Cerebrovascular Reserve Capacity Research Articles

Improvement of cerebrovascular reserve capacity by EC-IC arterial bypass surgery in patients with ICA occlusion and hemodynamic cerebral ischemia

Since the negative results of the international Bypass Study, extracranial-intracranial (EC-IC) bypass surgery is infrequently employed in the treatment of patients with cerebral ischemia. Newly acquired evidence concerning the pathophysiology of cerebral ischemia, however, has facilitated the identification of a small subgroup of patients with "hemodynamic" cerebral ischemia. Characteristically, these patients demonstrate severely impaired cerebrovascular reserve capacity due to occlusive disease and insufficient collateral blood supply. Over an 8-year period, 28 patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had recurring episodes of focal cerebral ischemia due to unilateral internal carotid artery occlusion. Computerized tomography (CT) scans either were normal or showed evidence of border zone infarction. The cerebrovascular reserve capacity was studied using 133Xe single-photon emission CT and acetazolamide challenge and was found to be significantly impaired in all patients. Based on these criteria, superficial temporal artery-middle cerebral artery anastomosis was performed to augment collateral flow to the ischemic hemispheres. Two patients died from myocardial infarction, one 4 days and the other 2 months postoperatively. One patient died from massive brain infarction and another suffered a postoperative stroke with incomplete recovery, resulting in a major morbidity and mortality rate of 14%. Minor morbidity included one patient with a subdural hematoma who subsequently recovered completely. The postoperative course was uneventful in 23 patients (82%). Over a mean follow-up period of almost 3 years, no patient had another episode of brain ischemia. Bypass patency was confirmed by postoperative angiography in 26 patients. Follow-up studies of cerebral blood flow (CBF) and cerebrovascular reserve capacity showed significant improvement of the latter while the resting CBF was essentially unchanged. In view of these findings, the authors conclude that EC-IC bypass surgery constitutes appropriate therapy for a subgroup of patients with recurrent focal cerebral ischemia, defined using the strict selection criteria employed in this study.

STA-MCA bypass in bilateral carotid artery occlusion: clinical results and long-term effect on cerebrovascular reserve capacity.

In this report we describe our experience with extracranial-intracranial arterial bypass surgery in a subgroup of 9 patients (mean age at surgery 61 +/- 9 years) with bilateral carotid artery occlusion, unilaterally symptomatic for occlusive cerebrovascular disease of haemodynamic origin. Haemodynamic insufficiency is characterized by a severely reduced cerebrovascular reserve capacity, measured with Xe-133 D-SPECT and acetazolamide challenge. Preoperatively, the mean baseline cerebral blood flow of 54 +/- 6 ml 100 g-1 min-1 did not change after challenge (54 +/- 5 ml 100 g-1 min-1) in the symptomatic hemisphere. Immediately following surgery an improvement in cerebrovascular reserve capacity for up to 14 +/- 8 ml 100 g-1 min-1 (1-2 years control) was noted. One patient subsequently died from a perioperative stroke, another patient died three months post-operatively from a myocardial infarction. Three patients were followed up to 4 years, four for 2 years. Patients with former transient ischaemic attacks had no further attacks, symptoms from PRIND or minor stroke did not progress further, nor did new symptoms occur. Unilateral extracranial-intracranial bypass surgery has a positive effect on clinical outcome in highly selected patients with bilateral carotid artery occlusion and cerebral ischaemia of haemodynamic origin.

Zur Hämodynamik der intrakraniellen arteriovenösen Angiome

Intracranial arteriovenous malformations (AVM) show haemodynamically two characteristics: The shunt flow and the perfusion of brain tissue surrounding AVM's. In principle, only tissue perfusion can be measured with the stable-Xe-CT method. In 1954 Murphy defined the steal phenomenon in connection with AVM's. It could therefore be concluded that the AVM shunt perfusion works at the expense of tissue perfusion. This phenomenon has been shown to be responsible for serious episodes of neurological deficits in patients with AVM's. In the present report the haemodynamic influence of the AVM's on the surrounding tissue perfusion was measured with the stable-Xe-CT method which offered high resolution with a precise anatomical correlation. A total of 58 stable-Xe-CT studies were performed on 28 patients, 16 of them postoperatively. In 14 patients not only cerebral blood flow at rest but also regional cerebrovascular reserve capacity after intravenous administration of 1 g Diamox were evaluated. Of the 28 patients, 7 had small (nidus < 4 cm), 16 medium (nidus 4-6 cm), and 5 large (nidus > 6 cm) AVM's. In small and medium AVM's we could demonstrate that blood flow at rest did not differ between both hemispheres. After AVM resection the haemodynamics on both sides were not changed. The regional cerebrovascular reactivity following Diamox administration was 20 ml/100 g/min on the side of AVM compared with 40 ml/100 g/min on the contralateral side. Although this difference was statistically significant, it was within the 95% confidence interval of the normal Diamox reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of Cerebral Vasoreactivity by SPECT and Transcranial Doppler Sonography using the Acetazolamide Test

rCBF SPECT with 99mTc-HMPAO was performed prospectively in 29 patients (3 controls and 26 stroke patients) as well as TCD studies in 20 patients (3 controls and 17 stroke patients) before and after 1 g i.v. acetazolamide. The sensitivity of rCBF SPECT increased from 62% to 77% after acetazolamide provocation in stroke patients. In patients with a reversible neurological deficit, the sensitivity under resting conditions was 50% which increased to 71%, while in cases with a permanent deficit it increased from 75% to 83%. In the evaluation of the cerebrovascular reserve capacity the results of rCBF SPECT and TCD coincided in 91% of the hemispheres. The correlation was statistically significant.

Dynamic computed tomographic imaging of regional cerebral blood flow and blood volume. A clinical pilot study.

The advent of faster computed tomography scanners has evoked considerable interest in using this technology as a more practical method of regional cerebral hemodynamic evaluation than the currently available positron emission and single-photon emission computed tomography. The theoretical concepts have been worked out and validated in the laboratory by several groups. The aim of the present study was the development of a clinically useful system. Software was developed for dynamic computed tomography-based calculation and color-coded representation of regional cerebral blood flow and blood volume. Normal values, reproducibility, and sensitivity to acetazolamide challenge were established in 13 volunteers. The method was applied to an additional three patients with internal carotid artery occlusion and known decreased vascular reserve capacity as diagnosed by transcranial Doppler ultrasonography. Normal regional cerebral blood flow was determined as 50 +/- 13 ml/100 ml per minute and normal fractional cerebral blood volume as 58 +/- 12 ml/1,000 ml (mean +/- SD). In five volunteers, two examinations were performed within 15 minutes for determination of reproducibility. Intermeasurement variability of hemispheric blood flow and blood volume was determined as +/- 23% and +/- 16%, respectively. Intravenous administration of 1 g acetazolamide resulted on the average in a 75% increase of blood flow and a 65% increase of fractional blood volume. In the patients with decreased cerebrovascular reserve capacity, baseline fractional blood volume in the ischemic hemispheres was significantly increased. Baseline regional cerebral blood flow in the ischemic territories was overestimated. Reactivity to acetazolamide of both regional blood flow and fractional blood volume was clearly reduced in the ischemic hemispheres. The present results demonstrate that the method is a simple and effective means of determining regional cerebral blood volume. Spatial resolution is superior to that of the radioactive tracer methods. Hemodynamic evaluation of ischemic conditions can be performed on the basis of increased resting cerebral blood volume and a diminished increase after acetazolamide. Accuracy of cerebral blood flow measurements, on the other hand, is affected by abnormal cerebral blood volume, and corresponding adjustments need to be made in pathological conditions.

Cerebrovascular Reactivity by Transcranial Doppler Ultrasonography in Insulin-Dependent Diabetic Patients

Cerebrovascular reserve capacity (CVRC) was investigated in 13 insulin-dependent diabetic (IDDM) patients with clinical microangiopathy and in 12 healthy subjects. CVRC was assessed by transcranial Doppler (TCD) ultrasonography continuously recording mean blood flow velocity (FV_m) of the middle cerebral artery in the resting condition and for 2 h after an i.v. injection of 1 g acetazolamide. The increase in FV_m was observed a few minutes after the injection of acetazolamide with the highest value being reached after 10 min in both IDDM patients and controls. Each single curve was significantly increased in controls and in the diabetic group (p < 0.001 by one-way Anova analysis and the Scheffé test). When comparing FV_m in IDDM patients and controls, the values of the IDDM patients were significantly lower at all times (p < 0.05). An age-dependent decline of FV_m was observed in IDDM patients at rest (p = 0.016), but not in healthy controls (NS). The absolute increase in mean blood flow velocity after 10 min was 16.7 ± 8.5 cm/s (mean ± SD) in IDDM patients and 24.1 ± 9.3 cm/s in controls (p < 0.05), while 3 out of 13 IDDM patients had a CVRC below 1 SD of the control group. The acetazolamide test and TCD ultrasonography seem to be useful methods for assessing CVRC in IDDM patients.

Cerebrovascular reserve capacity in ischemia due to occlusion of a major arterial trunk: studies by Xe-CT and the acetazolamide test.

Classifications based on clinical and radiographic criteria have proved to be inadequate predictors of the course of cerebral ischemia or its response to therapy. In this study the cerebrovascular reserve capacity (CRC) of 46 patients with symptomatic cerebrovascular ischemia was studied by stable xenon-enhanced CT (Xe-CT) combined with the acetazolamide test. Fifteen patients had internal carotid artery (ICA) occlusion, 10 had ICA stenosis, 10 had middle cerebral artery (MCA) occlusion, and 11 had MCA stenosis. In the patients with chronic cerebral ischemia due to occlusive lesions of the ICA and MCA, the CRC was reduced most in those with MCA occlusion, followed, in descending order, by those with ICA stenosis, MCA stenosis, and ICA occlusion. Our results indicate that measurement of the CRC elucidates cerebral hemodynamic factors that cannot be detected by angiography in patients with chronic cerebral ischemia and that Xe-CT combined with the acetazolamide test is useful for this purpose.

Course of carotid artery occlusions with impaired cerebrovascular reactivity.

Retrospective studies have found a close correlation between an impaired cerebrovascular reserve capacity and the incidence of hemodynamic stroke. The present study evaluates this relation prospectively. We measured the CO2 reactivity in 85 patients with internal carotid artery occlusions by transcranial Doppler sonography (Doppler CO2 test). All patients were prospectively followed for 38 +/- 15 (mean +/- SD) months. In the group with sufficient CO2 reactivity, four of 48 (8%) developed ipsilateral transient symptoms, none a stroke. In cases with diminished or exhausted cerebrovascular reserve capacity, 12 of 37 (32%) suffered an ipsilateral event (four transient ischemic attacks, eight strokes) (p less than 0.01). The Doppler CO2 test seems to be a valuable method of estimating the risk of stroke in patients with carotid artery occlusions.

海綿静脈洞部内頸動脈巨大動脈瘤に対する術前マタス-アセタゾラミド負荷血流検査の有用性

In the present study we evaluated cerebrovascular reserve capacity (CRC) during temporal occlusion of the internal carotid artery (Matas test) as a preoperative test in the selection of candidates for permanent carotid ligation from among patients with internal carotid cavernous giant aneurysms. Cerebral blood flow (CBF) during rest (resting CBF), the Matas test (Matas-CBF), and after administration of 1g of acetazolamide during the Matas test (acetazolamide-Matas-CBF) were measured using stable xenon-enhanced CT CBF technique (Xe-CT). This procedure was named as “Acetazolamide loading Matas test.”The CRC during the Matas test (Matas-CRC) was calculated as the difference between the Matas-CBF and the acetazolamide-Matas-CBF.In a case of 51-year-old male with left internal carotid cavernous giant aneurysm, CBF study showed resting CBF, Matas-CBF, and Matas-CRC within normal limits. The left internal carotid artery was surgically trapped without complication.Among patients with internal carotid cavernous giant aneurysms, those with normal Matas-CRC in the“Acetazolamide loading Matas test”were found to be good candidates for a permanent carotid ligation.

Wertigkeit des Acetazolamid-Stimulationstestes mit der99mTc-HMPAO-SPECT bei reversibler zerebrovaskulärer Insuffizienz (CVI)

Regional cerebral blood flow reduction was measured in 84 patients with CVI using 99mTc-HMPAO-SPECT. 53 patients received 1 g acetazolamide to evaluate cerebrovascular reserve capacity. Differentiating between hemispheric (87%) and vertebrobasilar ischaemia (64%) revealed markedly increased sensitivity for the provocative test with acetazolamide. In 62% of high grade but asymptomatic carotid stenoses a haemodynamic effect was demonstrated with acetazolamide and thereby the indication for surgery was supported.

The effect of EC-IC bypass surgery on resting cerebral blood flow and cerebrovascular reserve capacity studied with stable Xe-CT and acetazolamide test

Cerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) were measured by stable xenon computerized tomography (Xe-CT) and acetazolamide test in 15 patients with cerebrovascular disease before and after extracranial-intracranial (EC-IC) bypass surgery for minor stroke, reversible ischemic neurological deficit or transient ischemic attack. All had angiographically shown occlusive lesions of the major arterial trunk. In the present series, global analysis showed that the bypass did not increase the resting rCBF, but did increase the rCRC. We divided the patients into four groups according to the preoperative resting rCBF and rCRC. All 3 patients with normal resting rCBF and reduced rCRC showed postoperative improvement of rCRC. Of 6 patients with reduced CBF and reduced CRC, three had postoperative increase in resting CBF and four had increased CRC. One of two patients with reduced CBF and normal CRC showed only an increase in CRC. We propose that reduced CRC or reduced CBF with reduced CRC are criteria for selection of candidates for bypass surgery. We conclude that Xe-CT with the Diamox test is a useful and simple method for evaluating cerebral hemodynamics. Preoperative grouping with a combination of preoperative resting rCBF and preoperative rCRC is useful for predicting the effect of EC-IC bypass surgery.

Carbon dioxide reactivity and patterns of cerebral infarction in patients with carotid artery occlusion

A total of 106 patients with 112 internal carotid artery occlusions were investigated by cranial computed tomography and transcranial Doppler ultrasonography (CO2 test), giving a measure of the cerebrovascular reserve capacity. The morphological patterns of the ischaemic lesions were classified into three categories: lacunar, thromboembolic and haemodynamic infarctions. Of 29 patients with an exhausted CO2 reactivity, 19 showed a haemodynamic type of infarction, whereas of 45 cases with a normal CO2 reactivity only 2, and of 38 patients with a diminished CO2 reactivity only 3 had haemodynamically caused infarctions (P less than 0.001). The correlation between an exhausted CO2 reactivity and the presence of haemodynamic infarctions could be of value for therapy in patients with carotid artery occlusions.

A simple test to assess cerebrovascular reserve capacity using transcranial Doppler sonography and acetazolamide.

The goal of this study was the development of a simple bedside test to assess cerebrovascular reserve capacity using transcranial Doppler sonography. We studied 33 normal persons at rest and after stimulation of cerebral blood flow with 1 g acetazolamide. Their mean +/- SD increase in blood flow velocity in 54 middle cerebral arteries 10 minutes after stimulation was 24.4 +/- 9.2 cm/sec. We tried to validate the increase in blood flow velocity as cerebrovascular reserve capacity in 21 patients with obstructive carotid artery disease and symptoms of cerebral ischemia. The patients were studied using transcranial Doppler sonography and xenon-133 dynamic single-photon emission computed tomography after acetazolamide stimulation. Their increases in blood flow velocity (delta FV) and increases in cerebral blood flow (delta CBF) correlated significantly in both hemispheres (asymptomatic: Y = 0.32X + 10.65, r = 0.45, p = 0.04; symptomatic: Y = 0.36X + 2.28, r = 0.59, p = 0.004). There was no significant difference between the slopes of the regression lines. Blood flow velocity and cerebral blood flow at rest were not correlated. The increase in blood flow velocity after acetazolamide stimulation offers a simple and reliable method for assessing cerebrovascular reserve capacity.

Mapping of rCBF and cerebrovascular reserve capacity by stable xenon CT in cerebrovascular disease: Pathophysiological aspects and effects of operative therapy

In 65 patients with extracranial occlusive vascular disease treated by operation, the rCBF was investigated by Xe CT before and after microsurgical operation

Cerebral hyperemia, stroke, and transfusion in sickle cell disease.

To investigate cerebral hemodynamics in sickle cell disease (SCD), we used the 133Xenon inhalation technique of quantifying cerebral blood flow (CBF) in 67 patients. Clinical examinations and cerebral magnetic resonance imaging also were performed in all patients. Compared with age-matched healthy controls, CBF was elevated by 68% in patients, and inversely related to hematocrit. An experimental index of cerebral blood volume, pr4, was also elevated in the patients in a similar manner. Cerebral blood volume was positively correlated to CBF in SCD patients but not in controls. History of stroke and current neurologic symptoms were associated with lower flow and higher cerebral blood volume. Transfusion therapy reduced the hyperemia, the reduction being greater than expected by hematocrit elevation alone. These findings document a vasodilatory hyperemia in SCD. This dilatation may be a risk factor for ischemic distal-field infarctions, as visualized by MRI, due to a limitation of cerebrovascular reserve capacity.

Cerebrovascular reserve capacity (CRC) in carotid artery disease: a routine test in selection for surgical treatment?

An increase of arterial carbon dioxide (CO2) partial pressure induces an increase of cerebral blood flow by dilatation of the resistance vessels. By the Transcranial Doppler sonographic technique (TCD) blood flow velocity as a correlate of flow volume can be measured within the great basal intracranial arteries. We investigated 8 patients with an internal carotid artery occlusion or high-grade stenosis and 5 cerebrovascular diseased patients without extracranial stenosis. 12 healthy volunteers and patients without vascular disease served as the control group. Blood flow velocities in the middle cerebral arteries were evaluated before and after 5 minutes of breathing a 5% CO2 gas mixture. In a prestudy the end tidal pCO2 was monitored during this procedure. As a result of the close parallelity of pCO2 increase in the prestudy group we planned to standardize the CO2 reactivity tests without consideration of the individual pCO2 values. The CO2 inhalation provoked a flow velocity increase of at least 20% in the control subjects (47.1 +/- 17.3%). The vascular diseased without extracranial stenosis responded with 34.8 +/- 17.4% (minimum: 23.5%, n. s.). The CO2 reactivity in cases of occlusion or greater than 50% stenosis was significantly decreased (p less than 0.001) both when considering only the affected sides (12.4 +/- 7.5%, maximum: 20%) and when including the non affected sides (22.6 +/- 15.0%). It is concluded that the CO2 reactivity test is a simple and valid method to evaluate the cerebrovascular reserve capacity in any case of uncertainty about the benefits of surgical treatment of a carotid stenosis. In future this technique might become one fundamental argument beside others in selecting adequate treatment.

Cerebrovascular CO2 reactivity after carotid artery occlusion.

Cerebral blood flow (CBF) was measured in 39 men at normocapnia and after 5% CO2 inhalation using the xenon-133 technique. Twenty-three patients had unilateral carotid artery occlusion with no angiographic evidence of contralateral carotid artery stenosis or ophthalmic collateral flow. Eleven of these patients had undergone extracranial-intracranial (EC-IC) bypass surgery. Sixteen age-matched normal men underwent CBF measurements at normocapnia and hypercapnia to provide control data. Mean hemispheric CBF was not different between hemispheres ipsilateral and contralateral to the carotid artery occlusion either in the patients who had undergone bypass surgery or in those with carotid artery occlusion alone. Considering all patients with carotid artery occlusion, mean CO2 reactivity was decreased in the hemisphere ipsilateral to the occlusion as compared to the contralateral hemisphere in both groups. Based on data from normal individuals, a hemispheric difference in CO2 reactivity of more than 0.94%/mm Hg PaCO2 or a global CO2 reactivity of less than 0.66%/mm Hg PaCO2 was considered abnormal for an individual patient. Six of 23 patients with carotid artery occlusion (three with an EC-IC bypass) had global or hemispheric abnormalities in CO2 reactivity. Patients with impaired CO2 reactivity were not distinguishable from other patients by neurological examination, presence of transient ischemic attacks, or evidence of infarction on computerized tomography scanning. This test was safe and simple to perform and may be a useful means of detecting impaired cerebrovascular collateral reserve capacity. If impaired CO2 reactivity after carotid artery occlusion proves to be associated with a high risk of subsequent stroke, the test would provide a physiological basis for selecting a subgroup of patients who could be helped by cerebral revascularization.

Carbonic anhydrase: chemistry, physiology, and inhibition.

Carbonic anhydrase: chemistry, physiology, and inhibition.

On the theory of the indicator-dilution method for measurement of blood flow and volume.

On the theory of the indicator-dilution method for measurement of blood flow and volume.