Reduction Of Cerebrovascular Reactivity Research Articles

Carotid arterial intraplaque hemorrhage and calcification influences cerebral hemodynamics

We evaluated associations between cerebral blood flow (CBF) and histopathological features in atherosclerotic lesions of the internal carotid artery. Cerebrovascular reactivity (CVR) and CBF were measured in 72 patients with unilateral carotid artery stenosis who underwent Xe-CT before carotid endarterectomy. Collateral blood flow was estimated as stump pressure. Proportions of fibrous tissue, intraplaque hemorrhage (IPH), and calcification were pathologically compared with the entire plaque body. The Spearman's rank test and stepwise multiple linear regression analysis revealed that the IPH rate significantly and negatively correlated with CBF, whereas the calcification rate positively correlated with CVR. One-way analysis of variance showed that IPH and the absence of calcification might confer a risk for CBF and CVR reduction. Thus, not only the stenosis rate but also the degree of IPH and calcification in carotid arterial plaque are notable risk factors for ischemic stroke.

Abstracts for Canadian Stroke Conference

Specogna, AV; Patten, SB; Hill, MD; University of Calgary, Calgary, AB Background: Previous studies have examined predictors of treatment costs after Spontaneous Intracerebral Hemorrhage (ICH) in various countries and healthcare systems. Currently however, there is no clear understanding of which factors are associated with cost in any Canadian setting and thus no way of understanding how to plan ICH healthcare spending. Methods: We used a retrospective case series study design and adjusted linear regression to investigate if an association existed between the total cost of ICH hospital care in a Canadian health centre and age (years), gender (female vs. male), Charlson Comorbidity Index (0 vs. ≥1), in-hospital mortality (alive vs. dead), and having surgery (no vs. yes). Economic, treatment, and patient data were obtained from administrative sources. Total inflation-adjusted hospital cost per discharge was estimated in Canadian Dollars and log transformed for all analyses. Results: Analyses were performed using 987 consecutive ICH discharges from 1999 to 2008. The total cost of ICH hospital care was highly variable (mean cost per discharge=$25,613.96±$36,116.33; min $446.81 to max $326,275.10). Older age (β=–0.0057; 95% CI: –0.0103 to –0.0011) and death in hospital (β=–0.4859; 95% CI: –0.6357 to –0.3342) were significantly associated with lower total hospital cost per discharge. Whereas Charlson Comorbidity Index of ≥1 (β=0.6489; 95% CI: 0.5063 to 0.7916) and having surgery (β=1.3552; 95% CI: 1.1893 to 1.5210) were significantly associated with higher total hospital cost per discharge. Gender was not significantly associated with cost (β=0.0727; 95% CI: –0.0679 to 0.2134). Conclusions: To our knowledge this is the first study to examine predictors of ICH treatment costs in Canada. In a Canadian health centre, ICH treatment costs were significantly associated with patient age, level of comorbidity, in-hospital mortality, and surgical treatment. This study provides evidence that it may be reasonable to consider …

Measurement of Cerebrovascular Reactivity in Pediatric Patients With Cerebral Vasculopathy Using Blood Oxygen Level-Dependent MRI

Cerebrovascular reactivity (CVR) is an indicator of cerebral hemodynamics. In adults with cerebrovascular disease, impaired CVR has been shown to be associated with an increased risk of stroke. In children, however, CVR studies are not common. This may be due to the difficulties and risks associated with current CVR study methodologies. We have previously described the application of precise control of end-tidal carbon dioxide partial pressure for CVR studies in adults. Our aim is to report initial observations of CVR studies that were performed as part of a larger observational study regarding investigations in pediatric patients with cerebral vascular disease. Thirteen patients between the ages of 10 and 16 years (10 with a diagnosis of Moyamoya vasculopathy and 3 with confirmed, or suspected, intracranial vascular stenosis) underwent angiography, MRI, and functional blood oxygen level-dependent MRI mapping of CVR to hypercapnia. The results of the CVR study were then related to both the structural imaging and clinical status. Sixteen blood oxygen level-dependent MRI CVR studies were performed successfully in 13 consecutive patients. Twelve of the 13 patients with angiographic abnormalities also had CVR deficits in the corresponding downstream vascular territories. CVR deficits were also seen in 8 of 9 symptomatic patients and 2 of the asymptomatic patients. Notably, in patients with abnormalities on angiography, the reductions in CVR extended beyond the ischemic lesions identified with MR structural imaging into normal-appearing brain parenchyma. This is the first case series reporting blood oxygen level-dependent MRI CVR in children with cerebrovascular disease. CVR studies performed so far provide information regarding hemodynamic compromise, which complements traditional clinical assessment and structural imaging.

Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity.

Neckties and Cerebrovascular Reactivity in Young Healthy Males: A Pilot Randomised Crossover Trial

Background. A necktie may elevate intracranial pressure through compression of venous return. We hypothesised that a tight necktie would deleteriously alter cerebrovascular reactivity. Materials and Methods. A necktie was simulated using bespoke apparatus comprising pneumatic inner-tube with aneroid pressure-gauge. Using a randomised crossover design, cerebrovascular reactivity was measured with the “pseudo-tie” worn inflated or deflated for 5 minutes (simulating tight/loose necktie resp.). Reactivity was calculated using breath hold index (BHI) and paired “t” testing used for comparative analysis. Results. We enrolled 40 healthy male volunteers. There was a reduction in cerebrovascular reactivity of 0.23 units with “tight” pseudotie (BHI loose 1.44 (SD 0.48); BHI tight 1.21 (SD 0.38) P < .001). Conclusion. Impairment in cerebrovascular reactivity was found with inflated pseudo-tie. However, mean BHI is still within a range of considered normal. The situation may differ in patients with vascular risk factors, and confirmatory work is recommended.

Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer's disease.

Epidemiologic evidence and postmortem studies of cerebral amyloid angiopathy suggest that vascular dysfunction may play an important role in the pathogenesis of Alzheimer's disease (AD). However, alterations in vascular function under in vivo conditions are poorly understood. In this study, we assessed cerebrovascular-reactivity (CVR) in AD patients and age-matched controls using CO(2)-inhalation while simultaneously acquiring Blood-Oxygenation-Level-Dependent (BOLD) MR images. Compared with controls, AD patients had widespread reduction in CVR in the rostral brain including prefrontal, anterior cingulate, and insular cortex (p < 0.01). The deficits could not be explained by cardiovascular risk factors. The spatial distribution of the CVR deficits differed drastically from the regions of cerebral blood flow (CBF) deficits, which were found in temporal and parietal cortices. Individuals with greater CVR deficit tended to have a greater volume of leukoaraiosis as seen on FLAIR MRI (p = 0.004). Our data suggest that early AD subjects have evidence of significant forebrain vascular contractility deficits. The localization, while differing from CBF findings, appears to be spatially similar to PIB amyloid imaging findings.

Early morning impairment in cerebral autoregulation and cerebrovascular CO2 reactivity in healthy humans: relation to endothelial function

The reduction in cerebrovascular reactivity to CO(2) and/or endothelial function that occurs in the early hours after waking are potential causes for the increased risk for cardiovascular events at this time point. It is unknown whether cerebral autoregulation is reduced in the morning. We tested the hypothesis that early morning reduction in endothelium-dependent vascular reactivity would be linked to changes in cerebrovascular reactivity to CO(2) and cerebral autoregulation (CA). Overnight changes in a dynamic cerebral autoregulation index (ARI) were determined from continuous recordings of blood flow velocity in the middle cerebral artery (MCAv) and arterial blood pressure (BP) during transiently induced hypotension in 20 individuals. Frontal cortical oxygenation (near infrared spectroscopy) and cerebral haemodynamics were also monitored during hypercapnia and before and during 3 min of active standing. Brachial artery flow-mediated endothelium-dependent vasodilatation (FMD) and endothelium-independent dilatation (NFMD) were also monitored. From evening to morning, there was a significant lowering in ARI (5.3 +/- 0.5 versus 4.7 +/- 0.6 a.u.; P < 0.05), cerebrovascular reactivity to CO(2) (5.3 +/- 0.6 versus 4.6 +/- 1.1% mmHg(-1); P < 0.05) and FMD (7.6 +/- 0.9 versus 6.0 +/- 1.4%; P < 0.05). The lowered FMD was related to the decrease in cerebrovascular reactivity to CO(2) (r = 0.76; P < 0.05). Transient reductions in morning MCAv and cortical oxyhaemoglobin concentrations were observed upon resuming a supine-to-upright position (P < 0.05 versus evening). The early morning reduction in cerebral autoregulation may facilitate the onset of cerebrovascular accidents; this may be of particular relevance to at-risk groups, especially upon resuming the upright position.

Cerebrovascular Reactivity in Major Depression: A Pilot Study

There are a growing number of reports that depression may increase the risk of stroke. Little is known, however, about the pathophysiologic mechanisms underlying this association. Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus and is an important mechanism to provide constant cerebral blood flow. We hypothesized that CVR is reduced in patients with major depression, thus contributing to the association between depression and stroke. We assessed CVR in 33 patients with unipolar depression and 26 healthy controls by calculating the increase in cerebral blood flow velocity after stimulation with acetazolamide. Blood flow velocities were measured by transcranial Doppler ultrasound. Cerebrovascular reactivity was significantly reduced in depressed patients. Smoking was also associated with a significant reduction in CVR, whereas age and gender had no significant influence. Cerebrovascular reactivity appears to be impaired in major depression. Further studies should clarify the mechanisms leading to this reduced CVR.

Low-Dose Endotoxin Reduces Human Cerebrovascular Reactivity and Produces Procoagulant State

P118 Stroke risk is increased in the presence of some infections. We studied potential mechanisms linking infections and stroke risk. We used endotoxin, a component of gram negative bacteria, as a standardized inflammatory stimulus. We infused low-dose endotoxin (1ng/kg) as a bolus in four healthy men, and analyzed cerebrovascular and hemostatic effects over 24 hours. We measured cerebral vasomotor reactivity, using transcranial Doppler ultrasonography to calculate breath-holding index (BHI); the latter consists of the percent change of middle cerebral artery blood flow velocity over time during breath holding. We also measured thrombin-antithrombin complexes (TAT, an index of thrombin generation), and soluble e-selectin (a marker of endothelial activation). Following infusion of endotoxin, there were substantial physiological changes primarily at three to six hours post-infusion. Temperature peaked at 100 °F (p&lt;.05), with no significant change in mean arterial pressure. BHI showed maximum decline from 1.55 ± 0.88 to 0.33 ± 0.35 %/sec (p&lt;.05). TAT levels increased from 3.0 ± 0.9 to 41.0 ± 21.1 ug/ml (p&lt;.05). Soluble e-selectin levels increased from 66.6 ± 35.2 to 207.4 ± 78.9 ug/ml (p&lt;.05). These findings indicate that a standardized low-dose inflammatory stimulus produces a marked decline in human cerebrovascular reactivity while simultaneously inducing a procoagulant state with endothelial activation . The reduction in cerebrovascular reactivity combined with a procoagulant state may contribute to increased stroke risk in this setting.

Reduction of cerebrovascular reactivity during hypercapnia.

The effects on cerebral blood flow of alpha- or beta-adrenergic receptor stimulation of cerebral vessels were examined in 13 unanesthetized goats before and during hypercapnia produced by inhalation of 10% CO2 in air. This procedure increased the PCO2 from 34 to 52 and was accompanied by a fall in pH from 7.39 to 7.26. Electrical stimulation of the cervical sympathetic nerve and injections of norepinephrine and tyramine into the internal maxillary artery produced reductions in cerebral blood flow that were abolished or reduced in hypercapnia. The increase in cerebral blood flow in response to beta-adrenergic stimulation with isoproterenol was also reduced. Hypercapnia caused a similar depression of the constrictor and dilatory effects of the nonadrenergic drugs vasopressin and diazoxide. The results show a decreased response of cerebral vessels to adrenergic and nonadrenergic stimuli in hypercapnia. The findings do not suggest any difference between the refractoriness of cerebral vessels in hypercapnia and that described in other vascular beds.