Arterial Blood Pressure Fluctuations Research Articles

A multi-objective optimisation approach for the linear modelling of cerebral autoregulation system

Objective:Dynamic cerebral autoregulation (dCA) has been addressed through different approaches for discriminating between normal and impaired conditions based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CF). This work presents a novel multi-objective optimisation (MO) approach for finding good configurations of a cerebrovascular resistance-compliance model. Methods:Data from twenty-nine subjects under normo and hypercapnic (5% CO2 in air) conditions was used. Cerebrovascular resistance and vessel compliance models with ABP as input and CF velocity as output were fitted using a MO approach, considering fitting Pearson’s correlation and error. Results:MO approach finds better model configurations than the single-objective (SO) approach, especially for hypercapnic conditions. In addition, the Pareto-optimal front from the multi-objective approach enables new information on dCA, reflecting a higher contribution of myogenic mechanism for explaining dCA impairment.

Effect of lidocaine on intraoperative blood pressure variability in patients undergoing major vascular surgery

BackgroundDynamic fluctuations of arterial blood pressure known as blood pressure variability (BPV) may have short and long-term undesirable consequences. During surgical procedures blood pressure is usually measured in equal intervals allowing to assess its intraoperative variability, which significance for peri and post-operative period is still under debate. Lidocaine has positive cardiovascular effects, which may go beyond its antiarrhythmic activity. The aim of the study was to verify whether the use of intravenous lidocaine may affect intraoperative BPV in patients undergoing major vascular procedures.MethodsWe performed a post-hoc analysis of the data collected during the previous randomized clinical trial by Gajniak et al. In the original study patients undergoing elective abdominal aorta and/or iliac arteries open surgery were randomized into two groups to receive intravenous infusion of 1% lidocaine or placebo at the same infusion rate based on ideal body weight, in concomitance with general anesthesia. We analyzed systolic (SBP), diastolic (DBP) and mean arterial blood (MAP) pressure recorded in 5-minute intervals (from the first measurement before induction of general anaesthesia until the last after emergence from anaesthesia). Blood pressure variability was then calculated for SBP and MAP, and expressed as: standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and coefficient of hemodynamic stability (C10%), and compared between both groups.ResultsAll calculated indexes were comparable between groups. In the lidocaine and placebo groups systolic blood pressure SD, CV, AVR and C10% were 20.17 vs. 19.28, 16.40 vs. 15.64, 14.74 vs. 14.08 and 0.45 vs. 0.45 respectively. No differences were observed regarding type of surgery, operating and anaesthetic time, administration of vasoactive agents and intravenous fluids, including blood products.ConclusionIn high-risk vascular surgery performed under general anesthesia, lidocaine infusion had no effect on arterial blood pressure variability.Trial registrationClinicalTrials.gov; NCT04691726 post-hoc analysis; date of registration 31/12/2020.

Non-invasive estimation of arterial blood pressure fluctuations using a peripheral photoplethysmograph inside the MRI scanner.

The blood-oxygen-level-dependent (BOLD) signal measured by functional magnetic resonance imaging (fMRI) is modulated by neural activity through the neurovascular coupling effect, as well as non-neural factors of physiological origin such as heart rate, respiration, and arterial blood pressure (ABP). While the former two effects have been previously characterized, the modulation of the BOLD signal by ABP fluctuations is still poorly understood. This is largely due to the difficulty of obtaining reliable ABP measurements in the MRI environment. Here, we propose a combined experimental and mathematical modeling framework to estimate ABP fluctuations inside the MRI scanner using photoplethysmography (PPG). Specifically, we used concurrent PPG and ABP measurements obtained outside the scanner to train the mathematical model and applied it to PPG measurements obtained inside the MRI scanner. Our results suggest good agreement between the model-predicted and experimentally measured ABP fluctuations and region specific correlations with the BOLD fluctuations.

Revealing the coupling directionality and synchronization between time series from physiological data by analysis of joint recurrences

We applied methods for determining the recurrence based phase synchronization index and the coupling directionality based on conditional probabilities of recurrence to analyze the direction of coupling and synchronization of time series obtained from experimental data. The activity of brain neurons, fluctuations in arterial blood pressure, and the respiratory rhythm of anesthetized rats were used as experimental data. For the first time, variants of changing the direction of the coupling between the analyzed time series before and during pain exposure were revealed. The relationship of pain exposure with the adjustment of the frequency of the variability of neuron activity of the brain to the frequency of the variability of arterial blood pressure or with the adjustment of the frequency of the variability of blood pressure to the respiratory rhythm with the subsequent occurrence of phase synchronization has been established.

Assessment of baroreflex sensitivity during isometric handgrip exercise and oscillatory lower body negative pressure

ObjectivesBaroreflex sensitivity (BRS) is an estimate of autonomic control of cardiovascular system via the baroreflex arc. It has been suggested that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain, which facilitates the simultaneous rise in blood pressure (BP) and heart rate during the exercise. This study investigated the effects of isometric handgrip exercise (IHE) on baroreflex gain and frequency dependence of baroreflex sensitivity while fluctuations in arterial BP were generated. MethodsThirteen healthy men performed IHE at 20% and 30% of their maximum voluntary contraction (MVC), while oscillatory lower body negative pressure (OLBNP) of 40 mmHg was applied in 0.1 and 0.25 Hz frequencies. ResultsCompared to the OLBNP at 0.25 Hz frequency alone, the baroreflex gain for diastolic BP (DBP) was significantly reduced with the addition of IHE at 20% and 30% of MVC in the high frequency band. At rest (without IHE and OLBNP) the baroreflex gain was significantly more in the high frequency band for DBP, but the baroreflex gain for DBP was not significantly different when IHE + OLBNP were applied at 20% and 30% of MVC in both frequencies. ConclusionsThe significant reduction of DBP baroreflex gain with the addition of graded IHE might indicate that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain at a high frequency band (0.25 Hz). The frequency-dependent phenomenon of BRS was altered when IHE and OLBNP were applied, meaning that the frequency dependence of BRS was nullified during IHE.

Multi‐center study reveals impairment of cortical tissue oxygenation during rising blood CO2 tension in MCI and AD patients

AbstractBackgroundAn ongoing multi‐center study of a consortium of Alzheimer’s Disease Centers in Los Angeles (USC), Dallas (UT‐SWMC) and Kansas City (KUMC) has explored quantitatively the dynamics of the homeostatic mechanism that maintains adequate cortical tissue oxygenation during a rise in blood CO2 tension. The results from cognitively normal subjects and MCI/AD patients were compared to assess differences in the dynamics of this important homeostatic mechanism.MethodQuantification of the dynamics of cortical tissue oxygenation was achieved through extraction of predictive models from five‐minute data‐records of spontaneous fluctuations in cortical tissue oxygenation (CTO), measured non‐invasively via near infrared spectroscopy at the prefrontal cortex, and the associated fluctuations in arterial blood pressure (ABP) and end‐tidal CO2 (etCO2). Using a novel kernel‐based modeling methodology, we analyzed the time‐series data from 25 MCI patients, 7 AD patients and 45 age‐matched cognitively normal controls (NC) and obtained predictive models of the dynamic effects of ABP and etCO2 (viewed as a proxy for blood CO2 tension) upon CTO. These predictive models were used to quantify the dynamics of cortical CO2 reactivity (CCR) in each participant, as the time‐average of the model‐predicted CTO response to unit‐step etCO2 change over the first 30 sec. The obtained CCR indices were used to evaluate the differences between NC and MCI/AD patients.ResultThe obtained CCR indices were significantly different for the 32 patients (MCI and AD lumped together due to small number of AD) vs. 45 age‐matched controls (p= 0.0083), with respective mean (SD): 0.014 (0.108) vs ‐0.059 (0.119). This is illustrated in Figure 1, where the average model‐predicted CTO responses to a unit‐step change of etCO2 are shown for 32 MCI/AD patients (red line) and 45 controls (blue line). Note the negative values of the average CTO response for patients (red line) to unit‐step increase of etCO2 that indicates polarity reversal of the normal CO2 vasomotor reactivity (blue line).ConclusionQuantitative analysis of cortical oxygenation dynamics under resting spontaneous conditions in 32 MCI/AD patients relative to 45 age‐matched controls revealed a significant impairment of the homeostatic mechanism that maintains adequate oxygenation of cortical tissue during a rise in blood CO2 tension.

Directional sensitivity of dynamic cerebral autoregulation during spontaneous fluctuations in arterial blood pressure at rest

Directional sensitivity, the more efficient response of cerebral autoregulation to increases, compared to decreases, in mean arterial pressure (MAP), has been demonstrated with repeated squat-stand maneuvers (SSM). In 43 healthy subjects (26 male, 23.1 ± 4.2 years old), five min. recordings of cerebral blood velocity (bilateral Doppler ultrasound), MAP (Finometer), end-tidal CO2 (capnograph), and heart rate (ECG) were obtained during sitting (SIT), standing (STA) and SSM. A new analytical procedure, based on autoregressive-moving average models, allowed distinct estimates of the autoregulation index (ARI) by separating the MAP signal into its positive (MAP+D) and negative (MAP−D) derivatives. ARI+D was higher than ARI−D (p < 0.0001), SIT: 5.61 ± 1.58 vs 4.31 ± 2.16; STA: 5.70 ± 1.24 vs 4.63 ± 1.92; SSM: 4.70 ± 1.11 vs 3.31 ± 1.53, but the difference ARI+D–ARI−D was not influenced by the condition. A bootstrap procedure determined the critical number of subjects needed to identify a significant difference between ARI+D and ARI−D, corresponding to 24, 37 and 38 subjects, respectively, for SSM, STA and SIT. Further investigations are needed on the influences of sex, aging and other phenotypical characteristics on the phenomenon of directional sensitivity of dynamic autoregulation.

Cardiovascular autonomic nervous function in 7–12 years old children conceived naturally or by ART with frozen and fresh embryo transfer

Abstract Background Cardiovascular autonomic nervous functions (CANF) exert important homeostatic mechanisms to prevent major arterial blood pressure fluctuations by adjusting heart rate (HR), cardiac contractility, and peripheral vascular tone. Children conceived by assisted reproductive technologies (ART) are at risk of increased carotid intima-media thickness, insulin resistance, arterial stiffness, and hypertension. CANF is impaired in children with obesity and diabetes mellitus, and conductance artery stiffness is documented to influence CANF. CANF may therefore be hypothetized to be impaired in children conceived by ART. Purpose This is the first study to investigate whether children conceived by ART have impaired CANF as compared to naturally conceived children. Method CANF was studied in 105 singletons aged 7–12 years conceived naturally (NC, N=33) or by ART (frozen embryo transfer (FET, N=34) and fresh embryo transfer (Fresh ET, N=38)). CANF was evaluated with continuous non-invasive hemodynamic measurements (Finapres®) by the HR and blood pressure changes seen relative to rest during active standing, deep breathing and Valsalva, respectively. Results The descriptive data showed no difference in CANF measurements between our study groups (Table 1). In the multivariate analysis, only the Valsalva HR-ratio to rest was significantly higher in children conceived by FET as compared to NC children after adjustments for age, sex, BMI and maternal age at delivery (Figure 1). For all meaures, the effect size (Hedges d) ranged from 0.02 to 0.48. Conclusion In this study only the Valsalva HR-response between FET and NC groups were statistically significant after adjustment for confounders, and in general effect sizes were small. Our study suggests that children conceived by ART do not have a significantly impaired cardiovascular autonomic nervous function as compared to naturally conceived children. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation

Optimal duration of the apnea test for determining brain death: Benefit of the short-term apnea test.

The criteria for brain death determination have not been unified globally, and there is no global consensus on the apnea test, which is essential for determining brain death. Since the apnea test is associated with many complications, we aimed to determine an optimal duration of the apnea test. We analyzed the results of the apnea test performed for brain death determination between August 2013 and February 2021 at a single institution in South Korea. Elevations in the partial pressure of carbon dioxide and mean arterial blood pressure fluctuations over time in the apnea test were recorded. In the 1st and 2nd tests, the mean partial pressure of carbon dioxide increased by more than 20 mmHg at 3 min after the apnea test compared to before the test (P < 0.05). At 4 min in the 1st test and 5 min in the 2nd test, the partial pressure of carbon dioxide exceeded 60 mmHg (P < 0.05). The fluctuation in the mean arterial blood pressure observed for 5 min during the apnea test was not significant. There was no significant fluctuation in the mean arterial blood pressure over time in the apnea test between patients with normal chest radiography findings and those with abnormal chest radiography findings (P = 0.888). Our study proposes that a short-term apnea test protocol is valid for the preservation of organs for donation.

P-772 Cardiovascular autonomic nervous function in singletons conceived after ART with frozen and fresh embryo transfer compared to naturally conceived children

Abstract Study question Do children conceived after assisted reproductive technologies (ART) with frozen or fresh embryo transfer have altered cardiovascular autonomic nervous function compared to naturally conceived children? Summary answer Cardiovascular autonomic nervous function was comparable in singletons conceived after ART with frozen or fresh embryo transfer, and naturally conceived children. What is known already Cardiovascular autonomic nervous function (CANF) exert important homeostatic mechanisms to prevent major arterial blood pressure fluctuations by adjusting heart rate, cardiac contractility, and peripheral vascular tone. CANF is impaired in children with obesity and diabetes mellitus, and conductance artery stiffness is documented to influence CANF. Previous studies have reported that children conceived after ART are at risk of increased carotid intima-media thickness; insulin resistance; arterial stiffness; and hypertension. This is the first study to investigate CANF in children conceived after ART. Study design, size, duration CANF was studied in 110 singletons aged 7-12 years conceived after frozen embryo transfer (FET, N = 35), fresh embryo transfer (fresh-ET, N = 39) or natural conception (NC, N = 36). Children were born between 2009 and 2013. This study was conducted between June 2019 and October 2021. Participants/materials, setting, methods Participants were identified through the Danish IVF and Medical Birth Registries. CANF was evaluated by heart rate (HR) changes (ratio to rest) during deep breathing; Valsalva; and active stand test with continuous non-invasive hemodynamic measurements. Anthropometric measures, fasting blood samples, and maternal questionnaires were collected. Neonatal and maternal pregnancy data were collected from the Medical Birth Registry. Children with a history of congenital heart disease or mothers with gestational diabetes or diabetes mellitus were excluded. Main results and the role of chance A total of 110 singletons with a median age of 9.0 years were included in this study. We found no significant associations between conception method and our measures of CANF. For FET, fresh-ET, and NC, respectively, the HR-ratio for deep breathing was 1.62 (0.2 SD), 1.62 (0.16) and 1.63 (0.17) (ANOVA-P = 0.97). For Valsalva, the HR-ratio was 1.97 (0.4), 1.88 (0.41) and 1.63 (0.17), respectively (ANOVA-P = 0.24). For the active stand test, the HR-ratio was 1.43 (0.17), 1.41 (0.2) and 1.43 (0.19), respectively (ANOVA-P = 0.91). Associations remained non-significant after adjustment for age, sex, body surface area, body mass index, and mean arterial pressure. In the multivariate analysis, several other factors were significantly associated with HR-ratio for deep breathing: age (β = -0.06, P = 0.03), body surface area (β = 0.79, P = 0.01), body mass index (β = -0.03, P = 0.04), and mean arterial pressure (β =-0.01, P = 0.03), but not with other measures of CANF. All data for CANF were within reference limits. Also, mothers in the ART groups were older at childbirth than NC group as expected. No significant differences were observed in clinical characteristics, including neonatal and other maternal data. Limitations, reasons for caution This study is limited by its observational design to draw any firm conclusion on causality. Also, it is a limitation that the pubertal status was not systematically assessed as pubertal hormones may play a role in CANF. Wider implications of the findings This study contributes to the current knowledge about cardiovascular health risks in ART children. Reassuringly, this study found that children conceived after ART (frozen or fresh-ET) did not exhibit impaired cardiovascular autonomic nervous function compared to naturally conceived children. Trial registration number NCT03719703

Rhythmic firing of neurons in the medulla of conscious freely behaving rats: rhythmic coupling with baroreceptor input.

Recent investigations emphasized the importance of neural control of cardiovascular adjustments in complex behaviors, including stress, exercise, arousal, sleep-wake states, and different tasks. Baroreceptor feedback is an essential component of this system acting on different time scales from maintaining stable levels of cardiovascular parameters on the long-term to rapid alterations according to behavior. The baroreceptor input is essentially rhythmic, reflecting periodic fluctuations in arterial blood pressure. Cardiac rhythm is a prominent feature of the autonomic control system, present on different levels, including neuron activity in central circuits. The mechanism of rhythmic entrainment of neuron firing by the baroreceptor input was studied in great detail under anesthesia, but recordings of sympathetic-related neuron firing in freely moving animals remain extremely scarce. In this study, we recorded multiple single neuron activity in the reticular formation of the medulla in freely moving rats during natural behavior. Neurons firing in synchrony with the cardiac rhythm were detected in each experiment (n = 4). In agreement with prior observations in anesthetized cats, we found that neurons in this area exhibited high neuron-to-neuron variability and temporal flexibility in their coupling to cardiac rhythm in freely moving rats, as well. This included firing in bursts at multiples of cardiac cycles, but not directly coupled to the heartbeat, supporting the concept of baroreceptor input entraining intrinsic neural oscillations rather than imposing a rhythm of solely external origin on these networks. It may also point to a mechanism of maintaining the basic characteristics of sympathetic neuron activity, i.e., burst discharge and cardiac-related rhythmicity, on the background of behavior-related adjustments in their firing rate.

Technical considerations on the use of Granger causality in neuromonitoring

Neuromonitoring-derived indices play an important role in implementing personalised medicine for traumatic brain injury patients. A well-established example is the pressure reactivity index (PRx), calculated from spontaneous fluctuations of arterial blood pressure (ABP) and intracranial pressure (ICP). PRx assumes causal relationship between ABP and ICP but lacks the check for this assumption. Granger causality (GC) — a method of assessing causal interactions between time series data — is gaining popularity in neurosciences. In our work, we used ABP and ICP data recorded at the frequency of 100 Hz or higher from 235 traumatic brain injury patients. We focused on time domain GC. Analysis was first performed directly on high-resolution data, which included pulse waves. We showed that due to the measurement delay in high-resolution ABP data, GC analysis may erroneously indicate strong ICP→ABP causal relation. Subsequently, the data were downsampled to 0.1 Hz, effectively removing pulse and respiratory waves. We aimed to investigate how different ways of calculating GC influence results and which way should be recommended for ABP-ICP recordings. We considered aspects like selecting autoregressive model order and dealing with data non-stationarity. In addition, we generated simulated signals to investigate the influence of gaps and different procedures of missing data imputation on GC estimation. We showed that unlike methods which interpolate missing data, replacing missing data by white Gaussian noise did not increase the rate of false GC detection. Python source code used in this study is available at: https://github.com/m-m-placek/python-icmplus-granger-causality. Statement of significanceAssessing causality between time series data is of particular interest when neuromonitoring indices are derived from those time series and causal interaction between them is assumed. Causality assessment can improve reliability of such indices and open pathways for their safe clinical implementation. Granger Causality (GC) has recently been investigated in data collected from traumatic brain injury patients. However, there are two main issues related to applications suggested in these studies. Firstly, they considered GC for entire multi-day data recordings or for 24-h long episodes. There is interest in considering causal relationships in finer granularity, also in terms of their potential real-time applications at the bedside. Secondly, GC calculation requires selecting some parameters and there is no unique nor standardised way of doing that. Many papers often provide very brief description of data pre-processing and GC calculation. For this reason, it can be harder to reproduce and compare results derived from GC application. Different ways of obtaining GC may potentially lead to inconsistent results. Here, we attempted to explore possibility of time-varying GC of finer granularity and to provide general guidelines for application of GC to neurocritical care time series affected by periods of missing values.

Superior Fitting of Arterial Resistance and Compliance Parameters With Genetic Algorithms in Models of Dynamic Cerebral Autoregulation.

The capacity of discriminating between normal and impaired dynamic cerebral autoregulation (dCA), based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF), has considerable clinical relevance. This study aimed to quantify the separate contributions of vascular resistance and compliance as parameters that could reflect myogenic and metabolic mechanisms to dCA. Forty-five subjects were studied under normo and hypercapnic conditions induced by breathing a mixture of 5% carbon dioxide in air. Dynamic cerebrovascular resistance and compliance models with ABP as input and CBFV as output were fitted using Genetic Algorithms to identify parameter values for each subject, and respiratory condition. The efficiency of dCA was assessed from the model's generated CBFV response to an ABP step change, corresponding to an autoregulation index of 5.56 ± 1.57 in normocapnia and 2.38 ± 1.73 in hypercapnia, with an area under the ROC curve (AUC) of 0.9 between both conditions. Vascular compliance increased from 0.75 ± 0.7 ml/mmHg in normocapnia to 5.82 ± 12.0 ml/mmHg during hypercapnia, with an AUC of 0.88. Further work is needed to validate this approach in clinical applications where individualised model parameters could provide relevant diagnostic and prognostic information about dCA impairment.

Perspective on Cerebral Autoregulation Monitoring in Neonatal Cardiac Surgery Requiring Cardiopulmonary Bypass.

The autoregulation of cerebral blood flow protects against brain injury from transient fluctuations in arterial blood pressure. Impaired autoregulation may contribute to hypoperfusion injury in neonates and infants. Monitoring cerebral autoregulation in neonatal cardiac surgery as a guide for arterial blood pressure management may reduce neurodevelopmental morbidity. Cerebral autoregulation monitoring has been validated in animal models and in an adult trial autoregulation monitoring during bypass improved postoperative delirium scores. The nuances of pediatric cardiac disease and congenital heart surgery make simply applying adult trial findings to this unique population inappropriate. Therefore, dedicated pediatric clinical trials of cerebral autoregulation monitoring are indicated.

Optimal Cerebral Perfusion Pressure Based on Intracranial Pressure-Derived Indices of Cerebrovascular Reactivity: Which One Is Better for Outcome Prediction in Moderate/Severe Traumatic Brain Injury?

Intracranial pressure (ICP)-derived indices of cerebrovascular reactivity (e.g., PRx, PAx, and RAC) have been developed to improve understanding of brain status from available neuromonitoring variables. These indices are moving correlation coefficients between slow-wave vasogenic fluctuations in ICP and arterial blood pressure. In this retrospective analysis of neuromonitoring data from 200 patients admitted with moderate/severe traumatic brain injury (TBI), we evaluate the predictive value of CPPopt based on these ICP-derived indices of cerebrovascular reactivity. Valid CPPopt values were obtained in 92.3% (PRx), 86.7% (PAX), and 84.6% (RAC) of the monitoring periods, respectively. In multivariate logistic analysis, a baseline model that includes age, sex, and admission Glasgow Coma Score had an area under the receiver operating curve of 0.762 (P < 0.0001) for dichotomous outcome prediction (dead vs. good recovery). When adding time/dose of CPP below CPPopt, all multivariate models (based on PRx, PAx, and RAC) predicted the dichotomous outcome measure, but additional value of the prediction was only significantly added by the PRx-based calculations of time spent with CPP below CPPopt and dose of CPP below CPPopt.

COHmax: an algorithm to maximise coherence in estimates of dynamic cerebral autoregulation

Objective: The reliability of dynamic cerebral autoregulation (dCA) parameters, obtained with transfer function analysis (TFA) of spontaneous fluctuations in arterial blood pressure (BP), require statistically significant values of the coherence function. A new algorithm (COHmax) is proposed to increase values of coherence by means of the automated, selective removal of sub-segments of data. Approach: Healthy subjects were studied at baseline (normocapnia) and during 5% breathing of CO2 (hypercapnia). BP (Finapres), cerebral blood flow velocity (CBFV, transcranial Doppler), end-tidal CO2 (EtCO2, capnography) and heart rate (ECG) were recorded continuously during 5 min in each condition. TFA was performed with sub-segments of data of duration (SEGD) 100 s, 50 s or 25 s and the autoregulation index (ARI) was obtained from the CBFV response to a step change in BP. The area-under-the curve (AUC) was obtained from the receiver-operating characteristic (ROC) curve for the detection of changes in dCA resulting from hypercapnia. Main results: In 120 healthy subjects (69 male, age range 20–77 years), CO2 breathing was effective in changing mean EtCO2 and CBFV (p < 0.001). For SEGD = 100 s, ARI changed from 5.8 ± 1.4 (normocapnia) to 4.0 ± 1.7 (hypercapnia, p < 0.0001), with similar differences for SEGD = 50 s or 25 s. Depending on the value of SEGD, in normocapnia, 15.8% to 18.3% of ARI estimates were rejected due to poor coherence, with corresponding rates of 8.3% to 13.3% in hypercapnia. With increasing coherence, 36.4% to 63.2% of these could be recovered in normocapnia (p < 0.001) and 50.0% to 83.0% in hypercapnia (p < 0.005). For SEGD = 100 s, ROC AUC was not influenced by the algorithm, but it was superior to corresponding values for SEGD = 50 s or 25 s. Significance: COHmax has the potential to improve the yield of TFA estimates of dCA parameters, without introducing a bias or deterioration of their ability to detect impairment of autoregulation. Further studies are needed to assess the behaviour of the algorithm in patients with different cerebrovascular conditions.

Impaired Cerebrovascular Autoregulation in Large Vessel Occlusive Stroke after Successful Mechanical Thrombectomy: A Prospective Cohort Study

Introduction: Successful thrombectomy improves morbidity and mortality after stroke. The present prospective, observational cohort study investigated a potential correlation between the successful restoration of tissue perfusion by mechanical thrombectomy and intact cerebrovascular autoregulation (CA). Objective: Status of CA in patients with large vessel occlusive stroke after thrombectomy. Methods: After thrombectomy CA was measured using transcranial Doppler ultrasound. For this purpose a moving correlation index (Mxa) based on spontaneous arterial blood pressure fluctuations and corresponding cerebral blood flow velocity changes was calculated. CA impairment was defined by Mxa values more than .3. Results: Twenty patients with an acute occlusion of the middle cerebral artery or distal internal carotid artery were included. A successful recanalization of the occluded vessel via interventional thrombectomy was achieved in 10 of these patients (successful recanalization group), while in 10 patients mechanical recanalization failed or could not be applied (no recanalization group). Mean Mxa at stroke side was .58 ± .21 Table 2a in patients with successful intervention. At the unaffected hemisphere Mxa was .50 ± .20 Table 2a in successful recanalization group and .45 ± .24 Table 2b in no recanalization group without statistically significant differences. Based on the previously defined Mxa cut off more than .3, CA impairment was observable in all successful recanalized patients and in 8 of 10 patients with unsuccessful interventional treatment. Conclusions: These results suggest that brain perfusion may be affected due to impaired CA even after successful mechanical thrombectomy. Therefore, a tight blood pressure management is of great importance in post-thrombectomy stroke treatment to avoid cerebral hypo- and hyperperfusion.

The impact of physiological noise on hemodynamic-derived estimates of directed functional connectivity.

Measuring the strength of directed functional interactions between brain regions is fundamental to understand neural networks. Functional near-infrared spectroscopy (fNIRS) is a suitable method to map directed interactions between brain regions but is based on the neurovascular coupling. It, thus, relies on vasomotor reactivity and is potentially biased by non-neural physiological noise. To investigate the impact of physiological noise on fNIRS-based estimates of directed functional connectivity within the rostro-caudal hierarchical organization of the prefrontal cortex (PFC), we systematically assessed the effects of pathological perturbations of vasomotor reactivity and of externally triggered arterial blood pressure (aBP) fluctuations. Fifteen patients with unilateral stenosis of the internal carotid artery (ICA) underwent multi-channel fNIRS during rest and during metronomic breathing, inducing aBP oscillations at 0.1Hz. Comparisons between the healthy and pathological hemispheres served as quasi-experimental manipulation of the neurovascular system's capability for vasomotor reactivity. Comparisons between rest and breathing served as experimental manipulation of two different levels of physiological noise that were expected to differ between healthy and pathological hemispheres. In the hemisphere affected by ICA stenosis, the rostro-caudal hierarchical organization of the PFC was compromised reflecting the pathological effect on the vascular and neural level. Breathing-induced aBP oscillations biased the magnitude of directed interactions in the PFC, but could be adjusted using either the aBP time series (intra-individual approach) or the aBP-induced fNIRS signal variance (inter-individual approach). Multi-channel fNIRS, hence, provides a sound basis for analyses of directed functional connectivity as potential bias due to physiological noise can be effectively controlled for.

Associations between arterial stiffness and blood pressure fluctuations after spinal cord injury.

Cross-sectional. To examine the relationship between arterial stiffness and daily fluctuations in blood pressure (BP) owing to hypotensive events and autonomic dysreflexia (AD) in individuals with a T6 and above spinal cord injury (SCI). University-based laboratory in Vancouver, BC, Canada. Twenty-six individuals (73% male; 43 (11) years) with a chronic (> 1 year post SCI), traumatic, motor-complete SCI with a neurological level of injury of C4-T6 participated in this study. Arterial stiffness was assessed using carotid-to-femoral pulse wave velocity (cfPWV). BP was measured over a 24-hr period using ambulatory BP monitoring. AD was defined as an increase in systolic BP > 20 mmHg above baseline BP. Hypotensive events were defined as a decrease in systolic BP ≥ 20 mmHg and/or diastolic BP ≥ 10 mmHg below baseline. The severity and frequency of these events were quantified and Pearson and Spearman's correlations between them and cfPWV were performed. AD severity and frequency were not were correlated with cfPWV. For hypotensive events, both the frequency (r = 0.412, P = 0.04) and severity (Δsystolic BP; r = -0.425, P = 0.03) of these events were correlated with cfPWV. The combined total of AD and hypotensive events (9 (5) events/day) was also correlated with cfPWV (r = 0.480, P = 0.01). Hypotensive events, and the combined frequency of both hypo- and hypertensive events within a 24-hr period are associated with increased arterial stiffness in individuals with T6 and above SCI, suggesting BP instability may play a role in arterial stiffening post SCI.

Blunted sympathetic neurovascular transduction during normotensive pregnancy.

Normotensive pregnancy is associated with elevated sympathetic nervous system activity yet normal or reduced blood pressure. It represents a unique period of apparent healthy sympathetic hyperactivity. The present study models the blood pressure and heart rate (ECG R-R interval) responses to fluctuations in sympathetic nervous system activity aiming to understand neurocardiovascular transduction. The reported data clearly demonstrate that transduction of sympathetic nervous system signalling to systemic cardiovascular outcomes is reduced in normotensive pregnancy. These data are important for understanding how blood pressure regulation adapts during normotensive pregnancy and set the foundation for exploring similar mechanisms in hypertensive pregnancies. Previously, we described sympathetic nervous system hyperactivity yet decreased blood pressure responses to stress in normotensive pregnancy. To address the hypothesis that pregnant women have blunted neurocardiovascular transduction we assessed the relationship between spontaneous bursts of sympathetic nerve activity (SNA) and fluctuations in mean arterial blood pressure and R-R interval. Resting SNA, blood pressure and ECG were obtained in pregnant (third trimester, n=18) and non-pregnant (n=18) women matched for age and pre-/non-pregnant body mass index. Custom software modelled beat-by-beat pressure (photoplethysmography) and R-R interval in relation to sequences of SNA bursts and non-bursts (peroneal microneurography). Sequences were grouped by the number of bursts and non-bursts [singlets, doublets, triplets and quadruplet (four or more)] and mean blood pressure and R-R interval were tracked for 15 subsequent cardiac cycles. Similar sequences were overlaid and averaged. Peak mean pressure in relation to sequences of SNA was reduced in pregnant vs. non-pregnant women (doublets: 1.6±1.1mmHg vs. 3.6±3.1mmHg, P<0.05; triplets: 2.4±1.2mmHg vs. 3.4±2.1mmHg, P<0.05; quadruplets: 3.0±1.0mmHg vs. 5.5±3.7mmHg, P<0.05). The nadir R-R interval following burst sequences was also smaller in pregnant vs. non-pregnant women (singlets: -0.01±0.01s vs. -0.04±0.04s, P<0.05; doublets: -0.02±0.03s vs. -0.05±0.04s, P<0.05; triplets: -0.02±0.01s vs. -0.07±0.04s, P<0.05; quadruplets: -0.01±0.01s vs. -0.09±0.09s, P<0.05). There were no differences between groups in the mean arterial pressure and R-R interval responses to non-burst sequences. Our data clearly indicate blunted systemic neurocardiovascular transduction during normotensive pregnancy. We propose that blunted transduction is a positive adaptation protecting pregnant women from the cardiovascular consequences of sympathetic hyperactivity.