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Cerebral autoregulation maintains cerebral blood flow at a constant level when the mean arterial pressure is between approximately 50 and 150 mmHg (the plateau phase).
Source publication
Out of hospital cardiac arrest is the leading cause of death in industrialized countries. Recovery of hemodynamics does not necessarily lead to recovery of cerebral perfusion. The neurological injury induced by a circulatory arrest mainly determines the prognosis of patients after cardiac arrest and rates of survival with a favourable neurological...
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Objective
Recent studies have demonstrated the positive roles of remote ischemic conditioning (RIC) in patients with cerebrovascular diseases; however, the mechanisms remain unclear. This study aimed to explore the effect of serial RIC on dynamic cerebral autoregulation (dCA) and serum biomarkers associated with brain injury, both of which are rela...
Objectives
There is growing concern repetitive head contacts sustained by soccer players may lead to long-term health ramifications. Therefore, this preliminary investigation examined the impact an acute soccer heading bout has on dynamic cerebral autoregulation (dCA) metrics.
Methods
In this preliminary investigation, 40 successful soccer headers...
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In 1959, Niels Lassen illustrated the cerebral autoregulation curve in the classic review article entitled Cerebral Blood Flow and Oxygen Consumption in Man. This concept suggested a relatively broad mean arterial pressure range (~60–150 mmHg) wherein cerebral blood flow remains constant. However, the assumption that this wide cerebral autoregulati...
Purpose
We examined the effects of hypoxaemia on dynamic cerebral autoregulation (dCA) in lowlanders and Sherpa highlanders. We hypothesized that dCA in lowlanders would be reduced to a greater extent in the common carotid artery (CCA) compared to the internal carotid artery (ICA) during acute hypoxia at sea level and at high altitude, whereas Sher...
Citations
... Studies have highlighted that cerebral perfusion undergoes distinct phases following resuscitation, 12,13 illustrating the dynamic nature of perfusion changes and the critical importance of timing in perfusion imaging. PCABI features a series of circulatory changes resulting from global ischaemia and subsequent reperfusion which is often inhomogeneous and incomplete, leading to multifocal perfusion defects. ...
... Ca 2+ release causes the release of the glutamate resulting in neuronal excitotoxicity and further injury [78][79][80] Secondary brain injury occurs after restoration of CBF with return of spontaneous circulation (ROSC). Immediately after ROSC, CBF is characterized by early relative hyperemia followed by hypoperfusion resulting in endothelial dysfunction and microcirculatory abnormalities [78,80,81]. Additionally, cerebral autoregulation becomes significantly impaired post-arrest, leading to instability in CBF susceptible to fluctuations in MAP and CO 2 [82,83]. ...
Purpose of Review
Cardiac arrests constitute a leading cause of mortality in the adult population and cardiologists are often tasked with the management of patients following cardiac arrest either as a consultant or primary provider in the cardiac intensive care unit. Familiarity with evidence-based practice for post-cardiac arrest care is a requisite for optimizing outcomes in this highly morbid group. This review will highlight important concepts necessary to managing these patients.
Recent Findings
Emerging evidence has further elucidated optimal care of post-arrest patients including timing for routine coronary angiography, utility of therapeutic hypothermia, permissive hypercapnia, and empiric aspiration pneumonia treatment.
Summary
The complicated state of multi-organ failure following cardiac arrest needs to be carefully optimized by the clinician to prevent further neurologic injury and promote systemic recovery. Future studies should be aimed at understanding if these findings extend to specific patient populations, especially those at the highest risk for poor outcomes.
... Regarding hypoperfusion, the CPP and cerebrovascular resistance regulate cerebral blood flow (15). Although cerebral autoregulation maintains cerebral blood flow at a relatively constant level over a wide range of CPP (50 to 100 mmHg) (15,23), autoregulation of cerebrovascular resistance might be dysfunctional in certain circumstances [i.e., chronic hypertension (16,24), cardiac arrest (23), chronic heart failure (24), continuous flow LVAD (25)] that are frequently observed in this study population, and minor changes of CPP could injure the brain (19,20). During cerebral hypoperfusion in patients with post-LVAD RHF, deep brain structures that are supplied by the deep penetrating arteries and lack collateral flow or structures located at the junction supplied by both the middle and anterior cerebral arteries may be vulnerable to ischemic damage (19,20). ...
Background
Both stroke and right heart failure (RHF) are common and serious complications after left ventricular assist device (LVAD) implantation. The objective of this study was to evaluate relation between stroke and RHF early after LVAD implantation.
Methods
This is a retrospective observational cohort study. From January 2012 to December 2020, patients who underwent LVAD implantation in a single-center were enrolled. Patients with a non-dischargeable LVAD or without follow-up data were excluded. Early stroke was defined as a stroke event within 6 months after implantation. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definition was used for the diagnosis of RHF.
Results
A total of 70 patients underwent LVAD implantation. Sixty-seven patients (95.7%) were successfully discharged and 16 patients (22.9%) died during follow-up. 14 patients (20.0%) experienced a stroke within 6 months after implantation, and 0.28 stroke events per patient-year occurred during follow-up. Postoperative RHF was more common in the stroke group (64.3% vs. 23.2%, P=0.008) and the median time from implantation to RHF was 1 day. In the Cox multivariable analysis, postoperative RHF [hazard ratio (HR): 5.063; 95% confidence interval (CI): 1.682–15.245; P=0.004], and cerebral perfusion pressure (CPP) on postoperative day (POD) 1 (HR: 0.923; 95% CI: 0.858–0.992; P=0.030) were independent predictors for early stroke. A CPP of 62 mmHg (sensitivity, 71.4%; specificity, 59.3%) was the cutoff value for early stroke according to the receiver operating characteristic (ROC) analysis.
Conclusions
RHF after LVAD implantation may be a risk factor for early stroke. Prevention and management of postoperative RHF with adequate CPP could prevent early stroke after LVAD implantation.
... Resuscitated OHCA patients are heterogeneous, and cerebral dysregulation may manifest differently in each patient [38,43,44], therefore the influence of MAP on cerebral perfusion differs between patients and within each patient across different timepoints after ROSC. These patients may benefit from individualised, as opposed to static MAP targets, which may explain the neutral findings from our analysis of RCTs deploying static MAP targets. ...
... Resuscitated OHCA patients are heterogeneous, and cerebral dysregulation may manifest differently in each patient [38,43,44], therefore the influence of MAP on cerebral perfusion differs between patients and within each patient across different timepoints after ROSC. These patients may benefit from individualised, as opposed to static MAP targets, which may explain the neutral findings from our analysis of RCTs deploying static MAP targets. ...
Background:
With ideal mean arterial pressure (MAP) targets in resuscitated out-of-hospital cardiac arrest (OHCA) patients unknown, we performed a meta-analysis of randomised controlled trials (RCTs) to compare the effects of higher versus lower MAP targets.
Methods:
We searched four databases until 1 May 2023 for RCTs reporting the effects of higher MAP targets (>70 mmHg) in resuscitated OHCA patients and conducted random-effects meta-analyses. The primary outcome was mortality while secondary outcomes were neurological evaluations, arrhythmias, acute kidney injury, and durations of mechanical ventilation and ICU stay. We conducted inverse-variance weighted strata-level meta-regression against a proportion of non-survivors to assess differences between reported MAPs. We also conducted a trial sequential analysis of RCTs.
Results:
Four RCTs were included. Higher MAP was not associated with reduced mortality (OR: 1.09, 95%-CI: 0.84 to 1.42, p = 0.51), or improved neurological outcomes (OR: 0.99, 95%-CI: 0.77 to 1.27, p = 0.92). Such findings were consistent despite additional sensitivity analyses. Our robust variance strata-level meta-regression revealed no significant associations between mean MAP and the proportion of non-survivors (B: 0.029, 95%-CI: -0.023 to 0.081, p = 0.162), and trial sequential analysis revealed no meaningful survival benefit for higher MAPs.
Conclusions:
A higher MAP target was not significantly associated with improved mortality and neurological outcomes in resuscitated OHCA patients.
... Therefore, a rapid restoration of blood flow is very important for the normal activity of neurons. The return of spontaneous circulation does not naturally result in a recovery of cerebral perfusion, as cerebral perfusion failure after ischemia is well described in animal models with no reflow, hypoperfusion, and hyperperfusion [50]. Hyperperfusion is the result of a number of interrelated factors: impaired metabolism of vasodilators (nitric oxide-NO and prostacyclin), an increase in the level of vasoconstrictors (endothelin-1 and noradrenaline), a decrease in the production of anticoagulants by the endothelium with the formation of microthrombi, cerebral edema at the stage of ischemia because of hemostasis, and an increase in blood-brain barrier permeability. ...
Platinum nanoparticles (nPts) have neuroprotective/antioxidant properties, but the mechanisms of their action in cerebrovascular disease remain unclear. We investigated the brain bioavailability of nPts and their effects on brain damage, cerebral blood flow (CBF), and development of brain and systemic oxidative stress (OS) in a model of cerebral ischemia (hemorrhage + temporary bilateral common carotid artery occlusion, tBCAO) in rats. The nPts (0.04 g/L, 3 ± 1 nm diameter) were administered to rats (N = 19) intraperitoneally at the start of blood reperfusion. Measurement of CBF via laser Doppler flowmetry revealed that the nPts caused a rapid attenuation of postischemic hypoperfusion. The nPts attenuated the apoptosis of hippocampal neurons, the decrease in reduced aminothiols level in plasma, and the glutathione redox status in the brain, which were induced by tBCAO. The content of Pt in the brain was extremely low (≤1 ng/g). Thus, nPts, despite the extremely low brain bioavailability, can attenuate the development of brain OS, CBF dysregulation, and neuronal apoptosis. This may indicate that the neuroprotective effects of nPts are due to indirect mechanisms rather than direct activity in the brain tissue. Research on such mechanisms may offer a promising trend in the treatment of acute disorders of CBF.
... In addition, this evaluation may lead to a reliable determination of treatment effects, prognosis, and individualized treatments by establishing a new target population. Several studies have reported impaired CVAR post-CA 9,19 and some studies have assessed the association between CVAR and neurological outcome in HIBI. 16,20 The sample size in these studies was small and further validation is required. ...
This prospective observational single-center cohort study aimed to determine an association between cerebrovascular autoregulation (CVAR) and outcomes in hypoxic-ischemic brain injury post-cardiac arrest (CA), and assessed 100 consecutive post-CA patients in Japan between June 2017 and May 2020 who experienced a return of spontaneous circulation. Continuous monitoring was performed for 96 h to determine CVAR presence. A moving Pearson correlation coefficient was calculated from the mean arterial pressure and cerebral regional oxygen saturation. The association between CVAR and outcomes was evaluated using the Cox proportional hazard model; non-CVAR time percent was the time-dependent, age-adjusted covariate. The non-linear effect of target temperature management (TTM) was assessed using a restricted cubic spline. Of the 100 participants, CVAR was detected using the cerebral performance category (CPC) in all patients with a good neurological outcome (CPC 1-2) and in 65 patients (88%) with a poor outcome (CPC 3-5). Survival probability decreased significantly with increasing non-CVAR time percent. The TTM versus the non-TTM group had a significantly lower probability of a poor neurological outcome at 6 months with a non-CVAR time of 18%-37% (p < 0.05). Longer non-CVAR time may be associated with significantly increased mortality in hypoxic-ischemic brain injury post-CA.
... Until recently, it was assumed that under normal circumstances, autoregulation maintains a constant cerebral blood flow, and changes in mean blood pressure within a range of 50-150 mmHg have a minor influence on cerebral blood flow [209,210]. However, recent evidence suggests that autoregulation maintains cerebral blood flow within a smaller range above baseline MAP [16,211]. After cardiac arrest, the evidence is conflicting, with several studies showing that cerebral autoregulation is preserved after cardiac arrest [212,213], while other studies reported the absence of autoregulation [214]. ...
Cardiac arrest affects millions of people per year worldwide. Although advances in cardiopulmonary resuscitation and intensive care have improved outcomes over time, neurologic impairment and multiple organ dysfunction continue to be associated with a high mortality rate. The pathophysiologic mechanisms underlying the post-resuscitation disease are complex, and a coordinated, evidence-based approach to post-resuscitation care has significant potential to improve survival. Critical care management of patients resuscitated from cardiac arrest focuses on the identification and treatment of the underlying cause(s), hemodynamic and respiratory support, organ protection, and active temperature control. This review provides a state-of-the-art appraisal of critical care management of the post-cardiac arrest patient.
... During and immediately after cardiac arrest, impairment of cerebral oxygen delivery is not solely due to ischemia and shock; microvascular dysfunction caused by micro thrombi, cerebral va-soconstriction, blood-brain barrier disruption, and failure of autoregulation impair cerebral perfusion too (5,6). Microthrombi and endothelial swelling may narrow capillaries to an extent that impedes red blood cell flow and thus oxygen transport (7,8). ...
During and immediately after cardiac arrest, cerebral oxygen delivery is impaired mainly by microthrombi and cerebral vasoconstriction. This may narrow capillaries so much that it might impede the flow of red blood cells and thus oxygen transport. The aim of this proof-of-concept study was to evaluate the effect of M101, an extracellular hemoglobin-based oxygen carrier (Hemarina SA, Morlaix, France) derived from Arenicola marina, applied during cardiac arrest in a rodent model, on markers of brain inflammation, brain damage and regional cerebral oxygen saturation.27 Wistar rats subjected to 6 min of asystolic cardiac arrest were infused M101 (300 mg/kg) or placebo (NaCl 0.9%) concomitantly with start of cardiopulmonary resuscitation. Brain oxygenation and five biomarkers of inflammation and brain damage (from blood, cerebrospinal fluid, and homogenates from four brain regions) were measured 8 hours after return of spontaneous circulation. In these 21 different measurements, M101-treated animals were not significantly different from controls except for phospho-tau (p-tau) only in single cerebellum regions (p = 0.048; ANOVA of all brain regions: p = 0.004). Arterial blood pressure increased significantly only at 4-8 min after return of spontaneous circulation (p < 0.001) and acidosis decreased (p = 0.009).While M101 applied during cardiac arrest did not significantly change inflammation or brain oxygenation, the data suggest cerebral damage reduction due to hypoxic brain injury, measured by p-tau. Global burden of ischemia appeared reduced since acidosis was less severe. Whether post-cardiac arrest infusion of M101 improves brain oxygenation is unknown and needs to be investigated.
... The term DCA refers to the cerebral vasculature's capacity to respond rapidly to changes in systemic blood pressure by dilating and constricting arterioles, thereby maintaining appropriate cerebral blood flow to prevent ischemic brain injury from hypo-perfusion or intracranial hemorrhage (ICH) due to hyper-perfusion [117]. DCA is impaired in patients with acute brain diseases, including ischemic stroke [118,119], hypoxic brain injury from cardiac arrest [120,121], traumatic brain injury [122], subarachnoid hemorrhage [123], and ICH [124], and impaired DCA is associated with worse neurological outcomes [125,126]. Prior studies in animal models and humans have suggested that preeclampsia may be associated with impaired cerebral autoregulation [115,127]. ...
This dissertation develops uncertainty quantification methodologies for modeling, response analysis and optimization of diverse dynamical systems. Two distinct application platforms are considered pertaining to engineering dynamics and precision medicine.
First, the recently developed Wiener path integral (WPI) technique for determining, accurately and in a computationally efficient manner, the stochastic response of diverse dynamical systems is employed for solving a high-dimensional, nonlinear system of stochastic differential equations governing the dynamics of a representative model of electrostatically coupled micromechanical oscillators. Compared to alternative modeling and solution treatments in the literature, the current development exhibits the following novelties: a) typically adopted linear, or higher-order polynomial, approximations of the nonlinear electrostatic forces are circumvented; and b) stochastic modeling is employed, for the first time, by considering a random excitation component representing the effect of diverse noise sources on the system dynamics.
Further, the WPI technique is enhanced and extended based on a Bayesian compressive sampling (CS) treatment. Specifically, sparse expansions for the system response joint PDF are utilized. Next, exploiting the localization capabilities of the WPI technique for direct evaluation of specific PDF points leads to an underdetermined linear system of equations for the expansion coefficients. Furthermore, relying on a Bayesian CS solution formulation yields a posterior distribution for the expansion coefficient vector. In this regard, a significant advantage of the herein-developed methodology relates to the fact that the uncertainty of the response PDF estimates obtained by the WPI technique is quantified. Also, an adaptive scheme is proposed based on the quantified uncertainty of the estimates for the optimal selection of PDF sample points. This yields considerably fewer boundary value problems to be solved as part of the WPI technique, and thus, the associated computational cost is significantly reduced.
Second, modeling and analysis of the physiological mechanism of dynamic cerebral autoregulation (DCA) is pursued based on the concept of diffusion maps. Specifically, a state-space description of DCA dynamics is considered based on arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), and their time derivatives. Next, an eigenvalue analysis of the Markov matrix of a random walk on a graph over the dataset domain yields a low-dimensional representation of the intrinsic dynamics. Further dimension reduction is made possible by accounting only for the two most significant eigenvalues. The value of their ratio indicates whether the underlying system is governed by active or hypoactive dynamics, indicating healthy or impaired DCA function, respectively. The reliability of the technique is assessed by considering healthy individuals and patients with unilateral carotid artery stenosis or occlusion.
It is shown that the proposed ratio of eigenvalues can be used as a reliable and robust biomarker for assessing how active the intrinsic dynamics of the autoregulation is and for indicating healthy versus impaired DCA function. Further, an alternative joint time-frequency analysis methodology based on generalized harmonic wavelets is utilized for assessing DCA performance in patients with preeclampsia within one week postpartum, which is associated with an increased risk for postpartum maternal cerebrovascular complications. The results are compared with normotensive postpartum individuals and healthy non-pregnant female volunteers and suggest a faster, but less effective response of the cerebral autoregulatory mechanism in the first week postpartum, regardless of preeclampsia diagnosis.
