Cerebral blood flow velocity during mental activation: interpretation with different models of the passive pressure-velocity relationship.

The passive relationship between arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) has been expressed by a single parameter [cerebrovascular resistance (CVR)] or, alternatively, by a two-parameter model, comprising a resistance element [resistance-area product (RAP)] and a critical closing pressure (CrCP). We tested the hypothesis that the RAP+CrCP model can provide a more consistent interpretation to CBFV responses induced by mental activation tasks than the CVR model. Continuous recordings of CBFV [bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal CO(2) (EtCO(2)) were performed in 13 right-handed healthy subjects (aged 21-43 yr), in the seated position, at rest and during 10 repeated presentations of a word generation and a constructional puzzle paradigm that are known to induce differential cortical activation. Due to its small relative change, the CBFV response can be broken down into standardized subcomponents describing the relative contributions of ABP, CVR, RAP, and CrCP. At rest and during activation, the RAP+CrCP model suggested that RAP might reflect myogenic activity in response to the ABP transient, whereas CrCP was more indicative of metabolic control. These different influences were not reflected by the CVR model, which indicated a predominantly metabolic response. Repeated-measures multi-way ANOVA showed that CrCP (P = 0.025), RAP (P = 0.046), and CVR (P = 0.002) changed significantly during activation. CrCP also had a significant effect of paradigm (P = 0.045) but not hemispheric dominance. Both RAP (P = 0.039) and CVR (P = 0.0008) had significant effects of hemispheric dominance but were not sensitive to the different paradigms. Subcomponent analysis can help with the interpretation of CBFV responses to mental activation, which were found to be dependent on the underlying model of the passive ABP-CBFV relationship.

Cardiac baroreceptor sensitivity predicts long-term outcome after acute ischemic stroke.

BACKGROUND AND PURPOSE: The baroreceptor reflex arc is important in the short-term regulation of the cardiovascular system, and small studies have reported impaired cardiac baroreceptor sensitivity (BRS) after acute stroke. However, the prognostic significance of impaired BRS is uncertain. METHODS: One hundred twenty-four patients underwent simultaneous ECG and noninvasive beat-to-beat blood pressure (BP) monitoring within 72 hours of neuroradiologically confirmed acute ischemic stroke. Cardiac BRS was assessed from the combined alpha-index by means of power spectral analysis techniques. Baseline data for acute stroke patients were compared with those of a control group matched for age, sex, and casual BP. Patients were followed up for a median of 1508 days (range, 9 to 2656 days), and outcome was compared between patients with and without impaired BRS. RESULTS: Median BRS values were significantly lower in stroke patients than in controls (5 [interquartile range, 3.5 to 7.4] versus 6.2 [interquartile range, 4.5 to 8.3] ms/mm Hg; P=0.04). Sixty-one (33 male) patients (mean age, 70.2 [SD 10.5] years) had impaired BRS (< or =5.0 ms/mm Hg) compared with 63 (35 male) patients (mean age, 70.6 [SD 11.7] years) without impaired BRS (>5.0 ms/mm Hg). Stroke patients with impaired BRS values had a significantly poorer prognosis (28% versus 8% mortality rate during the follow-up period) although there were no differences in age, stroke severity, stroke type, or casual or 24-hour BP parameters between the 2 groups. CONCLUSIONS: Impaired cardiac BRS is associated with increased long-term mortality after acute ischemic stroke, irrespective of age, sex, stroke type, and BP. This may reflect cardiac arrhythmias, but the mechanisms underlying this association are unknown, although therapies that improve cardiac BRS after stroke warrant further investigation.

The systemic haemodynamic and cerebral autoregulatory effects of bendrofluazide in the subacute post-stroke period.

INTRODUCTION: Little data exist on the efficacy in terms of blood pressure reduction or outcome measures for the various antihypertensive agents in patients post-stroke. In this study the effects of bendrofluazide on blood pressure levels and variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity were assessed in the sub-acute stroke period. METHODS: A total of 36 hypertensive ischaemic stroke patients were randomized to oral bendrofluazide 2.5 mg daily or matching placebo starting 10 days post-ictus and continued for 28 days. A total of 12 hypertensive controls were similarly randomized in a double-blind, crossover study, each limb being of 28 days duration. Cerebral blood flow velocity, non-invasive beat-to-beat blood pressure levels, electrocardiograms (ECGs) and transcutaneous carbon dioxide levels were measured before and at the end of each treatment period in stroke and control subjects. RESULTS: Casual blood pressure levels were not significantly reduced in stroke patients with bendrofluazide, but in the placebo group levels increased by 13 +/- 13/6 +/- 7 mmHg (P < 0.001) at study termination. In the control group, casual systolic blood pressure fell during active treatment by 12 +/- 16 mmHg (P < 0.03) compared with placebo. Dynamic cerebral autoregulation, beat-to-beat blood pressure variability and cardiac baroreceptor sensitivity did not change with bendrofluazide or placebo in either the stroke patients or controls. CONCLUSION: Bendrofluazide does not appear to be an effective hypotensive agent in the sub-acute post-stroke period but may limit the blood pressure rise seen during stroke recovery. Bendrofluazide however does not adversely influence dynamic cerebral autoregulation, blood pressure variability or cardiac baroreceptor sensitivity in either strokes or control subjects.

Cerebral autoregulation indices are unimpaired by hypertension in middle aged and older people.

BACKGROUND: Hypertension is known to increase the limits of static cerebral autoregulation (CA) but its effects on other aspects of CA such as efficiency and latency are unknown. In this study we test the hypothesis that dynamic cerebral autoregulation and the efficiency of static cerebral autoregulation are impaired by untreated hypertension. METHODS: Cerebral blood flow velocity was recorded using transcranial Doppler ultrasound, along with noninvasive beat-to-beat blood pressure (BP), electrocardiogram, and transcutaneous carbon dioxide levels, with subjects at rest and during isometric hand grip, thigh cuff, and the Valsalva maneuver. Static and dynamic CA indices were calculated. RESULTS: No significant difference was seen in static or dynamic CA indices between normotensive and hypertensive groups for any pressor or depressor stimulus. Spearman's rank correlation showed no relation between static or dynamic CA indices and systemic BP levels for all maneuvers, but a significant relationship between age and static CA index, determined using isometric handgrip (P =.002), was found. CONCLUSIONS: In middle-aged and older people, sustained untreated hypertension does not alter dynamic CA or the efficiency of static CA within the BP limits studied.

Motor and sensory conduction failure in overlap of Guillain-Barré and Miller Fisher syndrome: two simultaneous cases.

We report 2 patients diagnosed simultaneously with an overlap of Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS), who had anti-GT1a, anti-GQ1b, anti-GD1a and anti-GD1b antibodies. There was no identifiable specific preceding infection. Both patients presented with upper and lower limb paresthesias and severe weakness, bulbar and facial weakness, ophthalmoparesis and areflexia. In one, electrophysiology demonstrated multifocal conduction blocks (CBs) and mild motor conduction velocity slowing in intermediate segments and absent sensory nerve action potentials (SNAPs). The patient improved rapidly and fully recovered within 18 days from onset. CBs resolved, distal compound muscle action potential (CMAP) amplitudes increased and SNAPs normalized on subsequent testing. In the other patient, initial studies showed low/normal CMAPs, with absent SNAPs, without demyelinating features. This patient fully recovered within 21 days from onset. CMAPs markedly increased, SNAPs improved marginally. These 2 patients exhibited features indicative of the pathophysiological mechanism of conduction failure in motor and sensory fibers. This phenomenon relates to rapidly resolving CBs possibly induced by the transitory and limited attack of antiganglioside antibodies at the axolemma of the nodes of Ranvier not progressing to axonal degeneration. These cases widen the range of GBS subtypes in which reversible conduction failure has been described, to include overlap syndromes with MFS. The factors determining the electrophysiology, as well as the rate, degree and quality of recovery in GBS subtypes remain uncertain at the present time.

Multiple coherence of cerebral blood flow velocity in humans.

The coherence function has been used in transfer function analysis of dynamic cerebral autoregulation to assess the statistical significance of spectral estimates of gain and phase frequency response. Interpretation of the coherence function and choice of confidence limits has not taken into account the intrinsic nonlinearity represented by changes in cerebrovascular resistance due to vasomotor activity. For small spontaneous changes in arterial blood pressure (ABP), the relationship between ABP and cerebral blood flow velocity (CBFV) can be linearized, showing that corresponding changes in cerebrovascular resistance should be included as a second input variable. In this case, the standard univariate coherence function needs to be replaced by the multiple coherence, which takes into account the contribution of both inputs to explain CBFV variability. With the use of two different indicators of cerebrovascular resistance index [CVRI = ABP/CBFV and the resistance-area product (RAP)], multiple coherences were calculated for 42 healthy control subjects, aged 20 to 40 yr (28 +/- 4.6 yr, mean +/- SD), at rest in the supine position. CBFV was measured in both middle cerebral arteries, and ABP was recorded noninvasively by finger photoplethysmography. Results for the ABP + RAP inputs show that the multiple coherence of CBFV for frequencies <0.05 Hz is significantly higher than the corresponding values obtained for univariate coherence (P < 10(-5)). Corresponding results for the ABP + CVRI inputs confirm the principle of multiple coherence but are less useful due to the interdependence between CVRI, ABP, and CBFV. The main conclusion is that values of univariate coherence between ABP and CBFV should not be used to reject spectral estimates of gain and phase, derived from small fluctuations in ABP, because the true explained power of CBFV in healthy subjects is much higher than what has been usually predicted by the univariate coherence functions.

Assessment of cerebral autoregulation from ectopic heartbeats.

Transfer function analysis of spontaneous fluctuations in BP (blood pressure) and CBFV (cerebral blood flow velocity) has been widely used to study dynamic CA (cerebral autoregulation). The inverse Fourier transform and its integral, giving the impulse and step responses, have been used to gain perspective of the state of dynamic CA from the frequency and time domains respectively. The occurrence of ectopic heartbeats in the data has usually been treated as an artefact. Data containing multiple ectopic heartbeats were selected from a data set compiled for an acute stroke study which also included bilateral middle CBFV, concurrent surface ECG and non-invasive beat-to-beat BP recordings. Transfer function analysis and impulse and step responses were calculated from these data by (i) retaining ectopic heartbeats, (ii) after removal of ectopic heartbeats and replacement by linear interpolation, and (iii) using a narrow window of data surrounding selected ectopic heartbeats. Coherent averaging of the raw data of the selected ectopic heartbeats also allowed direct visualization of the relationship between BP changes and CBFV. The impulse and step responses were similar in shape whether or not ectopic heartbeats had been removed and showed characteristics of active dynamic CA. Removal of ectopic heartbeats from the CBFV and BP tracings, by linear interpolation or other methods, is not necessary to provide reliable estimates of dynamic autoregulation in subjects with ectopic heartbeat rates of up to eight per min. Additionally, impulse-like disturbances of BP induced by single-beat ectopic heartbeats provide enough information to characterize the autoregulatory response of the subject in agreement with more traditional methods of dynamic autoregulation assessment.

Bendrofluazide fails to reduce elevated blood pressure levels in the immediate post-stroke period.

INTRODUCTION: Blood pressure (BP) levels, beat-to-beat blood pressure variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity are frequently abnormal following acute stroke and are associated with an adverse short- and long-term prognosis. Thiazide diuretics are effective antihypertensive agents in preventing primary and secondary stroke, but their hypotensive and cerebral autoregulatory effects in the immediate post-stroke period have not been studied. METHODS: Thirty-seven hypertensive neuroradiologically proven ischaemic stroke patients were randomized in a double-blind, placebo controlled, parallel group study to bendrofluazide 2.5 mg daily or matching placebo, within 96 h of stroke onset, for a 7-day period. Casual and non-invasive beat-to-beat arterial BP levels, cerebral blood flow velocity, ECG and transcutaneous carbon dioxide levels were measured within 70 +/- 20 h of cerebral infarction and again 7 days later. Dynamic cerebral autoregulatory indices, pulse interval, BP variability and cardiac baroreceptor sensitivity were also calculated. RESULTS: Small, non-significant falls were seen in casual and beat-to-beat BP levels over the 7-day period in both active and placebo-treated patients with no differences between treatments. No significant changes were seen in dynamic cerebral autoregulation or in cardiac baroreceptor sensitivity during the follow-up in either group. CONCLUSION: Following acute ischaemic stroke, the standard dose of bendrofluazide at 2.5 mg daily in this study sample did not lower systemic BP levels over the subsequent 7-day period. There was no evidence that bendrofluazide significantly altered cerebral autoregulation or improved cardiac baroreceptor sensitivity post-ictus. Bendrofluazide appears to be an ineffective hypotensive agent at the standard dosage in the initial post-stroke period.

Acute stroke hypertension: current and future management.

The management of hypertension in acute stroke remains a hotly debated issue. Clinical practice varies widely between physicians, and both European and US guidelines reflect the uncertainty surrounding this question. Although there is a large amount of data that, on the whole, tends to support a connection between poststroke hypertension and hypotension and worse outcome, there have been few randomized controlled trials to clarify whether pharmacologic intervention is safe or beneficial. Data from secondary prevention trials convincingly demonstrate the benefits of controlling hypertension after a stroke but do not guide us as to how early to implement therapy. There is even less information from trials regarding the use of pressor agents in hypotensive stroke patients. This review discusses the dilemmas in the management of acute stroke hypertension and summarizes the available evidence from studies involving a variety of both depressor and pressor agents. The authors detail the ongoing studies that will help to answer some of the outstanding questions and summarizes the existing guidelines regarding indications for acute stroke blood pressure manipulation currently available to physicians.

Cerebral and systemic hemodynamic changes during cognitive and motor activation paradigms.

Cognitive and/or sensorimotor stimulations of the brain induce increases in cerebral blood flow that are usually associated with increased metabolic demand. We tested the hypothesis that changes in arterial blood pressure (ABP) and arterial Pco(2) also take place during brain activation protocols designed to induce hemispheric lateralization, leading to a pressure-autoregulatory response in addition to the metabolic-driven changes usually assumed by brain stimulation paradigms. Continuous recordings of cerebral blood flow velocity [CBFV; bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco(2) (Pet(CO(2))) were performed in 15 right-handed healthy subjects (aged 21-43 yr), in the seated position, at rest and during 10 repeated presentations of a word generation and a constructional puzzle paradigm that are known to induce differential cortical activation. Derived variables included heart rate, cerebrovascular resistance, critical closing pressure, resistance area product, and the difference between the right and left MCA recordings (CBFV(R-L)). No adaptation of the CBFV(R-L) difference was detected for the repeated presentation of 10 activation tasks, for either paradigm. During activation with the word generation tasks, CBFV changed by (mean +/- SD) 9.0 +/- 3.7% (right MCA, P = 0.0007) and by 12.3 +/- 7.6% (left MCA, P = 0.0007), ABP by 7.7 +/- 6.0 mmHg (P = 0.0007), heart rate by 7.1 +/- 5.3 beats/min (P = 0.0008), and Pet(CO(2)) by -2.32 +/- 2.23 Torr (P = 0.002). For the puzzle paradigm, CBFV changed by 13.9 +/- 6.6% (right MCA, P = 0.0007) and by 11.5 +/- 6.2% (left MCA, P = 0.0007), ABP by 7.1 +/- 8.4 mmHg (P = 0.0054), heart rate by 7.9 +/- 4.6 beats/min (P = 0.0008), and Pet(CO(2)) by -2.42 +/- 2.59 Torr (P = 0.001). The word paradigm led to greater left hemispheric dominance than the right hemispheric dominance observed with the puzzle paradigm (P = 0.004). We concluded that significant changes in ABP and Pet(CO(2)) levels occur during brain activation protocols, and these contribute to the evoked change in CBFV. A pressure-autoregulatory response can be observed in addition to the hemodynamic changes induced by increases in metabolic demand. Simultaneous changes in Pco(2) and heart rate add to the complexity of the response, indicating the need for more detailed modeling and better understanding of brain activation paradigms.

Dynamic cerebral autoregulation during brain activation paradigms.

Dynamic cerebral autoregulation (CA) describes the transient response of cerebral blood flow (CBF) to rapid changes in arterial blood pressure (ABP). We tested the hypothesis that the efficiency of dynamic CA is increased by brain activation paradigms designed to induce hemispheric lateralization. CBF velocity [CBFV; bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco(2) were continuously recorded in 14 right-handed healthy subjects (21-43 yr of age), in the seated position, at rest and during 10 repeated presentations (30 s on-off) of a word generation test and a constructional puzzle. Nonstationarities were not found during rest or activation. Transfer function analysis of the ABP-CBFV (i.e., input-output) relation was performed for the 10 separate 51.2-s segments of data during activation and compared with baseline data. During activation, the coherence function below 0.05 Hz was significantly increased for the right MCA recordings for the puzzle tasks compared with baseline values (0.36 +/- 0.16 vs. 0.26 +/- 0.13, P < 0.05) and for the left MCA recordings for the word paradigm (0.48 +/- 0.23 vs. 0.29 +/- 0.16, P < 0.05). In the same frequency range, significant increases in gain were observed during the puzzle paradigm for the right (0.69 +/- 0.37 vs. 0.46 +/- 0.32 cm.s(-1).mmHg(-1), P < 0.05) and left (0.61 +/- 0.29 vs. 0.45 +/- 0.24 cm.s(-1).mmHg(-1), P < 0.05) hemispheres and during the word tasks for the left hemisphere (0.66 +/- 0.31 vs. 0.39 +/- 0.15 cm.s(-1).mmHg(-1), P < 0.01). Significant reductions in phase were observed during activation with the puzzle task for the right (-0.04 +/- 1.01 vs. 0.80 +/- 0.86 rad, P < 0.01) and left (0.11 +/- 0.81 vs. 0.57 +/- 0.51 rad, P < 0.05) hemispheres and with the word paradigm for the right hemisphere (0.05 +/- 0.87 vs. 0.64 +/- 0.59 rad, P < 0.05). Brain activation also led to changes in the temporal pattern of the CBFV step response. We conclude that transfer function analysis suggests important changes in dynamic CA during mental activation tasks.

Influence of controlled breathing patterns on cerebrovascular autoregulation and cardiac baroreceptor sensitivity.

Transfer function analysis has become one of the main techniques to study the dynamic relationship between cerebral blood flow and arterial blood pressure, but the influence of different respiratory rates on cerebral blood flow has not been fully investigated. In 14 healthy volunteers, middle cerebral artery blood flow velocity, recorded using transcranial Doppler ultrasound, non-invasive beat-to-beat Finapres blood pressure, ECG and end-tidal CO(2) ( P ECTO(2)) levels were recorded with subjects resting supine and breathing spontaneously or at controlled rates of 6, 10 and 15 breaths/min. Transfer function analysis and impulse and step responses were computed at each respiratory rate. P ECTO(2) levels tended to fall slightly during paced respiration, especially at 15 breaths/min. Controlled breathing rates did not alter transfer function analysis in the frequency range below 0.08 Hz but, above this frequency, the coherence function contained significant peaks corresponding to the respiratory frequencies. The impulse response was similar at all breathing rates, but the step response was characteristic of more efficient autoregulation with reduced P ECTO(2) levels associated with increasing respiratory rate. The effects of breathing rate and rhythmicity and P ECTO(2) must be considered in studies of cerebral autoregulation.