Hemodynamic variability and cerebrovascular control after transient cerebral ischemia

We investigated if hemodynamic variability, cerebral blood flow (CBF) regulation, and their interrelationships differ between patients with transient ischemic attack (TIA) and controls. We recorded blood pressure (BP) and bilateral middle cerebral artery flow velocity (MCAv) in a cohort of TIA patients (n = 17), and age?matched controls (n = 15). Spontaneous fluctuations in BP and MCAv were characterized by spectral power analysis, and CBF regulation was assessed by wavelet phase synchronization analysis in the very low? (0.02–0.07 Hz), low? (0.07–0.20 Hz), and high?frequency (0.20–0.40 Hz) ranges. Furthermore, cerebrovascular CO2 reactivity was assessed as a second metric of CBF regulation by inducing hypercapnia with 8% CO2 inhalation followed by hyperventilation driven hypocapnia. We found that TIA was associated with higher BP power (group effect, P < 0.05), but not MCAv power (P = 0.11). CBF regulation (assessed by wavelet phase synchronization and CO2 reactivity) was intact in patients (all P ? 0.075) across both hemispheres (all P ? 0.51). Pooled data (controls and affected hemisphere of patients) showed that BP and MCAv power were positively correlated at all frequency ranges (R2 = 0.20–0.80, all P < 0.01). Furthermore, LF phase synchronization index was a significant determinant of MCAv power (P < 0.05), while VLF and HF phase synchronization index, and TIA were not (all P ? 0.50). These results indicate that CBF stability and control is maintained in TIA patients, but BPV is markedly elevated. BPV attenuation may be an important therapeutic strategy for enhancing secondary stroke prevention in patients who suffer a TIA

Effects of arterial blood gas levels on cerebral blood flow and oxygen transport

Near Infra-Red Spectroscopy (NIRS) is a non-invasive technique which can be used to investigate cerebral haemodynamics and oxygenation with high temporal resolution. When combined with measures of Cerebral Blood Flow (CBF), it has the potential to provide information about oxygen delivery, utilization and metabolism. However, the interpretation of experimental results is complex. Measured NIRS signals reflect both scalp and cerebral haemodynamics and are influenced by many factors. The relationship between Arterial Blood Pressure (ABP) and CBF has been widely investigated and it central to cerebral autoregulation. Changes in arterial blood gas levels have a significant effect on ABP and CBF and these relationships have been quantified previously. The relationship between ABP and NIRS signals, however, has not been fully characterized. In this paper, we thus investigate the influence of changes in arterial blood gas levels both experimentally and theoretically, using an extended mathematical model of cerebral blood flow and metabolism, in terms of the phase angle at 0.1 Hz. The autoregulation response is found to be strongly dependent upon the carbon dioxide (CO2) partial pressure but much less so upon changes in arterial oxygen saturation (SaO2). The results for phase angle sensitivity to CO2 show good agreement between experimental and theory, but a poorer agreement is found for the sensitivity to SaO2

Wavelet pressure reactivity index: a validation study.

KEY POINTS: The brain is vulnerable to damage from too little or too much blood flow. A physiological mechanism termed cerebral autoregulation (CA) exists to maintain stable blood flow even if cerebral perfusion pressure (CPP) is changing. A robust method for assessing CA is not yet available. There are still some problems with the traditional measure, the pressure reactivity index (PRx). We introduce a new method, the wavelet transform method (wPRx), to assess CA using data from two sets of controlled hypotension experiments in piglets: one set had artificially manipulated arterial blood pressure (ABP) oscillations; the other group were spontaneous ABP waves. A significant linear relationship was found between wPRx and PRx in both groups, with wPRx providing a more stable result for the spontaneous waves. Although both methods showed similar accuracy in distinguishing intact and impaired CA, it seems that wPRx tends to perform better than PRx, although not significantly so. ABSTRACT: We present a novel method to monitor cerebral autoregulation (CA) using the wavelet transform (WT). The new method is validated against the pressure reactivity index (PRx) in two piglet experiments with controlled hypotension. The first experiment (n = 12) had controlled haemorrhage with artificial stationary arterial blood pressure (ABP) and intracranial pressure (ICP) oscillations induced by sinusoidal slow changes in positive end-expiratory pressure ('PEEP group'). The second experiment (n = 17) had venous balloon inflation during spontaneous, non-stationary ABP and ICP oscillations ('non-PEEP group'). The wavelet transform phase shift (WTP) between ABP and ICP was calculated in the frequency range 0.0067-0.05 Hz. Wavelet semblance, the cosine of WTP, was used to make the values comparable to PRx, and the new index was termed wavelet pressure reactivity index (wPRx). The traditional PRx, the running correlation coefficient between ABP and ICP, was calculated. The result showed a significant linear relationship between wPRx and PRx in the PEEP group (R = 0.88) and non-PEEP group (R = 0.56). In the non-PEEP group, wPRx showed better performance than PRx in distinguishing cerebral perfusion pressure (CPP) above and below the lower limit of autoregulation (LLA). When CPP was decreased below LLA, wPRx increased from 0.43 ± 0.28 to 0.69 ± 0.12 (P = 0.003) while PRx increased from 0.07 ± 0.21 to 0.27 ± 0.37 (P = 0.04). Moreover, wPRx provided a more stable result than PRx (SD of PRx was 0.40 ± 0.07, and SD of wPRx was 0.28 ± 0.11, P = 0.001). Assessment of CA using wavelet-derived phase shift between ABP and ICP is feasible

Multichannel near infrared spectroscopy indicates regional variations in cerebral autoregulation in infants supported on extracorporeal membrane oxygenation

Assessing noninvasively cerebral autoregulation, the protective mechanism of the brain to maintain constant cerebral blood flow despite changes in blood pressure, is challenging. Infants on life support system (ECMO) for cardiorespiratory failure are at risk of cerebral autoregulation impairment and consequent neurological problems. We measured oxyhaemoglobin concentration (HbO(2)) by multichannel (12 channels) near-infrared spectroscopy (NIRS) in six infants during sequential changes in ECMO flow. Wavelet cross-correlation (WCC) between mean arterial pressure (MAP) and HbO(2) was used to construct a time-frequency representation of the concordance between the two signals to assess the nonstationary aspect of cerebral autoregulation and investigate regional variations. Group data showed that WCC increases with decreasing ECMO flow indicating higher concordance between MAP and HbO(2) and demonstrating loss of cerebral autoregulation at low ECMO flows. Statistically significant differences in WCC were observed between channels placed on the right and left scalp with channels on the right exhibiting higher values of WCC suggesting that the right hemisphere was more susceptible to disruption of cerebral autoregulation. Multichannel NIRS in conjunction with wavelet analysis methods can be used to assess regional variations in dynamic cerebral autoregulation with important clinical application in the management of critically ill children on life support systems

Cerebral autoregulation, brain injury, and the transitioning premature infant

Improvements in clinical management of the preterm infant have reduced the rates of the two most common forms of brain injury, such as severe intraventricular hemorrhage and white matter injury, both of which are contributory factors in the development of cerebral palsy. Nonetheless, they remain a persistent challenge and are associated with a significant increase in the risk of adverse neurodevelopment outcomes. Repeated episodes of ischemia–reperfusion represent a common pathway for both forms of injury, arising from discordance between systemic blood flow and the innate regulation of cerebral blood flow in the germinal matrix and periventricular white matter. Nevertheless, establishing firm hemodynamic boundaries, as a part of neuroprotective strategy, has challenged researchers. Existing measures either demonstrate inconsistent relationships with injury, as in the case of mean arterial blood pressure, or are not feasible for long-term monitoring, such as cardiac output estimated by echocardiography. These challenges have led some researchers to focus on the mechanisms that control blood flow to the brain, known as cerebrovascular autoregulation. Historically, the function of the cerebrovascular autoregulatory system has been difficult to quantify; however, the evolution of bedside monitoring devices, particularly near-infrared spectroscopy, has enabled new insights into these mechanisms and how impairment of blood flow regulation may contribute to catastrophic injury. In this review, we first seek to examine how technological advancement has changed the assessment of cerebrovascular autoregulation in premature infants. Next, we explore how clinical factors, including hypotension, vasoactive medications, acute and chronic hypoxia, and ventilation, alter the hemodynamic state of the preterm infant. Additionally, we examine how developmentally linked or acquired dysfunction in cerebral autoregulation contributes to preterm brain injury. In conclusion, we address exciting new approaches to the measurement of autoregulation and discuss the feasibility of translation to the bedside

Dynamic cerebral autoregulation reproducibility is affected by physiological variability

Parameters describing dynamic cerebral autoregulation (DCA) have limited reproducibility. In an international, multi-center study, we evaluated the influence of multiple analytical methods on the reproducibility of DCA. Fourteen participating centers analyzed repeated measurements from 75 healthy subjects, consisting of 5 min of spontaneous fluctuations in blood pressure and cerebral blood flow velocity signals, based on their usual methods of analysis. DCA methods were grouped into three broad categories, depending on output types: (1) transfer function analysis (TFA); (2) autoregulation index (ARI); and (3) correlation coefficient. Only TFA gain in the low frequency (LF) band showed good reproducibility in approximately half of the estimates of gain, defined as an intraclass correlation coefficient (ICC) of > 0.6. None of the other DCA metrics had good reproducibility. For TFA-like and ARI-like methods, ICCs were lower than values obtained with surrogate data (p less than 0.05). For TFA-like methods, ICCs were lower for the very LF band (gain 0.38 ± 0.057, phase 0.17 ± 0.13) than for LF band (gain 0.59 ± 0.078, phase 0.39 ± 0.11, p ? 0.001 for both gain and phase). For ARI-like methods, the mean ICC was 0.30 ± 0.12 and for the correlation methods 0.24 ± 0.23. Based on comparisons with ICC estimates obtained from surrogate data, we conclude that physiological variability or non-stationarity is likely to be the main reason for the poor reproducibility of DCA parameters. Copyright © 2019 Sanders, Elting, Panerai, Aries, Bor-Seng-Shu, Caicedo, Chacon, Gommer, Van Huffel, Jara, Kostoglou, Mahdi, Marmarelis, Mitsis, Müller, Nikolic, Nogueira, Payne, Puppo, Shin, Simpson, Tarumi, Yelicich, Zhang and Claassen

A Nonlinear Dynamic Approach Reveals a Long-Term Stroke Effect on Cerebral Blood Flow Regulation at Multiple Time Scales

Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary physiological signals

Bifurcation in blood oscillatory rhythms for patients with ischemic stroke:a small scale clinical trial using laser Doppler flowmetry and computational modelling of vasomotion

We describe application of spectral analysis of laser Doppler flowmetry (LDF) signals to investigation of cerebrovascular haemodynamics in patients with post-acute ischemic stroke (AIS) and cerebrovascular insufficiency. LDF was performed from 3 to 7 days after the onset of AIS on forehead in the right and left supraorbital regions in patients. Analysis of LDF signals showed that perfusion in the microvasculature in AIS patients was lower than that in patients with cerebrovascular insufficiency. As a result of wavelet analysis of the LDF signals we obtained activation of the vasomotion in the frequency range of myogenic oscillation of 0.1 Hz and predominantly nutritive regime microcirculation after systemic thrombolytic therapy of the AIS patients. In case of significant stroke size, myogenic activity and nutritive pattern microhaemodynamics were reduced, in some cases non-nutritive pattern and/or venular stasis was revealed. Wavelet analysis of the LDF signals also showed asymmetry in wavelet spectra of the LDF signals obtained in stroke-affected and unaffected hemispheres in the AIS patients. A mechanism underlying the observed asymmetry was analysed by computational modelling of vasomotion developed in (Arciero & Secomb, 2012). We applied this model to describe relaxation oscillation of arteriole diameter which is forced by myogenic oscillation induced by synchronous calcium oscillation in vascular smooth muscle cells. Calculation showed that vasomotion frequency spectrum at the low-frequency range (0.01 Hz) is reciprocally modulated by myogenic oscillation (0.1 Hz) that correlates with experimental observation of inter-hemispheric variation in the LDF spectrum

Wavelet cross-correlation to investigate regional variations in cerebral oxygenation in infants supported on extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation can potentially affect cerebral blood flow dynamics and consequently influence cerebral autoregulation. We applied wavelet cross-correlation (WCC) between multichannel cerebral oxyhemoglobin concentration (HbO(2)) and mean arterial pressure (MAP), to assess regional variations in cerebral autoregulation. Six infants on veno-arterial (VA) ECMO were studied during sequential changes in the ECMO flows. WCC between MAP and HbO(2) for each flow period and each channel was calculated within three different frequency (wavelet scale) bands centered around 0.1, 0.16, and 0.3 Hz chosen to represent low frequency oscillations, ventilation, and respiration rates, respectively. The group data showed a relationship between maximum WCC and ECMO flow. During changes in ECMO flow, statistically significant differences in maximum WCC were found between right and left hemispheres. WCC between HbO(2) and MAP provides a useful method to investigate the dynamics of cerebral autoregulation during ECMO. Manipulations of ECMO flows are associated with regional changes in cerebral autoregulation which may potentially have an important bearing on clinical outcome