Constant Cerebral Blood Flow Research Articles

Cerebral Autoregulation: A Target for Improving Neurological Outcomes in Extracorporeal Life Support.

Despite improvements in survival after illnesses requiring extracorporeal life support, cerebral injury continues to hinder successful outcomes. Cerebral autoregulation (CA) is an innate protective mechanism that maintains constant cerebral blood flow in the face of varying systemic blood pressure. However, it is impaired in certain disease states and, potentially, following initiation of extracorporeal circulatory support. In this review, we first discuss patient-related factors pertaining to venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) and their potential role in CA impairment. Next, we examine factors intrinsic to ECMO that may affect CA, such as cannulation, changes in pulsatility, the inflammatory and adaptive immune response, intracranial hemorrhage, and ischemic stroke, in addition to ECMO management factors, such as oxygenation, ventilation, flow rates, and blood pressure management. We highlight potential mechanisms that lead to disruption of CA in both pediatric and adult populations, the challenges of measuring CA in these patients, and potential associations with neurological outcome. Altogether, we discuss individualized CA monitoring as a potential target for improving neurological outcomes in extracorporeal life support.

Associations Between Intracranial Pressure Extremes and Continuous Metrics of Cerebrovascular Pressure Reactivity in Acute Traumatic Neural Injury: A Scoping Review.

Cerebrovascular pressure reactivity plays a key role in maintaining constant cerebral blood flow. Unfortunately, this mechanism is often impaired in acute traumatic neural injury states, exposing the already injured brain to further pressure-passive insults. While there has been much work on the association between impaired cerebrovascular reactivity following moderate/severe traumatic brain injury (TBI) and worse long-term outcomes, there is yet to be a comprehensive review on the association between cerebrovascular pressure reactivity and intracranial pressure (ICP) extremes. Therefore, we conducted a systematic review of the literature for all studies presenting a quantifiable statistical association between a continuous measure of cerebrovascular pressure reactivity and ICP in a human TBI cohort. The methodology described in the Cochrane Handbook for Systematic Reviews was used. BIOSIS, Cochrane Library, EMBASE, Global Health, MEDLINE, and SCOPUS were all searched from their inceptions to March of 2023 for relevant articles. Full-length original works with a sample size of ≥10 patients with moderate/severe TBI were included in this review. Data were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 16 articles were included in this review. Studies varied in population characteristics and statistical tests used. Five studies looked at transcranial Doppler-based indices and 13 looked at ICP-based indices. All but two studies were able to present a statistically significant association between cerebrovascular pressure reactivity and ICP. Based on the findings of this review, impaired reactivity seems to be associated with elevated ICP and reduced ICP waveform complexity. This relationship may allow for the calculation of patient-specific ICP thresholds, past which cerebrovascular reactivity becomes persistently deranged. However, further work is required to better understand this relationship and improve algorithmic derivation of such individualized ICP thresholds.

The conducted vascular response as a mediator of hypercapnic cerebrovascular reactivity: A modelling study

It is well established that the cerebral blood flow (CBF) shows exquisite sensitivity to changes in the arterial blood partial pressure of CO2 (Pa,CO2), which is reflected by an index termed cerebrovascular reactivity. In response to elevations in Pa,CO2 (hypercapnia), the vessels of the cerebral microvasculature dilate, thereby decreasing the vascular resistance and increasing CBF. Due to the challenges of access, scale and complexity encountered when studying the microvasculature, however, the mechanisms behind cerebrovascular reactivity are not fully understood. Experiments have previously established that the cholinergic release of the Acetylcholine (ACh) neurotransmitter in the cortex is a prerequisite for the hypercapnic response. It is also known that ACh functions as an endothelial-dependent agonist, in which the local administration of ACh elicits local hyperpolarization in the vascular wall; this hyperpolarization signal is then propagated upstream the vascular network through the endothelial layer and is coupled to a vasodilatory response in the vascular smooth muscle (VSM) layer in what is known as the conducted vascular response (CVR). Finally, experimental data indicate that the hypercapnic response is more strongly correlated with the CO2 levels in the tissue than in the arterioles. Accordingly, we hypothesize that the CVR, evoked by increases in local tissue CO2 levels and a subsequent local release of ACh, is responsible for the CBF increase observed in response to elevations in Pa,CO2. By constructing physiologically grounded dynamic models of CBF and control in the cerebral vasculature, ones that integrate the available knowledge and experimental data, we build a new model of the series of signalling events and pathways underpinning the hypercapnic response, and use the model to provide compelling evidence that corroborates the aforementioned hypothesis. If the CVR indeed acts as a mediator of the hypercapnic response, the proposed mechanism would provide an important addition to our understanding of the repertoire of metabolic feedback mechanisms possessed by the brain and would motivate further in-vivo investigation. We also model the interaction of the hypercapnic response with dynamic cerebral autoregulation (dCA), the collection of mechanisms that the brain possesses to maintain near constant CBF despite perturbations in pressure, and show how the dCA mechanisms, which otherwise tend to be overlooked when analysing experimental results of cerebrovascular reactivity, could play a significant role in shaping the CBF response to elevations in Pa,CO2. Such in-silico models can be used in tandem with in-vivo experiments to expand our understanding of cerebrovascular diseases, which continue to be among the leading causes of morbidity and mortality in humans.

Conductivity reactivity index for monitoring of cerebrovascular autoregulation in early cerebral ischemic rabbits

BackgroundCerebrovascular autoregulation (CVAR) is the mechanism that maintains constant cerebral blood flow by adjusting the caliber of the cerebral vessels. It is important to have an effective, contactless way to monitor and assess CVAR in patients with ischemia.MethodsThe adjustment of cerebral blood flow leads to changes in the conductivity of the whole brain. Here, whole-brain conductivity measured by the magnetic induction phase shift method is a valuable alternative to cerebral blood volume for non-contact assessment of CVAR. Therefore, we proposed the correlation coefficient between spontaneous slow oscillations in arterial blood pressure and the corresponding magnetic induction phase shift as a novel index called the conductivity reactivity index (CRx). In comparison with the intracranial pressure reactivity index (PRx), the feasibility of the conductivity reactivity index to assess CVAR in the early phase of cerebral ischemia has been preliminarily confirmed in animal experiments.ResultsThere was a significant difference in the CRx between the cerebral ischemia group and the control group (p = 0.002). At the same time, there was a significant negative correlation between the CRx and the PRx (r = − 0.642, p = 0.002) after 40 min after ischemia. The Bland–Altman consistency analysis showed that the two indices were linearly related, with a minimal difference and high consistency in the early ischemic period. The sensitivity and specificity of CRx for cerebral ischemia identification were 75% and 20%, respectively, and the area under the ROC curve of CRx was 0.835 (SE = 0.084).ConclusionThe animal experimental results preliminarily demonstrated that the CRx can be used to monitor CVAR and identify CVAR injury in early ischemic conditions. The CRx has the potential to be used for contactless, global, bedside, and real-time assessment of CVAR of patients with ischemic stroke.

Non-Invasive Mapping of Cerebral Autoregulation Using Near-Infrared Spectroscopy: A Study Protocol.

The ability of cerebral vessels to maintain a fairly constant cerebral blood flow is referred to as cerebral autoregulation (CA). Using near-infrared spectroscopy (NIRS) paired with arterial blood pressure (ABP) monitoring, continuous CA can be assessed non-invasively. Recent advances in NIRS technology can help improve the understanding of continuously assessed CA in humans with high spatial and temporal resolutions. We describe a study protocol for creating a new wearable and portable imaging system that derives CA maps of the entire brain with high sampling rates at each point. The first objective is to evaluate the CA mapping system's performance during various perturbations using a block-trial design in 50 healthy volunteers. The second objective is to explore the impact of age and sex on regional disparities in CA using static recording and perturbation testing in 200 healthy volunteers. Using entirely non-invasive NIRS and ABP systems, we hope to prove the feasibility of deriving CA maps of the entire brain with high spatial and temporal resolutions. The development of this imaging system could potentially revolutionize the way we monitor brain physiology in humans since it would allow for an entirely non-invasive continuous assessment of regional differences in CA and improve our understanding of the impact of the aging process on cerebral vessel function.

Tale of Two Cities: narrative review of oxygen.

The human brain contributes 2% of the body weight yet receives 15% of cardiac output and demands a constant supply of oxygen (O 2) and nutrients to meet its metabolic needs. Cerebral autoregulation is responsible for maintaining a constant cerebral blood flow that provides the supply of oxygen and maintains the energy storage capacity. We selected oxygen administration-related studies published between 1975-2021 that included meta-analysis, original research, commentaries, editorial, and review articles. In the present narrative review, several important aspects of the oxygen effects on brain tissues and cerebral autoregulation are discussed, as well the role of exogenous O 2 administration in patients with chronic ischemic cerebrovascular disease: We aimed to revisit the utility of O 2 administration in pathophysiological situations whether or not being advantageous. Indeed, a compelling clinical and experimental body of evidence questions the utility of routine oxygen administration in acute and post-recovery brain ischemia, as evident by studies in neurophysiology imaging. While O 2 is still part of common clinical practice, it remains unclear whether its routine use is safe.

Tale of Two Cities: narrative review of oxygen

The human brain contributes 2% of the body weight yet receives 15% of cardiac output and demands a constant supply of oxygen (O2) and nutrients to meet its metabolic needs. Cerebral autoregulation is responsible for maintaining a constant cerebral blood flow that provides the supply of oxygen and maintains the energy storage capacity. We selected oxygen administration-related studies published between 1975–2021 that included meta-analysis, original research, commentaries, editorial, and review articles. In the present narrative review, several important aspects of the oxygen effects on brain tissues and cerebral autoregulation are discussed, as well the role of exogenous O2 administration in patients with chronic ischemic cerebrovascular disease: We aimed to revisit the utility of O2 administration in pathophysiological situations whether or not being advantageous. Indeed, a compelling clinical and experimental body of evidence questions the utility of routine oxygen administration in acute and post-recovery brain ischemia, as evident by studies in neurophysiology imaging. While O2 is still part of common clinical practice, it remains unclear whether its routine use is safe.

Non-Invasive and Minimally-Invasive Cerebral Autoregulation Assessment: A Narrative Review of Techniques and Implications for Clinical Research.

The process of cerebral vessels regulating constant cerebral blood flow over a wide range of systemic arterial pressures is termed cerebral autoregulation (CA). Static and dynamic autoregulation are two types of CA measurement techniques, with the main difference between these measures relating to the time scale used. Static autoregulation looks at the long-term change in blood pressures, while dynamic autoregulation looks at the immediate change. Techniques that provide regularly updating measures are referred to as continuous, whereas intermittent techniques take a single at point in time. However, a technique being continuous or intermittent is not implied by if the technique measures autoregulation statically or dynamically. This narrative review outlines technical aspects of non-invasive and minimally-invasive modalities along with providing details on the non-invasive and minimally-invasive measurement techniques used for CA assessment. These non-invasive techniques include neuroimaging methods, transcranial Doppler, and near-infrared spectroscopy while the minimally-invasive techniques include positron emission tomography along with magnetic resonance imaging and radiography methods. Further, the advantages and limitations are discussed along with how these methods are used to assess CA. At the end, the clinical considerations regarding these various techniques are highlighted.

Impact of Cerebral Autoregulation Monitoring in Cerebrovascular Disease: A Systematic Review.

Cerebral autoregulation (CA) prevents brain injury by maintaining a relatively constant cerebral blood flow despite fluctuations in cerebral perfusion pressure. This process is disrupted consequent to various neurologic pathologic processes, which may result in worsening neurologic outcomes. Herein, we aim to highlight evidence describing CA changes and the impact of CA monitoring in patients with cerebrovascular disease, including ischemic stroke, intracerebral hemorrhage (ICH), and aneurysmal subarachnoid hemorrhage (aSAH). The study was preformed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. English language publications were identified through a systematic literature conducted in Ovid Medline, PubMed, and Embase databases. The search spanned the dates of each database's inception through January 2021. We selected case-control studies, cohort observational studies, and randomized clinical trials for adult patients (≥ 18years) who were monitored with continuous metrics using transcranial Doppler, near-infrared spectroscopy, and intracranial pressure monitors. Of 2799 records screened, 48 studies met the inclusion criteria. There were 23 studies on ischemic stroke, 18 studies on aSAH, 5 studies on ICH, and 2 studies on systemic hypertension. CA impairment was reported after ischemic stroke but generally improved after tissue plasminogen activator administration and successful mechanical thrombectomy. Persistent impairment in CA was associated with hemorrhagic transformation, malignant cerebral edema, and need for hemicraniectomy. Studies that investigated large ICHs described bilateral CA impairment up to 12days from the ictus, especially in the presence of small vessel disease. In aSAH, impairment of CA was associated with angiographic vasospasm, delayed cerebral ischemia, and poor functional outcomes at 6months. This systematic review highlights the available evidence for CA disruption during cerebrovascular diseases and its possible association with long-term neurological outcome. CA may be disrupted even before acute stroke in patients with untreated chronic hypertension. Monitoring CA may help in establishing individualized management targets in patients with cerebrovascular disease.

Impaired Cerebral Autoregulation After Subarachnoid Hemorrhage: A Quantitative Assessment Using a Mouse Model.

Subarachnoid hemorrhage (SAH) is a common form of hemorrhagic stroke associated with high rates of mortality and severe disability. SAH patients often develop severe neurological deficits days after ictus, events attributed to a phenomenon referred to as delayed cerebral ischemia (DCI). Recent studies indicate that SAH-induced DCI results from a multitude of cerebral circulatory disturbances including cerebral autoregulation malfunction. Cerebral autoregulation incorporates the influence of blood pressure (BP) on arterial diameter in the homeostatic regulation of cerebral blood flow (CBF), which is necessary for maintaining constant brain perfusion during physiological swings in systemic BP. In this study, we quantitatively examined the impact of SAH on cerebral autoregulation using a mouse endovascular perforation model and a newly developed approach combining absolute and relative CBF measurements. This method enables a direct quantitative comparison of cerebral autoregulation between individual animals (e.g., SAH vs. control or sham-operated mice), which cannot be done solely using relative CBF changes by laser Doppler flowmetry. Here, absolute CBF was measured via injection of fluorescent microspheres at a baseline BP. In separate groups of animals, in vivo laser Doppler flowmetry was used to measure relative CBF changes over a range of BP using phlebotomy and the pressor phenylephrine to lower and raise BP, respectively. Absolute CBF measurements from microspheres were then used to calibrate laser Doppler measurements to calculate the relationship between CBF and BP, i.e., “cerebral autoregulation curves.” Un-operated and sham-operated groups exhibited similar cerebral autoregulatory curves, showing comparable levels of relatively constant CBF over a range of BP from ~80 mmHg to ~130 mmHg. In contrast, SAH animals exhibited a narrower autoregulatory range of BP, which was primarily due to a decrease in the upper limit of BP whereby cerebral autoregulation was maintained. Importantly, SAH animals also exhibited a marked decrease in CBF throughout the entire range of BP. In sum, this study provides evidence of the dramatic reduction in cortical CBF and the diminished range of autoregulation after SAH. Furthermore, this novel methodology should pave the way for future studies examining pathological mechanisms and/or therapeutic strategies targeting impaired cerebral autoregulation, a pathology common to many cardiovascular and cerebrovascular disorders.

Xiaoxuming Decoction Regulates Vascular Function by Modulating G Protein-Coupled Receptors: A Molecular Docking Study.

Xiaoxuming decoction (XXMD) is a traditional Chinese herbal medicine (CHM) that is used for the treatment of stroke in China. Stroke injury damages the cerebral vasculature and disrupts the autoregulation of vasoconstriction and vasodilatation, which is crucial for maintaining constant cerebral blood flow (CBF). It has been reported that XXMD exerts a positive effect on cerebral circulation in animal models of stroke. However, the mechanisms underlying the regulatory effect of XXMD on vascular tone, and the interactions among the multiple components of XXMD, remain unclear. In this study, XXMD was found to induce relaxation of the basilar artery rings of rats precontracted by 5-hydroxytryptamine (5-HT) in vitro, in a dose-dependent manner. The modulation of vascular tone and the process of cerebral ischemia are mediated via the interactions between G protein-coupled receptors (GPCRs) and their ligands, including 5-HT, angiotensin II (Ang II), and urotensin II (UII). Thus, the potential synergistic effects of the different components of XXMD on the regulation of vasoconstriction and vasodilation were further investigated by molecular docking based on network pharmacology. We constructed and analyzed a database comprising 963 compounds of XXMD and studied the interactions between five vascular GPCRs (5-HT1A receptor (5-HT1AR), 5-HT1B receptor (5-HT1BR), Ang II type 1 receptor (AT1R), beta 2-adrenergic receptor (β2-AR), and UII receptor (UTR)) and the various herbal constituents of XXMD using molecular docking. By constructing and analyzing the compound-target networks of XXMD, we found that Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, and Paeoniae Radix Alba were the three major herbs that contained a large number of compounds with high docking scores. We additionally observed that several constituents of XXMD, including gallotannin, liquiritin apioside, nariutin, 1,2,3,4,6-pentagalloylglucose, folic acid, and ginsenoside Rb1, targeted multiple vascular GPCRs. Moreover, the interactions between the components of XXMD and the targets related to vascular tone constituted the comprehensive cerebrovascular regulatory function of XXMD and provided a material basis of the vasoregulatory function of XXMD. The study reports the contributions of various components of XXMD to the regulatory effects on vascular tone and provides scientific evidence for the multicomponent and multitargeting characteristics of XXMD.

Investigating the role of pericytes in cerebral autoregulation: a modeling study

The brain’s inability to store nutrients for more than a few seconds makes it one of the most tightly regulated systems in the body. Driven by metabolic demand, cerebral autoregulation (CA) ensures a constant cerebral blood flow (CBF) over a ±50% change in arterial blood pressure (ABP) from baseline. Recent evidence suggests that pericytes, contractile cells in the capillary bed, play a previously-ignored regulatory role. To elucidate the CA phenomenon, the role of oxygen metabolism, pericyte activity and neural signaling in CBF modulation were quantified. Driven by nutrient metabolism in the tissue and pressure sensitivity in the vasculature, the model introduced here successfully replicates CA. To highlight the role of different vessel sizes, vessels with a diameter above 1 mm were represented using a lumped parameter model while the microvasculature was illustrated as a branching tree network model. This novel approach elucidated the relationship between the microvasculature’s nutrient supply and arterial regulation. Capillary responses to local increases in neuronal activity were experimentally determined, showing that pericytes can increase the diameter of the adjacent vessel by 2.5% in approximately 1 s. Their response was quantified and included in the computational model as an active component of the capillary bed. To compare the efficacy model presented here to existing ones, four feedback mechanisms were tested. To simulate dynamic CBF regulation a 10% increase in ABP was imposed. This resulted in a 23.79%–34.33% peak increase in CBF, depending on the nature of the feedback mechanism of the model. The four feedback mechanisms that were studied significantly differ in the response time, ultimately highlighting that capillaries play a fundamental role in the rapid regulation of CBF. Conclusively, this study indicates that while pericytes do not greatly alter the peak CBF change, they play a fundamental role in the speed of regulation.

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.

Spaceflight not an eye-popping experience for astronauts.

Spaceflight not an eye-popping experience for astronauts.

Aerobic Exercise Acutely Improves Dynamic Cerebral Autoregulation During Brain Activation

PURPOSE: Cognitive function is temporarily improved by acute aerobic exercise, especially clinical high-intensity interval exercise (cHIIE; four 4 min bouts of high-intensity exercise) (Tsukamoto et al. 2016). Meanwhile, dynamic cerebral autoregulation (dCA) is an important cerebrovascular mechanism to maintain relatively constant cerebral blood flow (CBF) against the rapid fluctuations in perfusion pressure, but it is impaired during cognitive tasks (causing brain activation) due to cerebral vasodilation (Ogoh et al. 2018). Although it has been demonstrated that dCA is not changed by aerobic exercise (Tsukamoto et al. 2019), which improves cognitive function (Tsukamoto et al. 2016), the impact of aerobic exercise on the brain activation-induced dCA impairment remains unclear. The purpose of the present study was to investigate the changes in dCA during a cognitive task prior to following different types of aerobic exercise. METHODS: Nine healthy male subjects performed three trials in a randomized crossover order; moderate-intensity continuous exercise (for 40 min), low-volume HIIE (lvHIIE; ten 1 min bouts of high-intensity exercise), and cHIIE protocols. The participants performed a 5 min color-word Stroop task (cognitive task) before, immediately after, and 30 min after each exercise bout. Middle cerebral artery blood flow velocity (Transcranial doppler ultrasonography) and arterial pressure (Finger photosplethysmography) were continuously measured to determine dCA using transfer function analysis, and dCA was estimated at rest and during each cognitive task. RESULTS: Before exercise, transfer function phase in the very low-frequency (VLF) was decreased during cognitive task compared to the resting measurement (P < 0.01), indicating that there was brain activation-induced dCA impairment. However, VLF phase during the cognitive task immediately after exercise was higher than before (P < 0.01) and 30 min (P < 0.01) after exercise regardless of exercise protocol, indicating that dCA impairment during the cognitive task was blunted immediately after exercise. CONCLUSIONS: The brain activation-induced dCA impairment is attenuated immediately after exercise. This result implies that aerobic exercise improves dynamic CBF regulation in response to brain activation during a cognitive task.

Impaired cerebral blood flow regulation in chronic traumatic brain injury

Baroreflex sensitivity (BRS) and cerebral autoregulation (CA) play an important role in maintaining constant cerebral blood flow (CBF) during systemic changes in blood pressure (BP). Impaired BRS and CA have been reported in acute traumatic brain injury (TBI) which may also contribute to secondary injury and poorer recovery after acute TBI; however, their status during chronic stages remains elusive. Thus, the goal of this study is to determine whether cardiac BRS and dynamic CA (dCA) were impaired during the chronic stage in patients with single TBI and persistent neurological symptoms. Twenty-two subjects with blunt head TBI ≥ 6 months prior to the study (13 mild and 9 moderate to severe TBI) and persistent symptoms on Rivermead Post-Concussion Symptoms Questionnaire at enrollment were compared to 22 age/sex/fitness level-matched healthy control subjects. Beat-to-beat changes in heart rate, BP, and CBF velocity were measured at rest and during a repeated sit-stand maneuver. Hemodynamic variability, dCA, and cardiac BRS were calculated using spectral and transfer function analyses. We found dCA phase in low frequency (LF) range of 0.07–0.20 Hz was lower in subjects with TBI than in control subjects (0.51 ± 0.19 vs. 0.63 ± 0.26, p = 0.043) during the resting condition. Among subjects with TBI, the lower dCA phase in LF was correlated with poorer performance on measures of cognitive function (all p < 0.05). These findings suggested that subjects with chronic TBI showed impaired dCA which may contribute to persistent cognitive impairment. Cerebrovascular measures may provide a physiological measure to evaluate interventions for chronic TBI and accompanying functional deficits.

Cerebral Hemodynamics Are Not Affected by the Size of the Patent Ductus Arteriosus

Introduction: Although patent ductus arteriosus (PDA) has been implicated to play a role in the development of cerebral ischemia and intraventricular hemorrhage (IVH) through a cerebral steal phenomenon, there is conflicting data on the impact of PDA size on cerebral blood flow (CBF). Cerebral autoregulation is the brain’s innate protective mechanism to maintain constant CBF despite changes in blood pressure, and it is unclear if it is influenced by PDA hemodynamics. Objective: To delineate the relationship between PDA size and CBF velocity (CBFv) in premature infants. Methods: 113 premature infants born at 23–29 weeks’ gestation had echocardiograms performed during the first week after birth to evaluate for PDA. The infants were divided into 3 groups according to PDA size: none-to-small, moderate, or large. All infants had continuous recordings of umbilical artery blood pressure (ABP) and CBFv during the first week after birth. Critical closing pressure (CrCP) was calculated from ABP and CBFv tracings. Diastolic closing margin (DCM), defined as diastolic blood pressure minus CrCP, was calculated as a marker for the risk of developing IVH. Results: Infants with a large PDA (n = 16) had the lowest ABP across all phases of the cardiac cycle (systole [p = 0.003], mean [p = 0.005], and diastole [p = 0.012]) compared to infants with a moderate (n = 19) or none-to-small PDA (n = 78). Despite blood pressure being different, systolic, mean, and diastolic CBFv were not different across groups. Cerebral autoregulation, as measured during systole, was intact regardless of the PDA size. CrCP and DCM were also not different across groups. Conclusions: In this cohort, CBFv and cerebral autoregulation during systole were not influenced by PDA size. Intact cerebral autoregulation may play a role in maintaining CBFv regardless of PDA size and differences in ABP.

Epidural electrical stimulation and hemodynamic control after spinal cord injury

Spinal cord injury impairs cerebral autoregulation (i.e., the buffering of changes in blood pressure in an effort to maintain cerebral blood flow constant) and baroreflex sensitivity (i.e., the appropriate heart rate responses to changes in blood pressure), due in part to the disruption of supraspinal sympathetic control of circuits below the level of injury. This impairment is almost certainly associated with the greater risk of cerebrovascular and heart disease observed in this population.We have previously shown in people with spinal cord injury that epidural electrical stimulation of the spinal cord below the level of injury (eSTIM) activates disconnected sympathetic circuits. Furthermore, long‐term daily application of eSTIM can in some cases lead to plasticity that restores function, even when eSTIM is off. It is not clear if eSTIM activation of sympathetic circuits restores cerebral autoregulation and baroreflex function after spinal cord injury, or if functionally‐relevant plasticity occurs after long‐term application of eSTIM.Here, we show that activating eSTIM immediately improves cerebral autoregulation and baroreflex sensitivity. These positive immediate effects were repeatable over several months. Long‐term daily eSTIM for at least 12 weeks did not affect cerebral autoregulation or baroreflex function when stimulation was off, indicating that functionally‐relevant plasticity did not occur. In conclusion, immediate application of eSTIM may be a viable therapy for improving hemodynamic control after spinal cord injury.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Libin Cardiovascular Institute of Alberta, Hotchkiss Brain Institute, Compute Canada.Cerebral autoregulation was consistently improved with the activation of eSTIM as indicated by increased phase lag between blood pressure and cerebral blood flow. Cardiovagal baroreflex function was also improved as indicated by more rapid heart rate responses to changes in blood pressure. **indicates significant difference (p&lt;0.005)Figure 1

75 Is Cerebral Autoregulation Altered in Ageing? A Review

Abstract Introduction Cerebral autoregulation (CA) ensures constant cerebral blood flow (CBF) in the face of blood pressure (BP) disturbances. While CA impairment is often implicated in the aetiology of age-related disorders e.g. falls, syncope, and brain ageing, there is conflicting evidence on the effect of normal or healthy ageing on cerebral autoregulation. Here we present results of a review investigating the effect of ageing on CA. Methods A search was performed in Pubmed using the search terms “cerebral autoregulation” AND (“ageing” OR “age” OR “older” OR “elderly”). Studies were included if they were human studies in English assessing CA in healthy volunteers (free from disease) in which the effect of ageing on CAR was studied. Exclusion criteria included non-human studies, diseased cohorts and studies not measuring CA. Results 26 studies (n=1326 total participants, age range 12-88) meeting the inclusion/exclusion criteria were identified. Significant heterogeneity was noted in applied methodologies with 88% of studies using static and 53% using dynamic protocols to measure CA. Transcranial Doppler (88%) and Near Infrared Spectroscopy (NIRS) (11%) were the most commonly used. Transfer function analysis (TFA) (38%), the Autoregulatory Index (ARI) (15%), and wavelet analysis (11%) were used to derive CA metric. The majority of studies suggested that CA is preserved (n=15) with ageing. However, a smaller number of studies (n=7) noted that CA is impaired or altered with ageing. Conclusions There is a paucity of literature examining the relationship between CA and chronological ageing, with 60 per cent of studies reviewed suggesting that CA is preserved. Current hypotheses suggest that preservation of CA with ageing serves as a ‘reserve’ to compensate for impairment of other systems. Future work should investigate the role of impaired CA as potential biomarker of biological ageing.

Aging influences cerebrovascular function via BK channel in a sex‐specific manner

The myogenic response of middle cerebral arteries (MCA) protects the brain by altering the diameter in response to lumen pressure to maintain constant cerebral blood flow. Large conductance potassium (BK) channels are known to regulate the myogenic response. However, it is not clear how aging will influence the myogenic response via altering BK channel function in males and females. Here, using vascular reactivity, patch‐clamp and biochemical methods, we found that age‐associated changes in BK channel subunit expression and function alter myogenic response in a sex‐specific manner. Aging exaggerated the myogenic response of MCA of females but did not change the myogenic response in males. Aging abolished differences in myogenic tone of MCA (MT as determined from active and passive diameters) in males and females. Aging, while decreased wall to lumen ratio in females, it increased in males revealing a sex‐specific difference in MCA remodeling. Aging while decreased total K channel and BK channel currents in vascular smooth muscle cells (VSMCs) isolated from female vessels, it did not affect males. Spontaneous transient outward currents (STOC) that represent BK function are also decreased with aging in both males and females. However, the magnitude of the decrease in STOC amplitude and frequency is much greater in aged females than aged males. While aging increased BKα subunit, it decreased β1 subunit protein in cerebral vessels of both males and females. Age‐associated increase in BKα subunit is similar between males and females. However, there is a greater and significant reduction of BKβ1 subunit protein in aged females than aged males. Activation of BKα and β1 subunits either individually or both failed to decrease MT of MCA isolated from aged males and females at physiological lumen pressures. Besides, aging diminished acute estradiol (17βE)‐mediated decrease in MT either alone or combined with BKβ1 agonist in females. However, this combination significantly decreased MT in ovariectomy females that are chronically supplemented with 17βE via increasing BKβ1 protein content. Overall our results suggest that age‐associated changes in cerebral vascular structure and function and that of BK channel subunit expression and function are sex‐specific. Chronic supplementation of 17βE increases BKβ1 protein content, and its activation by agonist combined with acute 17βE attenuates MT in aged females.Support or Funding InformationSupported by AHA SDG (13SDG14000006) and IRSP from UMMC to Mallikarjuna R. Pabbidi.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.