared to the controls. LF Tf gain continued to be high on day‐21 (1.30±0.45U; p=0.025) compared to the non‐injured controls despite no differences in symptoms number or depression scores between the groups. LF Tf gain was comparable to the controls on day‐90.ConclusionsDynamic cerebral autoregulation appears to be impaired at least up to 21 days following concussion despite improvement in symptom and depression. Cerebral autoregulation estimated from transcranial Doppler ultrasonography may be useful as a potential vascular biomarker for return‐to‐play decisions following a concussion preventing the risk of second‐impact syndrome.Support or Funding InformationThis work was supported by SMU University Research Council Grant, Spring 2015 &amp; Texas Institute for Brain Injury and Repair (TIBIR) Pilot Grant 2016.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Chronic kidney disease and poor outcomes in ischemic stroke: is impaired cerebral autoregulation the missing link?

BackgroundChronic kidney disease increases stroke incidence and severity but the mechanisms behind this cerebro-renal interaction are mostly unexplored. Since both vascular beds share similar features, microvascular dysfunction could be the possible missing link. Therefore, we examined the relationship between renal function and cerebral autoregulation in the early hours post ischemia and its impact on outcome.MethodsWe enrolled 46 ischemic strokes (middle cerebral artery). Dynamic cerebral autoregulation was assessed by transfer function (coherence, phase and gain) of spontaneous blood pressure oscillations to blood flow velocity within 6 h from symptom-onset. Estimated glomerular filtration rate (eGFR) was calculated. Hemorrhagic transformation (HT) and white matter lesions (WML) were collected from computed tomography performed at presentation and 24 h. Outcome was evaluated with modified Rankin Scale at 3 months.ResultsHigh gain (less effective autoregulation) was correlated with lower eGFR irrespective of infarct side (p < 0.05). Both lower eGFR and higher gain correlated with WML grade (p < 0.05). Lower eGFR and increased gain, alone and in combination, progressively reduced the odds of a good functional outcome [ipsilateral OR = 4.39 (CI95% 3.15–25.6), p = 0.019; contralateral OR = 8.15 (CI95% 4.15–15.6), p = 0.002] and increased risk of HT [ipsilateral OR = 3.48 (CI95% 0.60–24.0), p = 0.132; contralateral OR = 6.43 (CI95% 1.40–32.1), p = 0.034].ConclusionsLower renal function correlates with less effective dynamic cerebral autoregulation in acute ischemic stroke, both predicting a bad outcome. The evaluation of serum biomarkers of renal dysfunction could have interest in the future for assessing cerebral microvascular risk and relationship with stroke complications.

Effect of acute hypoxemia on cerebral blood flow velocity control during lower body negative pressure.

The ability to maintain adequate cerebral blood flow and oxygenation determines tolerance to central hypovolemia. We tested the hypothesis that acute hypoxemia during simulated blood loss in humans would cause impairments in cerebral blood flow control. Ten healthy subjects (32 ± 6 years, BMI 27 ± 2 kg·m−2) were exposed to stepwise lower body negative pressure (LBNP, 5 min at 0, −15, −30, and −45 mmHg) during both normoxia and hypoxia (FiO2 = 0.12–0.15 O2 titrated to an SaO2 of ~85%). Physiological responses during both protocols were expressed as absolute changes from baseline, one subject was excluded from analysis due to presyncope during the first stage of LBNP during hypoxia. LBNP induced greater reductions in mean arterial pressure during hypoxia versus normoxia (MAP, at −45 mmHg: −20 ± 3 vs. −5 ± 3 mmHg, P < 0.01). Despite differences in MAP, middle cerebral artery velocity responses (MCAv) were similar between protocols (P = 0.41) due to increased cerebrovascular conductance index (CVCi) during hypoxia (main effect, P = 0.04). Low frequency MAP (at −45 mmHg: 17 ± 5 vs. 0 ± 5 mmHg2, P = 0.01) and MCAv (at −45 mmHg: 4 ± 2 vs. −1 ± 1 cm·s−2, P = 0.04) spectral power density, as well as low frequency MAP‐mean MCAv transfer function gain (at −30 mmHg: 0.09 ± 0.06 vs. −0.07 ± 0.06 cm·s−1·mmHg−1, P = 0.04) increased more during hypoxia versus normoxia. Contrary to our hypothesis, these findings support the notion that cerebral blood flow control is not impaired during exposure to acute hypoxia and progressive central hypovolemia despite lower MAP as a result of compensated increases in cerebral conductance and flow variability.