(Stroke. 1995;26:1825-1829.)
© 1995 American Heart Association, Inc.
Articles |
Time Dependency of the Acetazolamide Effect on Cerebral Hemodynamics in Patients With Chronic Occlusive Cerebral Arteries
Early Steal Phenomenon Demonstrated by [15O]H2O Positron Emission Tomography
From the Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Correspondence to Yasuo Kuwabara, MD, Department of Radiology, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-82, Japan.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose The acetazolamide effect is thought to reach a maximum at 10 to 20 minutes after administration. However, we sometimes encountered patients who showed a transient deterioration of ischemic symptoms several minutes after acetazolamide administration. We therefore considered that a steal phenomenon may occur before the acetazolamide effect reaches a maximum. We evaluated the time dependency of the acetazolamide effect on cerebral hemodynamics in patients with severe stenosis or occlusion of the unilateral internal carotid artery.
Methods The subjects consisted of 13 patients with severe stenosis or occlusion of the unilateral internal carotid artery. Regional cerebral blood flow was measured at the resting state and at 5 and 20 minutes after the intravenous administration of 1 g acetazolamide by the use of the [15O]H2O bolus-injection method and positron emission tomography. The steal phenomenon was interpreted as positive when the regional cerebral blood flow values decreased by more than 10% after the administration of acetazolamide in more than one region of interest.
Results A steal phenomenon was observed in 5 of 13 patients at 5 minutes after acetazolamide administration on the occlusive side, whereas it was observed in only 1 patient at 20 minutes. Thus, this phenomenon was observed more frequently in the early phase of the acetazolamide test. It was also observed more frequently in patients with poorly developed collateral circulation.
Conclusions Our acetazolamide [15O]H2O positron emission tomography study revealed an early steal phenomenon at 5 minutes after intravenous administration of acetazolamide, which may be a cause of the transient deterioration of ischemic symptoms during the acetazolamide test.
Key Words: acetazolamide • carotid stenosis • cerebral blood flow • tomography, emission-computed
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Acetazolamide is a cerebral vasodilator drug that can be used to evaluate the hemodynamic reserve capacity in patients with occlusive cerebral arteries.1 2 3 The acetazolamide effect is thought to reach a maximum at 10 to 20 minutes after administration.4 5 However, we have sometimes encountered patients who showed a transient deterioration of ischemic symptoms within a few minutes after receiving acetazolamide. We therefore considered that a steal phenomenon may occur before the acetazolamide effect reaches a maximum. To clarify this issue, we measured rCBF at the resting state and at 5 and 20 minutes after the administration of acetazolamide and evaluated the time dependency of the acetazolamide effect on cerebral hemodynamics in patients with chronic unilateral occlusive cerebral arteries. These results were also compared with the degree of collateral formation on angiography.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The subjects consisted of 13 patients with chronic severe stenosis or occlusion of the unilateral ICA (4 women, 9 men; age range, 46 to 75 years; mean±SD age, 61.4±7.1 years). MRI (Signa 1.5 T, GE) was performed on all 13 patients. Conventional angiography or digital subtraction angiography was performed in 11 of 13 patients. In the remaining 2 patients, MR angiography and ultrasonic angiography were performed to evaluate the vascular lesion. The angiogram of the contralateral ICA showed slight stenosis in 4 patients, an irregularity of the wall in 5 patients, and no apparent abnormality in the remaining 4 patients. Patients with an infarct measuring more than 3 cm in diameter were excluded from this study to avoid the effect on cerebral hemodynamics. The degree of collateral formation was divided into four groups based on the angiographic findings. The degree of collateral formation was judged by a neuroradiologist without any knowledge of the PET findings according to the following criteria: - (poor), no collateral formation was observed; + (fair), middle cerebral artery territory was either not visualized or slightly visualized by the leptomeningeal anastomosis through the anterior cerebral artery or posterior cerebral artery; ++ (good), middle cerebral artery territory was visualized by the leptomeningeal anastomosis but less than half of the area; and +++ (excellent), more than half of the middle cerebral artery territory was visualized. The subjects, along with their clinical features and radiological findings, are summarized in Table 1
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PET was performed with a Headtome-III device, which had a spatial resolution of 8.2 mm in full width at half maximum and simultaneously obtained five contiguous slices 15 mm apart. The subjects were placed in a supine position on the bed in a semidark room. A small cannula was placed in the femoral artery for arterial blood sampling. A transmission scan with a 68Ge/68Ga ring source was obtained for each patient for attenuation correction. The rCBF was measured by the [15O]H2O bolus-injection method6 at the resting state and 5 and 20 minutes after the administration of acetazolamide (1 g) at an interval of 15 minutes. In the [15O]H2O PET study, 740 MBq of [15O]H2O was infused as a bolus, and the scan was started when the radioactivity appeared on a monitor for the head. The data were collected for 75 seconds in each scan. Arterial blood was continuously drawn at a rate of 15 mL/min for 2 minutes, and radioactivity was recorded by a beta-ray detector system with a plastic scintillator (1.1 cm thick and 5.1 cm in diameter). This study was approved by the committee for the clinical application of cyclotron-producing radionuclides in Kyushu University Hospital, and informed consent was obtained from the patients before the PET study. The time intervals between PET and angiography were within 1 month in 7 patients and 1 to 2 months in 4 patients. In the remaining 2 patients, MR angiography and ultrasonic angiography were performed within 1 month before the PET study.
The ROIs over an area measuring 18x14 mm were established in the
frontal, temporal, parietal, and occipital cortices and the striatum,
thalamus, centrum semiovale, and cerebellum on the PET images
referring to MR images, as shown in Fig 1. The
hemispheric CBF was obtained by the ROI (numbers 11 and 12 in Fig 1)
over the cerebrum at a level of 50 mm above the orbitomeatal line. The
response to acetazolamide was expressed as the percent
change of rCBF. The steal phenomenon was interpreted as positive when
the rCBF values decreased by more than 10% after the administration of
acetazolamide in more than one ROI. Statistical
analyses were performed with the use of the paired t
test.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Arterial blood gas and blood pressure measurements at the resting state and 5 and 20 minutes after intravenous administration of acetazolamide are shown in Table 2
. There was no significant difference in the
PaCO2 level between them. The maximum
arterial blood pressure slightly increased at 20 minutes
after the intravenous administration of
acetazolamide. However, there was no significant difference
between them. Among 13 patients, one patient (patient 1) complained of
tran-sient weakness in the right hand after intravenous
acetazolamide.
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The percent increase in hemispheric CBF was compared between 5 and 20
minutes after intravenous acetazolamide in Fig 2. Hemispheric CBF increased by 23.5±22.4% (mean±SD)
and 30.6±22.8% at 5 and 20 minutes after intravenous
acetazolamide on the occlusive side and by 37.8±19.8% and
39.5±21.7% on the nonocclusive side, respectively. There was no
significant difference in percent increase in the hemispheric CBF
between 5 and 20 minutes after intravenous
acetazolamide on the nonocclusive side. However, it was
significantly lower at 5 minutes than at 20 minutes on the occlusive
side (P<.005, paired t test). Fig 3 shows the relationship of the rCBF increases in the
brain regions between 5 and 20 minutes after intravenous
acetazolamide. The percent increase in rCBF at 5 minutes
after intravenous acetazolamide was lower than
that at 20 minutes on the occlusive side. In addition, rCBF inversely
decreased in some brain regions at 5 minutes after
intravenous acetazolamide. Fig 4
shows the relationship of the rCBF ratios (ratio of occlusive to
nonocclusive side) between 5 and 20 minutes after
intravenous acetazolamide. These ratios
correlated well with each other on both the occlusive and nonocclusive
sides. However, the rCBF ratios at 5 minutes were slightly lower than
those at 20 minutes after intravenous
acetazolamide.
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A steal phenomenon was observed on 13 ROIs in 5 of 13 patients at 5
minutes after intravenous acetazolamide on the
occlusive side, whereas it was observed on 3 ROIs in only 1 patient at
20 minutes. We compared the location of ROIs with positive steal
phenomenon with the MRI (T2-weighted image) findings. In 13
ROIs with a steal phenomenon at 5 minutes after intravenous
acetazolamide, 7 ROIs were negative on MRI, 3 ROIs were set
either near the infarct or partially included the infarct, and 3 ROIs
included small white matter lesions. In the 3 ROIs with a steal
phenomenon at 20 minutes after intravenous
acetazolamide, 2 ROIs were set near the infarct or
partially included the infarct, and 1 ROI included small white matter
lesions. In Table 3, the degree of collateral formation
on angiography was compared with the presence of a steal phenomenon at
5 minutes after intravenous acetazolamide on
PET studies in 11 patients in whom either conventional or digital
subtraction angiography was performed. A steal phenomenon was observed
more frequently in patients with poorly developed collateral
circulation. However, this phenomenon was not observed in 4 patients
with excellent collateral formation. One patient who complained of a
transient weakness in the right hand after intravenous
acetazolamide showed a steal phenomenon on the rCBF image
at 5 minutes after acetazolamide.
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Fig 5 shows the MRI, response map to
acetazolamide, and rCBF images of a 55-year-old man
(patient 11) with a complete occlusion of the left ICA at the resting
state and at 5 and 20 minutes after intravenous
acetazolamide. MRI demonstrated a small infarct (1x1 cm)
in the left basal ganglia. The development of the collateral
circulation was fair on an angiogram. The CBF image at both 5 and 20
minutes after acetazolamide showed a marked increase in the
hemispheric blood flow on the nonocclusive side, while the
cerebrovascular response to acetazolamide was severely
impaired on the occlusive side. In addition, rCBF was decreased in the
left frontotemporal region at 5 minutes after
acetazolamide, which indicated the presence of an early
steal phenomenon. However, no steal phenomenon was observed at 20
minutes after acetazolamide. The response map to
acetazolamide (areas with >10% rCBF decrease) clearly
visualized an area with a steal phenomenon at 5 minutes after
intravenous acetazolamide.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Several studies have shown that acetazolamide increases CBF by 30% to 40% after the administration of 1 g of acetazolamide.1 2 7 The effect is time dependent and appears within 2 minutes after intravenous administration.4 It reaches 80% of the maximum at 3 minutes,5 attains a maximum level at 10 minutes, and then persists for more than 30 minutes after intravenous administration.4 According to a functional MRI study based on cerebral blood oxygenation,8 the acetazolamide effect appears within 1 minute after administration, reaches a plateau at 5 minutes, and persists for more than 30 minutes. However, these studies were done in either normal volunteers or patients in whom regulation of the cerebral circulation was considered normal. There have been few reports on time dependency in patients with occlusive cerebral arteries. Recently, Hayashida et al9 measured the cerebrovascular response to acetazolamide at the resting state and 10, 20, and 30 minutes after the administration of acetazolamide 1 g IV using [15O]H2O PET in patients with ICA occlusion or stenosis and reported that a maximum response was obtained 10 minutes after the administration of acetazolamide on both sides; thus, 10 minutes was determined to be the most suitable for CBF measurement.
We measured rCBF at the resting state and 5 and 20 minutes after the
administration of acetazolamide using
[15O]H2O PET. As shown in Fig 2
, the percent
increase of hemispheric CBF did not differ between 5 and 20 minutes
after the administration of acetazolamide on the
nonocclusive side. This suggests that the acetazolamide
effect reaches a maximum within 5 minutes after intravenous
administration on the nonocclusive side; these findings closely
correlate with previous reports.5 8 10 On the other hand,
the percent increase in hemispheric CBF at 5 minutes was lower than
that at 20 minutes after intravenous
acetazolamide on the occlusive side. Thus, the time of the
appearance of the acetazolamide effect was delayed on the
occlusive side. Furthermore, a regional estimation revealed a decrease
in rCBF in some areas on the ipsilateral side, or a steal
phenomenon.
It is well known that a steal phenomenon sometimes occurs after the
administration of cerebral vasodilator drugs. Vorstrup et
al1 observed a steal phenomenon in 2 of 9 patients with
ICA occlusion at 20 minutes after the administration of
acetazolamide on 133Xe single-photon
emission CT. In our study a steal phenomenon was observed in 5 of 13
patients at 5 minutes, whereas it was only seen in 1 at 20 minutes. The
frequency of this phenomenon at 5 minutes was apparently higher than
that at 20 minutes after intravenous
acetazolamide, which suggests that a steal phenomenon
occurs more frequently in the early phase of the
acetazolamide test. As noted in "Results," 7 of 13
ROIs with a steal phenomenon at 5 minutes after
acetazolamide were negative on MRI, 2 of 3 ROIs with a
steal phenomenon at 20 minutes after acetazolamide were
either near the infarct or partially included the infarct, and the
remaining ROI included small white matter lesions. Thus, this
phenomenon can occur in an area without infarct at 5 minutes.
However, the occurrence of this phenomenon at 20 minutes is considered
to be closely correlated with infarct. Although the mechanism of the
acetazolamide effect is still not fully understood, the
effect is dose dependent4 11 and based on the inhibition
of carbonic anhydrase converting CO2+H2O to
H++HCO3- in the red blood
cell4 10 12 13 (the metabolites of glucose). Thus, the
early steal phenomenon can be explained by the lower drug delivery and
lower glucose metabolism on the occlusive side compared
with the nonocclusive side. In addition, the response to
acetazolamide on the nonocclusive side may be related to
that on the occlusive side, ie, the steal phenomenon may occur in
combination with the reduced and delayed response to
acetazolamide on the occlusive side and a good response on
the nonocclusive side. Our results also suggest that an early steal
phenomenon may be an indicator of the severity of the vascular lesions
since it was observed more frequently in patients with poorly developed
collateral circulation, as shown in Table 3.
Our acetazolamide [15O]H2O PET study revealed the presence of an early steal phenomenon at 5 minutes after intravenous acetazolamide, which was not as prominent at 20 minutes. This may therefore be a cause of the transient deterioration of ischemic symptoms sometimes observed during the acetazolamide test. In experiments using cats, Regli et al14 suggested that acetazolamide was harmful to the ischemic brain because vasodilatation and increased intracranial pressure in the nonischemic brain decreased CBF in the ischemic brain. The potential presence of this phenomenon should therefore be considered when CBF studies using acetazolamide are performed, especially in patients with poorly developed collateral circulation.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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We would like to thank Toshimitsu Fukumura, MS, for the production of [15O]H2O and Akira Mizushima, MD, for analysis of the angiograms.
Received May 15, 1995; revision received July 3, 1995; accepted July 20, 1995.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Gotoh F, Meyer JS, Tomita M. Carbonic anhydrase
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