Cerebral Vasodilatory Capacity Research Articles

Older adults with reduced cerebrovascular reactivity exhibit high white matter hyperintensity burden

Cerebrovascular reactivity (CVR) deficits may contribute to small vessel disease, such as white matter hyperintensities (WMH). Moreover, apolipoprotein-e4 (APOE4) carriers at genetic risk for Alzheimer’s disease exhibit cerebrovascular dysfunction relative to non-carriers. We examined whether older adults, and APOE4 carriers specifically, with diminished CVR would exhibit higher WMH burden. Independently living older adults (N = 125, mean age = 69.2 years; SD = 7.6; 31.2% male) free of dementia or clinical stroke underwent brain MRI to quantify cerebral perfusion during CVR to hypercapnia and hypocapnia and determine WMH volume. Adjusting for age, sex and intracranial volume, hierarchical regression analysis revealed a significant association between whole brain CVR to hypercapnia and WMH overall [B = −.02, 95% CI (-.04, −.008), p =.003] and in APOE4 carriers [B = −.03, 95% CI (-.06, −.009), p =.009]. Findings suggest deficits in cerebral vasodilatory capacity are associated with WMH burden in older adults and future studies are warranted to further delineate the effect of APOE4 on precipitating WMH.

Acute consumption of flavanol-rich cocoa beverage improves attenuated cutaneous microvascular function in healthy young African Americans

Flavanols have beneficial effects on vascular health and we have recently demonstrated that cerebral vasodilatory capacity in healthy young African Americans (AA) is improved with acute flavanol intake relative to aged-matched Caucasian Americans (CA). However, whether the positive benefits of acute flavanol consumption would also be present in the cutaneous microvascular circulation of AA remains unknown. Thus, we hypothesized that acute consumption of flavanol-rich cocoa (FC) would improve the previously reported reduced cutaneous microvascular responses to local heating in young AA. Seven AA and seven CA participated in this double-blind crossover study. Data were collected on two different days, separated by a minimum of one week. Two intradermal microdialysis membranes were inserted in the forearm and each site was randomly assigned to receive lactated Ringer's solution or NO synthase (NOS) inhibitor. Participants were randomly assigned to consume either a non-flavanol containing (NF) beverage or FC beverage. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flux/mean arterial pressure and normalized as % maximal CVC (%CVCmax). The difference in %CVCmax between the Ringer's site and NOS inhibited site was calculated to assess NO contribution (Δ %CVCmax). In the Ringer's site, acute consumption of FC beverage improved %CVCmax during 39 °C heating when compared to NF beverage in AA (NF: 36 ± 6 vs. FC: 47 ± 5%CVCmax; P < .01) while there was similar %CVCmax during 39 °C heating between beverages in CA (NF: 55 ± 4 vs. FC: 59 ± 5%CVCmax; P = .40). During 39 °C heating, NO contribution was significantly higher with FC beverage than NF beverage in AA (NF: 27 ± 5 vs. FC: 35 ± 4 Δ %CVCmax; P = .03) while there was similar NO contribution between beverages in CA (NF: 42 ± 4 vs. FC: 45 ± 4 Δ %CVCmax; P = .36). This data suggests that acute consumption of FC could be a therapeutic solution to improve an attenuated microvascular function in young AA.

Assessment of Cerebral Vasodilatory Capacity as Part of Catheter-Based Cerebral Angiography.

Cerebral vasodilatory capacity assessment for risk stratification in patients with extracranial arterial stenosis or occlusion may be useful. We describe a new method that assesses cerebral vasodilatory capacity as part of catheter-based cerebral angiography. We prospectively assessed regional cerebral blood volume (rCBV) in the arterial distribution of interest using a controlled contrast injection in the common carotid or the subclavian arteries. rCBV maps were created using a predefined algorithm based on contrast distribution in the venous phase (voxel size: .466 mm3 ). rCBV maps were acquired again after selective administration of intra-arterial nicardipine (2.0 mg) distal to the stenosis. Two independent observers graded the change in rCBV in 10 predefined anatomical regions within the tributaries of the artery of interest (0 = reduction, 1 = no change, 2 = increase) and total rCBV change scores were summated. Twenty-five patients with internal carotid artery stenosis (n = 18; 0-90% in severity) or extracranial vertebral artery stenosis (n = 7; 0-100% in severity) were assessed. There was an increase in rCBV in a tributary of the artery of interest in 18 of 25 after intra-arterial nicardipine (mean score: 11.98; range 0-19.5). There was no change or decrease in rCBV in 7 of 25 patients. The mean rCBV change score was similar in patients with an assessment of internal carotid artery or vertebral artery distributions (12.2 ± 5.3; 11.4 ± 2.5; P = .68). Selective vasodilatory response to intra-arterial nicardipine in the affected arterial distribution during catheter-based cerebral angiography may provide new data for risk stratification.

Abstract WP22: A New Technique for the Assessment of Cerebral Vasodilatory Capacity as Part of Catheter-Based Cerebral Angiography

Background: Cerebral vasodilatory capacity assessment for risk stratification in patients with extracranial arterial stenosis or occlusion may be useful. We describe a new method that assesses cerebral vasodilatory capacity as part of catheter-based cerebral angiography. Methods: We prospectively assessed regional cerebral blood volume (rCBV) in the arterial distribution of interest using a controlled contrast injection in the common carotid or the subclavian arteries. rCBV maps were created using a predefined algorithm based on contrast distribution in the venous phase (voxel size 0.466 mm 3 ). rCBV maps were acquired again after selective administration of intra-arterial nicardipine (2.5 mg) distal to the stenosis. Two independent observers graded the change in rCBV in 10 predefined anatomical regions within the tributaries of the artery of interest (0=reduction, 1=no change, 2=increase) and total rCBV change scores were summated. The rCBV score values were averaged between the two observers for each patient. Mean arterial pressure was monitored at baseline and at 1 minute intervals post nicardipine administration for 5 minutes. Results: Twenty-five patients with internal carotid artery stenosis (n=18; 0%-90% in severity) or extracranial vertebral artery stenosis (n=7; 0%-100% in severity) were assessed. There was an increase in rCBV in a tributary of the artery of interest in 18 of 25 after intra-arterial nicardipine (mean score 11.98; range 0-19.5). There was no change or decrease in rCBV in 7 of 25 patients. The mean rCBV change score was similar in patients with assessment of internal carotid artery or vertebral artery distributions (12.2 ± 5.3; 11.4 ± 2.5; p=0.68 by ANOVA). There was an average (±SD) reduction of mean arterial pressure of 14mmHg ± 7.5 after intra-arterial nicardipine. There was no correlation between the magnitude of mean arterial pressure reduction post nicardipine (regression coefficient -0.13; p=0.38) or between the severity of stenosis (regression coefficient -0.04; p=0.29) and rCBV change scores. Conclusions: We describe a new technique for selective assessment of cerebral vasodilatory response in the affected arterial distribution during catheter-based cerebral angiography.

A New Technique for the Assessment of Cerebral Vasodilatory Capacity as Part of Catheter-Based Cerebral Angiography

Previous studies have demonstrated the value of cerebral vasodilatory capacity assessment for risk stratification in patients with extracranial arterial stenosis or occlusion. We describe a new method that assesses cerebral vasodilatory capacity as part of catheter-based cerebral angiography. We assessed regional cerebral blood volume (rCBV) in the arterial distribution of interest using a controlled contrast injection through a diagnostic catheter placed in the common carotid or the subclavian artery. rCBV maps were created using predefined algorithm based on contrast distribution in the venous phase (voxel size 0.466 mm3) into high, intermediate, low, and no detectable rCBV regions. rCBV maps were acquired again after the administration of intra-arterial nicardipine (1.5-2.5 mg), and percentage increases of the area of various grades of rCBV were calculated. Three patients with internal carotid artery stenosis (32% - 64% in severity) and 1 patient with extracranial vertebral artery stenosis (46% in severity) were assessed. There was a variable but consistent increase in the area of high rCBV in the ipsilateral hemisphere in 3 patients with internal carotid artery flow (5.5%-24.5%) and the cerebellum (9.6%) in 1 patient with vertebral artery flow assessments. The increase in high rCBV was most prominent in the patient who received 2.5 mg (24.5%) and least prominent in a patient who received 1.5 mg (5.5%) of intra-arterial nicardipine. There was a concurrent reduction in areas of intermediate and low rCBV (shift) in 3 patients, and there was an increase in all areas of rCBV grades (addition) in 1 patient. Selective assessment of cerebral vasodilatory response in the affected arterial distribution is feasible during catheter-based cerebral angiography.

Impact of correction of anemia in end-stage renal disease patients on cerebral circulation and cognitive functions.

End-stage renal disease (ESRD) patients have been associated with accelerated vascular disease of the cerebral circulation due to uremic toxins. Furthermore, anemia increases cerebral oxygen extraction fraction which impairs the cerebral vasodilatory capacity. We evaluated the effect of correction of anemia on cerebral blood flow by measuring the mean blood flow velocity, resistance index (RI), and pulsatility index (PI) in the middle cerebral artery (MCA) in relation to cognitive functions. We measured the mean blood flow velocity, RI, and PI in MCA of 120 ESRD patients when the hemoglobin (Hb) ranges between 8 and 10 g/dL and after correction of anemia to two Hb ranges between 10-11.5 g/dL and 11.5-12.5 g/dL in the same patients using transcranial Doppler (TCD) ultrasound in relation to cognitive functions assessment by Mini-Mental State Examination. We observed that there is a mild-to-moderate cognitive impairment in hemodialysis (HD) patients associated with anemia. With the improvement of anemia, the cognitive functions improved. There was an improvement of blood flow of MCA with improvement of Hb. The improvement was obvious at Stage 3 (Hb 11.5-≤12.5 g/dL) in comparison to Stage 2 (Hb 10-<11.5 g/dL) with P <0.001 at all. The optimal Hb for HD patients ranges from 11.5 to ≤12.5 g/dL which associated with better improvement of cognitive function and cerebral circulation investigated by TCD ultrasound for MCA.

Acute flavanol consumption improves the cerebral vasodilatory capacity in college-aged African Americans.

What is the central question of this study? The purpose was to determine whether acute flavanol consumption improves cerebral vasodilatory capacity during rebreathing-induced hypercapnia in African Americans. What is the main finding and its importance? The reduced cerebral vasodilatory response to hypercapnia in young healthy African Americans was improved acutely following consumption of a flavanol-rich beverage. This may have important clinical implications regarding racial differences in cerebrovascular disease risk and possible interventional approaches to offset this risk. African Americans (AAs) have increased risk for cardiovascular and cerebrovascular disease. African Americans have attenuated cerebral vasodilator capacity during hypercapnia relative to Caucasian Americans (CAs). This study tested the hypothesis, using a placebo-controlled crossover design, that acute flavanol consumption improves the range of change in cerebral vascular conductance [CVCI, (a)] and the maximal CVCI (y0) achieved during rebreathing-induced increases in end-tidal carbon dioxide tension. Fourteen college-aged AAs and 14 CAs participated. Both a and y0 were lower in AAs prior to flavanols (for a, AAs, 46 ± 16 versus CAs, 74 ± 18% CVCI, P < 0.001; and for y0, AAs, 151 ± 18 versus CAs, 176 ± 20% CVCI, P = 0.002); however, these variables were increased after flavanols such that there were no differences between groups (for a, AAs, 64 ± 19 versus CAs, 72 ± 22% CVCI, P = 0.35; and for y0, AAs, 166 ± 22 versus CAs, 176 ± 22% CVCI, P = 0.26). Both a and y0 were also lower in AAs prior to placebo (for a, AAs, 52 ± 19 versus CAs, 76 ± 15% CVCI, P = 0.002; and for y0, AAs, 156 ± 20 versus CAs, 177 ± 21% CVCI, P = 0.015), and these differences remained following placebo (for a, AAs, 52 ± 17 versus CAs, 80 ± 20% CVCI, P < 0.001; and for y0, AAs, 152 ± 18 versus CAs, 181 ± 25% CVCI, P = 0.003). These data suggest that acute flavanol consumption improves cerebral vasodilatory capacity during hypercapnia in AAs.

Attenuated Cerebral Vasodilatory Capacity in Response to Hypercapnia in Young Obese Individuals

Obese individuals are at a greater risk for the development of a variety of cardio and cerebral vascular diseases including hypertension, atherosclerosis, coronary artery disease and stroke. Furthermore, obesity is also associated with cognitive impairment and is a risk factor for dementia and Alzheimer's disease. The exact mechanisms of this elevated risk are not fully characterized; however, impaired microvascular function is believed to be a contributor. This study tested the hypothesis that the cerebral vasodilatory capacity in response to hypercapnia is reduced in obese individuals relative to age and sex matched lean counterparts. Cerebral blood velocity (CBFV) was measured using transcranial Doppler before and during rebreathing‐induced hypercapnia in obese (Obese, n=14) and lean (Lean, n=14) subjects. Cerebral vascular conductance (CVCI) was calculated as CBFV / mean arterial pressure (MAP), and a four parameter logistic regression was applied for sigmoidal curve fitting of the relationship between % change in CVCI and end‐tidal CO2 tension (PETCO2). The magnitude of hypercapnia (Δ PETCO2) during rebreathing was similar between groups (Obese 14 ± 3 mmHg vs. Lean: 15 ± 2 mmHg; P = 0.13). The maximum increase in CVCI (Obese: 155 ± 17% vs. Lean: 176 ± 23%; P &lt; 0.05) and the total range of change in CVCI (Obese: 50 ± 15% vs. Lean: 75 ± 22%; P &lt; 0.01) during rebreathing were reduced in the obese relative to the lean individuals. These data indicate that cerebral vasodilatory capacity in response to changes in PETCO2 during hypercapnia is attenuated in obese individuals compared with lean individuals.This study was supported by institutional start‐up funds awarded to R. Matthew Brothers.

Acute Natural Cocoa Consumption Improves Cerebral Vasodilatory Capacity in College‐Aged African Americans

African Americans (AA) have increased risk for cerebral vascular disease including stroke and Alzheimer's disease relative to Caucasian Americans (CA). We recently reported that relatively young AA have attenuated cerebral vasodilatory response during rebreathing‐induced hypercapnia relative to CA. This study tested the hypothesis that acute natural cocoa (NC) consumption (13g NC) restores this response in AA. 14 college‐aged AA and 14 age / sex / body mass matched CA underwent a rebreathing protocol while cerebral blood velocity (CBFV) was measured before and 2 hr post consumption of a NC‐containing drink or an isocaloric NC‐free placebo (randomized order, single‐blinded). Cerebral vascular conductance (CVCI) was calculated as CBFV / MAP. The response to rebreathing was expressed as % of baseline CVCI (% CVCI). Following NC consumption the total range of increase and the maximal increase in %CVCI during hypercapnia was increased in the AA (P&lt;0.01 for both variables) whereas there was no effect of NC consumption in the CA (P&gt;0.05 for both variables). Following NC consumption the cerebral vascular responses were similar between AA and CA (P&gt;0.05 for all variables). Consumption of the placebo beverage had no effect on cerebral vascular function in either cohort (P&gt;0.05 for all variables). These data support the hypothesis that NC consumption can acutely augment cerebral vasodilatory capacity in AA.This study was supported by institutional start‐up funds awarded to R. Matthew Brothers. The beverages were generously provided by the Hershey Company; Hershey, Pennsylvania.

Attenuated cerebral vasodilatory capacity in response to hypercapnia in college-aged African Americans.

African Americans (AAs) have increased risk for cardiovascular, cerebral vascular and metabolic disease, including hypertension, stroke, coronary artery disease, metabolic syndrome and type II diabetes, relative to Caucasian Americans (CAs). While it is accepted that endothelial function is impaired in AAs, less is known regarding their cerebral vasodilatory capacity in response to hypercapnia. We hypothesized that AAs have a reduction in the total range of change in cerebral blood flow velocity (CBFV) measured in the middle cerebral artery and an index of cerebral vascular conductance (CVCI) in response to changes in the partial pressure of end-tidal carbon dioxide () during rebreathing-induced hypercapnia when compared with CAs. Twenty-one healthy, college-aged AA (10 male) and 21 age- and sex-matched CA (10 male) subjects participated in this study. A four-parameter logistic regression was used for curve fitting the responses of CBFV and CVCI relative to changes in . The total ranges of change in CBFV (101 ± 18 versus 69 ± 23%; P < 0.001) and CVCI (83 ± 21 versus 58 ± 21%; P < 0.001) as well as the maximal increase in CBFV (205 ± 24 versus 169 ± 24%; P < 0.001) and CVCI (188 ± 30 versus 154 ± 19%; P < 0.001) were reduced during hypercapnia in AAs relative to CAs despite a similar increase in (change, 15 ± 3 versus 15 ± 3 mmHg; P = 0.65). In conclusion, these data indicate that AAs have attenuated cerebral vascular capacity to respond to hypercapnia when compared with CAs.

ADDITIONAL SURGERY FOR POSTOPERATIVE ISCHEMIC SYMPTOMS IN PATIENTS WITH MOYAMOYA DISEASE

In patients with moyamoya disease, surgery to revascularize the ischemic brain is a recommended treatment. However, there are a few patients who require additional revascularization surgery because of progression of the disease. Even patients who show no postoperative ischemic symptoms at first may experience late deterioration. We performed additional surgery for such lesions using occipital artery (OA)-posterior cerebral artery (PCA) bypass with indirect revascularization. The efficacy of the procedure is reported. We treated 3 patients with moyamoya disease who showed a transient ischemic attack after revascularization surgery. Three female patients, ranging in age from 6.0 to 35.2 years (mean age, 23.8 years) at the time of surgery, with ischemic symptoms (leg monoparesis in 2, visual impairment in 1) underwent the additional revascularization procedure. Preoperatively, all patients underwent indirect and/or direct revascularization surgery for initial treatment. All patients showed progression of the disease, especially in the PCA. OA-PCA bypass with encephalogaleodurosynangiosis and burr hole surgery were performed for postoperative ischemic symptoms. All patients showed clinical and radiological improvement. The transient ischemic attack was improved in all 3 patients. They did not complain of transient ischemic attack in the recent follow-up period. Follow-up magnetic resonance imaging showed no additional cerebral infarction. Magnetic resonance angiography showed widening of the OA and development of peripheral collateral vessels. Postoperative single-photon emission computed tomographic studies showed marked increase of uptake in both anterior cerebral artery and PCA territories. Cerebral vasodilatory capacity evaluated by an acetazolamide test also showed marked improvement. One patient showed postoperative cerebral edema as a result of focal cerebral hyperperfusion. OA-PCA anastomosis with indirect revascularization was effective for postoperative ischemia that showed symptoms in the anterior cerebral artery and PCA territories as a result of progression of a PCA lesion.

ＰＥＴによる脳循環研究とその臨床応用

Investigation of cerebral circulation and metabolism in stroke patients with PET has given clinicians useful information in interpreting the results of SPECT examinations in clinical practice. In patients with atherothrombotic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusive disease, the chronic reduction in cerebral perfusion pressure (chronic hemodynamic compromise) increases the risk for cerebral ischemic damage. We have shown that severe hemodynamic compromise, demonstrated as increased oxygen extraction fraction (misery perfusion) with PET, is a risk factor for subsequent ischemic stroke. We have also shown that selective neuronal damage demonstrated as a decrease in central benzodiazepine receptor in the normal-appearing cerebral cortex is associated with increased oxygen extraction fraction (misery perfusion). Detection and appropriate treatment of the patients with misery perfusion is important for preventing ischemic damage in patients with atherothrombotic ICA or MCA occlusive disease. Using PET, we have correlated CBF response to acetazolamide with hemodynamic and metabolic parameters in patients with atherothrombotic ICA or MCA occlusive disease, which suggested that evaluation of cerebral vasodilatory capacity using SPECT with acetazolamide could detect patients with hemodynamic compromise including patients with misery perfusion. A Japanese EC/IC bypass trial for patients with severe hemodynamic compromise, demonstrated as decreased CBF and decreased CBF response to acetazolamide with SPECT, showed a benefit of bypass surgery for preventing ischemic stroke. Thus, detection of the patients with severe hemodynamic compromise is crucial for improving the prognosis of patients with atherothrombotic ICA or MCA occlusive disease. Understanding the pathophysiology of hemodynamic cerebral ischemia is essential for the management of patients with atherothrombotic ICA or MCA occlusive disease. Pathophysiology of hemodynamic cerebral ischemia studied with PET has had impact on clinical significance of SPECT examinations for improving prognosis of patients.

Effect of a gonadotropin releasing hormone analog on cerebral hemodynamics in premenopausal women

Background Impaired reactivity of cerebral blood vessels is associated with increased risk of stroke. Female sex hormones have vasoactive effects in a number of vascular beds but their effects upon the cerebral circulation are not well understood. Ultrasound techniques allow us to examine the ability of intracranial vessels to dilate in response to a pharmacological stimulus (the carbonic anhydrase inhibitor acetazolamide). We studied intracranial hemodynamics in a group of premenopausal women before and after induction of a temporary hypoestrogenic state.Methods We examined middle cerebral artery mean flow velocity, common and internal carotid artery pulsatility index and cerebrovascular reactivity to acetazolamide (CVR) in a group of women undergoing treatment for menstrual disorders. Volunteers underwent ultrasound examination during the follicular phase of the menstrual cycle and after completing treatment with gonadotropin releasing hormone (GnRH, goserelin 3.6 mg) administered subcutaneously every 28 days for 12 weeks. The study was conducted in a prospective, single-blind fashion and analyzed using parametric comparisons of means to examine change in intracranial hemodynamic parameters between pre- and postmenopausal states.Results Twelve premenopausal women aged 37.2 ± 7 years and without overt vascular disease completed the protocol. GnRH reduced serum estrogen concentration (215.6 ± 122 pg/ml vs. 82.4 ± 12 pg/ml, p = 0.0047) but this was not associated with a change in CVR (145 ± 19% and 146 ± 14% for follicular and post-GnRH studies, respectively (p = 0.6). No significant changes in blood pressure, internal carotid or middle cerebral artery pulsatility or mean flow velocity were observed between time points.Conclusion Neither resting cerebral hemodynamics nor reactivity of cerebral resistance vessels to a potent vasodilatory stimulus changed when the circulating concentration of estradiol was artificially decreased using a GnRH agonist. Induction of a hypoestrogenic state does not appear to influence cerebral vasodilatory capacity in the short term.

Acetazolamide as a vasodilatory stimulus in cerebrovascular diseases and in conditions affecting the cerebral vasculature.

Pathologic processes affecting the brain vessels may damage cerebral vasodilatory capacity. Early detection of cerebral dysfunction plays an important role in the prevention of cerebrovascular diseases. In recent decades acetazolamide (AZ) has frequently been used for this purpose. In the present work the mechanism of action and the previous studies are reviewed. The authors conclude that AZ tests are useful in cerebrovascular research. Further investigations are recommended to prove how impaired reserve capacity and reactivity influence the stroke risk in patients and whether these tests may indicate therapeutic interventions.

Monitoring of Cerebral Vasodilatory Capacity With Transcranial Doppler Carbon Dioxide Inhalation in Patients With Severe Carotid Artery Disease

Cerebral vasodilatory capacity (CVC) testing with transcranial Doppler has been shown to be useful in the assessment of stroke risk in patients with symptomatic and asymptomatic internal carotid artery (ICA) stenosis and occlusion, but whether hemodynamic status improves, deteriorates, or remains the same over time is uncertain. Thirty-five patients with >or=80% carotid artery stenosis or complete occlusion underwent CVC testing at baseline and 6 months later. CVC was assessed by measuring the increase in ipsilateral middle cerebral artery mean flow velocity in response to 5% inhaled CO2. Continuous tracings of left and right middle cerebral artery flow velocity, heart rate, respiratory rate, and Pco2 were recorded and then analyzed offline. One-way analysis of variance was used to compare baseline CVC in symptomatic and asymptomatic patients with control subjects. A paired t test was used to compare CVC before and after revascularization. Also, chi2 analysis was used to compare rates of cerebrovascular events in patients with low compared with normal CVC over the 6-month period and in 14 patients whose ICAs were revascularized. Patients with high-grade stenosis or occlusion of the ICA who had ICA disease had an average CVC of 2.4+/-1.9%/mm Hg Pco2; control subjects averaged 4.2+/-1.1%/mm Hg Pco2. (P=0.01). In the revascularization group, CVC increased from an average of 1.4+/-1.7%/mm Hg Pco2 at baseline to an average of 2.8+/-1.0%/mm Hg Pco2 after revascularization, significantly different from the spontaneous change in the natural history group over 6 months (P=0.003). Over the 6-month follow-up period, in the natural history group and in the treatment group after revascularization, 4 ischemic events occurred, all in patients with abnormal CVCs; abnormal CVC was associated with ischemic events (Fisher's exact test, P=0.03). In a timeframe pertinent to clinical decision making and clinical trial outcomes, cerebral hemodynamic status may not be constant. A higher ischemic risk may be present in patients with severe carotid artery disease whose CVC is poor at baseline, becomes poor over 6 months, or fails to normalize after revascularization.

Cerebral blood flow and vasodilatory capacity in anemia secondary to chronic renal failure

Our previous study reported that cerebral oxygen extraction fraction (OEF) increased in hemodialysis patients with anemia. The increased OEF suggests that the cerebral vasodilatory capacity might be impaired in these patients. To clarify this issue, we measured the CO2 response in patients with anemia secondary to chronic renal failure (CRF) using positron emission tomography (PET). Ten anemic patients with CRF (6 females and 4 males) and 6 age-matched normal controls were studied. The underlying diseases of CRF were glomerulonephritis in 8 patients, systemic lupus erythematosus (SLE) in one patient, and hypertension in one patient; in this cohort, 5 patients were on hemodialysis treatment and the remaining 5 patients were in a pre-hemodialysis state. The cerebral blood flow (CBF) was measured by the O-15 H2O bolus injection method with each patient in a resting state and during 5% CO2 inhalation. The CO2 response was estimated as the percentage change of CBF per 1 mm Hg change of PaCO2. The CO2 response was significantly attenuated in anemic patients with CRF in comparison to the normal controls, and it inversely correlated with the severity of anemia. There was no significant difference in the CO2 response between the hemodialysis and pre-hemodialysis patients. The CO2 response significantly correlated with CBF and the cerebral metabolic rate for oxygen (CMRO2) at rest, however, it did not correlate with OEF and cerebral blood volume (CBV). The present study revealed the existence of a reduced cerebral vasodilatory capacity in anemic patients with CRF, suggesting that chronic hypoxic brain damage might play a role in the impaired cerebrovascular response to CO2.

&lt;SUP&gt;133&lt;/SUP&gt;Xe SPECTによる定量的評価に基づいた慢性期内頸動脈系閉塞性病変に対するバイパス術の効果

To evaluate the efficacy of bypass surgery, we analyzed the clinical outcome and cerebral hemodynamics of patients treated with bypass surgery.Over a 3-year period, 21 patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had one or more episodes of focal cerebral ischemia due to unilateral internal carotid or middle cerebral artery occlusion. Computerized tomography scans either were normal or showed evidence of watershed infarction. The baseline cerebral blood flow (CBF) and cerebral vasodilatory capacity (CVC) were studied using 133Xe single-photon emission CT and acetazolamide test, and both were found to be significantly reduced in all patients. Based on these criteria, superficial temporal artery-middle cerebral artery anastomosis was performed. One patient suffered a postoperative stroke with complete recovery, resulting in a morbidity rate of 4.8%. Over a mean follow-up period of 20 months, no patient had another episode of cerebral ischemia. Follow-up studies of baseline CBF and CVC showed significant improvement of the latter while the former was essentially unchanged. In view of these findings, we conclude that bypass surgery constitutes appropriate therapy for patients with hemodynamic cerebral ischemia, defined using the strict selection criteria employed in this study.

Effect of acetazolamide reactivity on [corrected] long-term outcome in patients with major cerebral artery occlusive diseases.

It remains unclear whether hemodynamic insufficiency plays a major role in ischemic events. We performed a prospective follow-up study in ischemic stroke patients with occlusive large-artery diseases to determine whether stroke recurrence is related to reduced vasodilatory capacity, judged with single-photon emission CT and acetazolamide (ACZ) challenge. During the period from 1987 to 1995, we examined cerebral vasodilatory capacity with single-photon emission CT and an ACZ challenge in 105 consecutive stroke patients with severe stenosis (> 75% in diameter) or occlusion of the internal carotid artery or the trunk of the middle cerebral artery who had no or minimal infarcts on CT. According to criteria reported earlier, the patients were divided into two groups: normal (negative ACZ, n = 50) or reduced ACZ reactivity (positive ACZ, n = 55). They were prospectively followed at regular intervals for a median period of 2.7 years. The Kaplan-Meier analysis revealed no difference in cumulative recurrence-free survival rate between the two groups. The multivariate analysis with Cox proportional hazards model demonstrated that a high systolic blood pressure at entry into the study significantly increased stroke recurrence (coefficient = .0466; hazard ratio = 1.0477; 95% confidence interval = 1.0017 to 1.0957; P = .04), whereas antihypertensive medication significantly reduced stroke recurrence (coefficient = -1.527; hazard ratio = 0.217; 95% confidence interval = 0.0612 to 0.771; P = .02), but no other variables including ACZ reactivity affected stroke recurrence rate. The present results demonstrate that reduced vasodilatory capacity does not play a major role in stroke recurrence. Antihypertensive therapy appears to reduce stroke recurrence even in patients with hemodynamically significant arterial diseases.

An approach to cerebral vasodilatory capacity in unilateral and bilateral cerebrovascular diseases using radiolabeled human serum albumin.

The acute cerebrovascular response to acetazolamide was assessed using a blood pool agent and planar dynamic imaging to evaluate cerebral vasodilatory capacity. Ten normal subjects and 12 patients with unilateral or bilateral cerebrovascular disease were studied. After the injection of radiolabeled human serum albumin, dynamic imaging of the anterior view of the head was started. Ten minutes later, 1000 mg of acetazolamide was infused. The dilatation index (the percent increase in activity at the peak response) was obtained for each cerebral hemisphere. The mean dilatation index in normal subjects was 17.1 +/- 3.2% (N = 20). The value was significantly lower in patients with multiple infarcts (7.7 +/- 1.1%, N = 8, P < 0.001), and below the normal range in two involved hemispheres of five patients with unilateral occlusive carotid artery disease and in three hemispheres of three patients with moyamoya disease. It was suggested that this simple method may be useful in assessing cerebral vasodilatory capacity in both unilateral and bilateral diseases.

Prediction of cerebral infarction due to vasospasm following aneurysmal subarachnoid haemorrhage using acetazolamide-activated 123I-IMP SPECT.

Prediction of cerebral infarction due to vasospasm (VS) following aneurysmal subarachnoid haemorrhage (SAH) was investigated using acetazolamide-activated (A-A) N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) in 79 SAH patients. A-A SPECT was undertaken twice or more for one each patient by Day 18. Fifty-six (71%) of the 79 patients presented with reduction of cerebral vasodilatory capacity (CVC) on SPECT due to VS by Day 18. Of the 56 patients, 29 showed CVC by Day 8 (Group A), while the other 27 first showed CVC reduction between Day 9 and 18 (Group B). Cerebral infarction on CT was revealed by Day 18 in 15 patients (52%) of Group A and 3 (11%) of Group B. Of the 56 patients, 20 showed reduced CVC in watershed[s] (Type 1), 12 in a sole territory of the intracranial major arterial trunk (Type 2), and 24 in several territories or in a sole territory with distant watershed[s] (Type 3). Cerebral infarction on CT by Day 18 was revealed in one patient (5%) in Type 1, 3 (25%) in Type 2, and 14 (58%) in Type 3. Twelve (71%) of 17 patients belonging to both Group A and Type 3 resulted in cerebral infarction. These results suggest that early and extensive CVC reduction are significant factors responsible for cerebral infarction due to VS following SAH. Cerebral infarction can be reasonably predicted using A-A SPECT in SAH patients.