Intravenous Administration Of Acetazolamide Research Articles

Vascular function in women: when studying perimenopause is peri important.

Vascular function in women: when studying perimenopause is peri important.

Réponse tonométrique à l’acétazolamide dans le décollement de rétine

Acetazolamide reduces intraocular pressure and stimulates absorption of subretinal fluid by the retinal pigment epithelium. Recording the intraocular pressure response to systemic acetazolamide might enable an indirect evaluation of retinal pigment epithelial carbonic anhydrase. The intraocular pressure response to a standardized dose of intravenous acetazolamide (5mg/kg) was evaluated in a "case" group of 15 patients undergoing retinal detachment (RD) surgery and in a control group of 15 patients undergoing epiretinal membrane peeling. Intraocular pressure was measured with a handheld Perkins tonometer in a supine position before (t-2 min) and after the intravenous administration of acetazolamide (t+2 min, t+6 min, t+10 min and t+30 min). The mean variation of the intraocular pressure was compared between the two groups in the non-operated eye at each time point. A significant reduction of the intraocular pressure was observed in both groups at 2, 6 and 10 minutes (P<0.01) after the injection of acetazolamide (5mg/kg). The reduction was significantly lower in the group of patients who underwent retinal detachment surgery when compared with the group of patients in whom epiretinal membrane peeling had been performed. This difference remained significant up to 10 minutes (P<0.01 at t=2, 6 and 10 min). At t=30 min, the intraocular pressure reduction was comparable in both groups. The vitreous plays a fundamental role in the pathogenesis of retinal detachment via peripheral traction. However, since not all tears lead inevitably to retinal detachment, there must also be adherence factors which can prevent the latter. The response to acetazolamide differs significantly in patients undergoing retinal detachment surgery compared with patients treated with epiretinal membrane peeling. In the occurrence of retinal detachment, deficient photoreceptor adherence to the retinal pigment epithelium has been hypothesized. Further research should aim to correlate the tonometric response to acetazolamide with photoreceptor adherence.

Abstract 2941: Wide Variability of Cerebral Blood Volume Response in the Area with Impaired Cerebrovascular Reactivity to Acetazolamide due to Occlusive Carotid Artery Disease

Background and Purpose - Recent studies have suggested that hemodynamic and metabolic responses to reduced cerebral perfusion pressure (CPP) are not so simple in patients with occlusive carotid artery disease. Autoregulatory vasodilation reaches maximal and cerebral blood flow (CBF) starts to fall, when CPP critically falls beyond autoregulatory capacity. Theoretically, cerebral blood volume (CBV) is expressed as maximally elevated in the conditions that cerebrovascular reactivity (CVR) to acetazolamide (ACZ) is impaired. However, there are almost no studies that denote whether CBV is maximally elevated in the area with reduced CBF and CVR to ACZ (Kuroda’s Type 3 ischemia). Therefore, this study was aimed to investigate the CBV response to ACZ in the area with reduced CBF and CVR due to occlusive carotid artery disease. Methods- This study included totally 24 hemispheres of 20 patients with reduced CBF and CVR on 15 O-gas PET due to occlusive carotid artery disease. There were 8 men and 12 women with a mean age of 57.9 years ranging from 33 to 72 years. All of them were admitted to our hospital between 2004 and 2010. In all 20 patients, CBF, CBV, cerebral metabolic rate for oxygen (CMRO 2 ) and oxygen extraction fraction (OEF) were quantitatively measured, using 15 O-gas PET. Subsequently, ACZ was intravenously injected to determine the reactivity of CBF and CBV. Results- Both CBF and CVR were reduced in all 24 hemispheres (Type 3). Of these, OEF was elevated in 7 hemispheres (29%). Compared with normal control (3.4 ± 0.5 mL/100g), baseline CBV were significantly elevated both in elevated OEF group (5.2 ± 1.2 mL/100g) and normal OEF group (4.5 ± 0.9 mL/100g). Intravenous administration of ACZ further increased CBV in 4 of 7 hemispheres with elevated OEF and in all 17 hemispheres with normal OEF. %CBV reactivity was 9.5 ± 12% in elevated OEF group, being significantly lower than 22 ± 13% in normal OEF group (P = 0.04, un-paired t). CBV did not increase in patients with steal phenomenon after ACZ injection in elevated OEF group, but increased in normal OEF group. Conclusion- These findings strongly suggest that baseline CBV increases, but does not reach maximal in the area with reduced CBF and CVR due to occlusive carotid artery disease, indicating that CBF response to ACZ may imply more complicated mechanisms in the severe ischemic brain.

Time Course of Vascular Reactivity Using Repeated Phase-Contrast MR Angiography in Patients With Carotid Artery Stenosis

Cerebral vascular reactivity assessment is typically performed with 2 perfusion measurements before and after a vasodilatory challenge. The aim of this study was to assess the time course of the vasodilatory effect in the brain-feeding arteries after a challenge with acetazolamide in patients with a stenosis of the internal carotid artery (ICA). Twenty-one patients with a symptomatic ICA stenosis and 18 healthy control subjects underwent 2-dimensional phase-contrast MR angiography to repeatedly measure the blood flow (mL/min) in both ICAs at baseline and in 5-minute intervals for 30 minutes after intravenous administration of acetazolamide. At baseline, the blood flow was significantly lower in the stenosed ICAs of patients (155 ± 17 mL/min) than in the contralateral ICAs (237 ± 21 mL/min, P<0.05) and the ICAs of healthy control subjects (249 ± 15 mL/min, P<0.05) and remained lower throughout the time course. The maximum vasodilatory effect in the stenosed ICAs was observed after 15.3 ± 0.9 minutes, which was significantly later than in the contralateral ICAs (within 12.9 ± 0.7 minutes, P<0.05) and healthy ICAs (within 12.8 ± 0.8 minutes, P<0.05). The onset of the maximum vasodilatory effect after administration of acetazolamide is delayed in patients with a symptomatic ICA stenosis.

Vasodilatory Capacity of the Cerebral Vasculature in Patients with Carotid Artery Stenosis

Impairment of the cerebral autoregulation is an important predictor of TIA and stroke in patients with an ICA stenosis. The autoregulative status can be assessed directly by measuring the vasodilatory capacity of the cerebral arteries. The aim of our study was to investigate the vasodilatory capacity of the proximal and distal cerebral vasculature in patients with an ICA stenosis and healthy control subjects by combining MRA with an acetazolamide provocation challenge. Fourteen functionally independent patients (mean age, 67.2 ± 8.7 years) with a symptomatic ICA stenosis and 19 healthy controls (mean age, 63.1 ± 7.2 years) were included. MRA was performed before and 20 minutes after intravenous administration of acetazolamide. The vasodilatory capacity of 11 proximal and distal cerebral vessels was assessed by measuring the increase in vessel diameter after acetazolamide. In the hemisphere ipsilateral to the ICA stenosis, there was no increase in diameter after acetazolamide, whereas a significant increase was measured in the contralateral hemisphere for the A1 and A2 segments of the ACA, the pericallosal artery, and the BA. A significant diameter increase was measured in all except 1 vessel of the controls. The vasodilatory capacity was significantly lower ipsilateral to the ICA stenosis compared with the A1 segment of the ACA and the P2 segment of the PCA in the controls. MRA combined with an acetazolamide provocation challenge can measure normal and impaired vasodilatory capacity of the cerebral vasculature.

Adverse Effects of Intravenous Acetazolamide Administration for Evaluation of Cerebrovascular Reactivity Using Brain Perfusion Single-Photon Emission Computed Tomography in Patients With Major Cerebral Artery Steno-occlusive Diseases

Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography (SPECT) were prospectively investigated in 100 patients with major cerebral artery, atherosclerotic, and steno-occlusive diseases. All patients underwent two SPECT studies (with and without acetazolamide challenge) at an interval of 2 or 3 days, received a questionnaire immediately after each SPECT study, and returned the answered questionnaire within 7 days after the study. None of the 100 patients studied experienced any symptoms during the SPECT study without acetazolamide challenge. Sixty-three patients (63%) developed symptoms during the SPECT study with acetazolamide challenge, such as headache, nausea, dizziness, tinnitus, numbness of the extremities, motor weakness of the extremities, and general malaise 1-3 hours (mean 1.6 hours) after administration of acetazolamide, and these symptoms lasted for 0.5-72 hours (mean 7.9 hours). Multivariate statistical analysis revealed that younger age (95% confidence interval [CI] 0.896-0.980, p = 0.0047) and female sex (95% CI 1.178-16.129, p = 0.0274) were significantly associated with development of symptoms with acetazolamide challenge. The incidences of the development of symptoms with acetazolamide challenge were 91% (21/23) and 41% (12/29) in subgroups of women <70 years and men ≥70 years, respectively. Patients should be informed of such adverse effects of intravenous acetazolamide administration prior to the acetazolamide challenge test for evaluation of cerebrovascular reactivity.

Symptomatic Carotid Artery Stenosis: Impairment of Cerebral Autoregulation Measured at the Brain Tissue Level with Arterial Spin-labeling MR Imaging

To measure the cerebral autoregulatory status of the brain tissue supplied by the individual brain-feeding arteries in patients with symptomatic stenosis of the internal carotid artery (ICA) by using arterial spin-labeling (ASL) magnetic resonance (MR) imaging and to compare this status with that in healthy controls. Institutional review board approval and informed consent were obtained. Twenty-three patients (mean age, 69.3 years +/- 8.0 [standard deviation]) with unilateral symptomatic stenosis of the ICA and 20 healthy controls (mean age, 66.8 years +/- 6.3 [standard deviation]) underwent perfusion and flow territory-selective ASL MR imaging before and after intravenous administration of acetazolamide. Cerebrovascular reactivity was measured throughout the brain in the gray matter that is supplied by the individual ICAs and the basilar artery. Data were analyzed with paired and unpaired t tests. In patients with symptomatic stenosis of the ICA, the flow territory of the symptomatic ICA was smaller than that of the asymptomatic ICA. After administration of acetazolamide, a significant increase in cerebral blood flow at the brain tissue level was measured in both control subjects and patients in all perfusion territories. Mean cerebrovascular reactivity values were 35.9% +/- 3.0% (standard error) and 44.6% +/- 3.5% (standard error) in the flow territories of the patients with symptomatic ICAs and those with asymptomatic ICAs, respectively, and 47.9% +/- 3.1% (standard error) in the control subjects. Cerebrovascular reactivity was lower in the flow territory of the symptomatic ICA than in the arteries of control participants (mean difference, -12.0%; 95% confidence interval: -20.7%, -3.3%). In patients with symptomatic stenosis of the ICA, vasodilatory capacity in the flow territories of the major cerebral arteries can be visualized and quantified at the brain tissue level with ASL MR imaging.

Relationship Between Cerebral Vasomotor Reactivity and White Matter Lesions in Elderly Subjects Without Large Artery Occlusive Disease

The relationships between cerebral vasomotor reactivity (CVR) and white matter lesions (WMLs) were investigated mainly in patients with carotid stenosis. We aimed to study the relationship in asymptomatic elderly subjects without large artery occlusive disease. A total of 33 elderly individuals (mean age was 76.2 years) who were free from neurological deficit or cognitive impairment were studied. Bilateral mean blood flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed transcranial Doppler (TCD) system together with intravenous administration of acetazolamide as vasodilatory stimuli. WMLs on a fluid-attenuated inversion recovery (FLAIR) sequence of MRI were classified into two categories: subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH). The lesions in each category were then divided into three grades (grade 0-I, grade II, grade III) according to the Fazekas scale. CVR was inversely associated with the extent of SDWMH and PVH. The differences in CVR were statistically significant among different severity of WMLs: for SDWMH (70%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001); for PVH (80%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001). Impaired CVR is related to the extent of WMLs in asymptomatic elderly individuals without large artery stenosis. The findings in our study suggest that dysfunction of cerebral vascular autoregulation might be an important factor in the development of WMLs in the asymptomatic elderly without large artery occlusive disease.

Stevens-Johnson Syndrome Associated With Intravenous Acetazolamide Administration for Evaluation of Cerebrovascular Reactivity-Case Report-

A 62-year-old man with left middle cerebral artery stenosis manifesting as transient ischemic attack underwent evaluation of regional cerebrovascular reactivity to acetazolamide using single photon emission computed tomography. Three days after intravenous administration of acetazolamide, erythematous eruptions of various sizes appeared on his back and spread over almost his entire body. Subsequently, painful ulcerations developed on his lips, and oral and nasal mucosa, and the conjunctiva became hyperemic, indicating Stevens-Johnson syndrome. The results of the lymphocyte transformation test were positive to only acetazolamide. Stevens-Johnson syndrome, also known as erythema multiforme major, can be life-threatening, and may be induced by intravenous administration of acetazolamide.

Effect of Carbogen Breathing and Acetazolamide on Optic Disc Po2

Acetazolamide was previously shown to increase optic disc partial pressure of oxygen (PO(2)). The study was conducted to evaluate optic disc PO(2) variations during normoxia, hyperoxia (100% O(2)), and carbogen breathing (95% O(2), 5% CO(2)), before and after intravenous administration of acetazolamide. PO(2) measurements were obtained at intervascular areas of the optic disc in nine anesthetized minipigs using oxygen-sensitive microelectrodes (10-microm tip diameter) placed at <50 microm from the optic disc. PO(2) was measured continuously during 10 minutes under normoxia, hyperoxia, or carbogen breathing. Oxygen measurements were repeated under these conditions after intravenous injection of acetazolamide (500-mg bolus). In hyperoxia, optic disc PO(2) increased moderately (DeltaPO(2) = 4.81 +/- 1.16 mm Hg (mean +/- SD; 24%; P < 0.001) after a much larger increase in systemic PaO(2). Carbogen breathing induced a significant increase in both systemic PaO(2) and PaCO(2), which resulted in a large increase in optic disc PO(2) (DeltaPO(2) = 13.17 +/- 2.18 mm Hg; 67%; P < 0.001). Acetazolamide induced a slow and progressive increase in both systemic PaCO(2) and optic disc PO(2) (30 minutes DeltaPO(2) = 4.24 +/- 2.45 mm Hg; 24%; P < 0.04). However, it was when carbogen was simultaneously administered that optic disc PO(2) increased most substantially (DeltaPO(2) = 18.91 +/- 5.23 mm Hg; 90%; P < 0.002). Carbogen breathing increases optic disc Po(2) significantly in minipigs, more than hyperoxia. The association of acetazolamide injection with carbogen breathing could induce an additional increase in optic disc PO(2) through the effect of higher systemic PaCO(2).

Identification of Hemodynamic Compromise by Cerebrovascular Reserve and Oxygen Extraction Fraction in Occlusive Vascular Disease

Cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) are used to identify hemodynamic compromise in symptomatic patients with carotid occlusive vascular disease, but evidence suggests that they are not equivalent. The authors studied the relationship between CVR and OEF to evaluate their equivalence and stages of hemodynamic compromise. Symptomatic patients (N = 12) with carotid occlusion were studied by stable xenon-computed tomography CBF after intravenous acetazolamide administration for CVR, followed within 24 hours by positron emission tomography (PET) for OEF. Middle cerebral artery territories were analyzed by hemisphere and level. Hemispheric subcortical white matter infarctions were graded with magnetic resonance imaging. Both hemispheric and level analysis of CVR and OEF showed a significant (P = 0.001), negative linear relationship [CVR (%) = -1.5 (OEF) + 83.4, (r = -0.57, P = 0.001, n = 24]. However, 37.5% of the hemispheres showed compromised CVR but normal OEF and were associated (P = 0.019) with subcortical white matter infarction. CMRO2 was elevated in stage II hemodynamic compromise (CVR < 10%, OEF > 50%). CVR and OEF showed a significant negative linear relationship in stage II hemodynamic compromise but revealed hemispheres in hemodynamic compromise by CVR but normal OEF that were associated with subcortical white matter infarction.

Effect of acetazolamide on the optic disc oxygenation in miniature pigs.

The purpose of our study was to evaluate the variations of the optic disc PO (2) during normoxia and hyperoxia (100 % O (2)), before and after intravenous administration of acetazolamide. PO (2) measurements were obtained at intervascular areas of the optic disc in 11 anaesthetized miniature pigs using oxygen-sensitive microelectrodes introduced through the vitreous cavity by a micromanipulator. PO (2) was measured continuously during 10 minutes under systemic normoxia and systemic hyperoxia. Oxygen measurements were repeated under these conditions after intravenous injection of acetazolamide (bolus of 500 mg) in 8 animals. In systemic hyperoxia, the optic disc PO (2) increased moderately (DeltaPO (2) = 4.7 +/- 2.5 mmHg; p < 0.001; n = 11) in parallel with systemic PaO (2). Acetazolamide led to a slow and progressive increase in the optic disc PO (2) (DeltaPO (2) = 2.1 +/- 1.7 mmHg; p > 0.1; n = 8 after 10 min, while DeltaPO (2) = 4.3 +/- 3.2 mmHg; p < 0.05; n = 8 after 30 min), in parallel with a slow and progressive increase in systemic PaCO (2). The optic disc PO (2) increased much more significantly after injection of acetazolamide under systemic hyperoxia (DeltaPO (2) = 13.3 +/- 3.1 mmHg; p < 0.001; n = 8). Systemic hyperoxia alone is not sufficient to increase substantially the optic disc PO (2) in miniature pigs due to a vasoconstrictor effect. Intravenous injection of acetazolamide can increase the optic disc PO (2) progressively, due to a vasodilatory effect of elevated systemic PaCO (2). The association of acetazolamide injection with systemic hyperoxia can further improve the oxygenation of the optic disc.

Assessment of acetazolamide reactivity in cerebral blood flow using spectral analysis and technetium-99m hexamethylpropylene amine oxime.

Cerebral blood flow (CBF) can be quantified noninvasively using the brain perfusion index (BPI), determined from radionuclide angiographic data generated with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). Previously, the BPI has been calculated using graphical analysis (GA); however, the GA method is greatly affected by the first-pass extraction fraction and retention fraction, which are not only variable, but lower in cases with an increased CBF, such as after the administration of acetazolamide. Thus, GA-calculated BPI values (BPIG) may not reflect the absolute CBF. The objective of this study was to use the spectral analysis of radionuclide angiographic data collected using 99mTc-HMPAO to examine changes in the BPI after the administration of acetazolamide. We studied the CBF of both cerebral hemispheres in six healthy male volunteers; the BPI was measured at rest and after the intravenous administration of 1 g of acetazolamide. In all participants, an H215O positron emission tomography (PET) examination was also performed, and the spectral analysis-calculated BPI values (BPIS) and BPIG values were compared with the actual CBF measured using H215O PET (mCBFPET). The BPIS was 1.070 +/- 0.051 (mean +/- SD) at rest and 1.497 +/- 0.098 after acetazolamide; the corresponding BPIG values were 0.646 +/- 0.073 and 0.721 +/- 0.107. The BPIS values were significantly correlated with the mCBFPET values, whereas the BPIG values were not. According to the BPIS values, the increase in BPI after the intravenous administration of acetazolamide was 40.1 +/- 8.4%, as opposed to an increase of only 11.3 +/- 6.5% according to the BPIG values. These results suggest that the spectral analysis of 99mTc-HMPAO-generated data yields a more reliable BPI than GA for the quantification of CBF after acetazolamide administration.

Test‐retest reproducibility of quantitative CBF measurements using FAIR perfusion MRI and acetazolamide challenge

The reproducibility of quantitative cerebral blood flow (CBF) measurements using MRI with arterial spin labeling and acetazolamide challenge was assessed in 12 normal subjects, each undergoing the identical experimental procedure on two separate days. CBF was measured on a 1.5T scanner using a flow-sensitive alternating inversion recovery (FAIR) pulse sequence, performed both at baseline and 12 min after intravenous administration of acetazolamide. T(1) was measured in conjunction with the FAIR scan in order to calculate quantitative CBF. The CBF maps were segmented to separate gray matter (GM) from white matter (WM) for region-of-interest (ROI) analyses. Post- acetazolamide CBF values (ml/100 g/min, mean +/- SD) of 87.5 +/- 12.5 (GM) and 46.1 +/- 10.8 (WM) represented percent increases of 37.7% +/- 24.4% (GM) and 40.1% +/- 24.4% (WM). Day-to-day differences in baseline CBF were -1.7 +/- 6.9 (GM) and -1.4 +/- 4.7 (WM) or, relative to the mean CBF over both days for each subject, -2.5% +/- 11.7% (GM) and -3.8% +/- 13.6% (WM) Day- to-day differences in absolute post-ACZ CBF increase were -2.5 +/- 6.8 (GM) and 2.7 +/- 9.4 (WM) or, relative to the mean CBF increase over both days for each subject, -4.7% +/- 13.3% (GM) and 9.1% +/- 26.2% (WM). Thus, FAIR- based CBF measurements show satisfactory reproducibility from day to day, but with sufficient variation to warrant caution in interpreting longitudinal data. The hemispheric asymmetry of baseline CBF and post-acetazolamide CBF increases varied within a narrower range and should be sensitive to small changes related to disease or treatment.

Can Cerebral Vasoreactivity Predict Cerebral Tolerance to Carotid Clamping during Carotid Endarterectomy?

Cerebral vasoreactivity (CVR) was evaluated as a preoperative test in predicting cerebral tolerance to carotid clamping. A consecutive series of 115 carotid endarterectomy (CEA) cases were studied. Before surgical operation CVR was evaluated, by measuring the mean velocity of the middle cerebral artery (mv-MCA) using transcranial Doppler (TCD) at the basal condition and 20 min after intravenous administration of acetazolamide (1 g). CEA was performed under general anesthesia. TCD was used during surgery to evaluate mv-MCA and to calculate mv-MCA clamping/mv-MCA pre-clamping x100 ratio (mv-MCA%), which was used as the parameter to validate CVR. CVR did not correlate with mv-MCA% ( r = 0.22). There was no significant difference ( P= 0.09) between mean values of the non shunted subgroup and the shunted one. CVR does not seem to be suitable for evaluating cerebral tolerance to carotid clamping.

Can cerebral vasoreactivity predict cerebral tolerance to carotid clamping during carotid endarterectomy?

Cerebral vasoreactivity (CVR) was evaluated as a preoperative test in predicting cerebral tolerance to carotid clamping. A consecutive series of 115 carotid endarterectomy (CEA) cases were studied. Before surgical operation CVR was evaluated, by measuring the mean velocity of the middle cerebral artery (mv-MCA) using transcranial Doppler (TCD) at the basal condition and 20 min after intravenous administration of acetazolamide (1 g). CEA was performed under general anesthesia. TCD was used during surgery to evaluate mv-MCA and to calculate mv-MCA clamping/mv-MCA pre-clamping ×100 ratio (mv-MCA%), which was used as the parameter to validate CVR. CVR did not correlate with mv-MCA% ( r=0.22). There was no significant difference ( P=0.09) between mean values of the non shunted subgroup and the shunted one. CVR does not seem to be suitable for evaluating cerebral tolerance to carotid clamping.

Effect of familial hypertension on glomerular hemodynamics and tubulo-glomerular feedback after uninephrectomy

Familial hypertension, glomerular hemodynamic alterations, and dysregulation of tubulo-glomerular feedback (TGFB) have all been associated with the development of chronic renal failure. In the present study we evaluated renal and glomerular hemodynamics and TGFB responses in healthy kidney donors either with or without familial hypertension, before and after nephrectomy. Para-amino-hippurate plasma clearance (CPAH) and inulin plasma clearance (CInu) were measured in 15 kidney donors before and 1 year after nephrectomy. All subjects were normotensive and were kept in a sodium-replete state. Both clearances were measured after 40 min of constant infusion of PAH and Inu, as well as 20, 30, 50, and 60 min after the intravenous administration of acetazolamide (5 mg/kg). Glomerular hemodynamics were calculated by means of the Gomez formulae. Nephrectomy caused the expected decreases in CPAH and CInu and increase in the filtration fraction (all P < .0001). The decrease in renal resistances of the remaining kidney was greater at the afferent (− 24%, P = .0075) than at the efferent arteriolar level (−17%, P < .0001). The TGFB activation was not altered by nephrectomy or by familial hypertension. Effective renal plasma flow (ERPF) decrease after TGFB activation appeared earlier than glomerular filtration rate (GFR) decrease before (P = .01), but not after, nephrectomy (P = .48). The presence of familial hypertension was associated with increased glomerular pressure (P = .0004). This study suggests that uninephrectomy in healthy human subjects causes a greater decrease in afferent arteriolar resistances, but that TGFB responses are not quantitatively altered. Familial hypertension is associated with a tendency toward higher glomerular pressures.

Acetazolamide Vasoreactivity in Vascular Dementia: A Positron Emission Tomographic Study

The present study investigates the vasoreactivity of the brain in patients with large infarcts and dementia (multi-infarct dementia; MID) and in patients with microangiopathy, lacunes, white matter changes and dementia (lacunar dementia; LD) using positron emission tomography (PET) and ¹³NH₃ as regional cerebral blood flow (rCBF) tracer. In the control group, an increase in rCBF ranging from 32 to 43% was found in all brain regions after intravenous acetazolamide administration. In both the MID group and the group with multiple infarcts without dementia, moderate loss of vasoreactivity was observed in the frontal, temporal and parietal cortex compared to the control values. Vasoreactivity was severely impaired in all cerebral regions of the LD group and restricted to the thalamus in the group with lacunes and white matter changes without dementia (lacunar stroke; LS). This suggests that global loss of vasoreactivity is not a determining factor in the occurrence of MID, but might be important in LD. The present study shows that loss of the vascular reserve leading to exhausted metabolic reserve of the whole brain is one of the possible mechanisms for the occurrence of vascular dementia.

Assessment of cerebrovascular reactivity by dynamic susceptibility contrast-enhanced MR imaging

In patients with cerebrovascular disease the acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) through the investigation of the vasomotor reactivity (VMR). This latter is currently assessed with ACZ with several methods. Recently, magnetic resonance imaging (MRI) techniques have been developed that are sensitive to stimulus-induced changes in blood flow. Dynamic susceptibility contrast material-enhanced gradient-echo MRI techniques (DSC-MRI) might be an attractive tool to assess VMR. We aimed to test the ability of DSC-MRI in the assessment of VMR. Relative hemodynamic parameters rCBV, MTT, and rCBF were evaluated at baseline after the first injection of gadopentetate dimeglumine and 10 min after the intravenous administration of ACZ (1 g) with a second bolus of contrast agent. Assessment of hemodynamic parameters was performed over the whole hemisphere and also within regions of interest. The significances of the mean differences, before and after ACZ, were assessed with repeated-measures ANOVA with two within factors: laterality (right–left) and ACZ. DSC-MRI with ACZ test was performed in ten healthy controls (aged 51.4±16.2 years). The cerebral hemispheric ratio for the three parameters (cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF)) ranged between 1.01 and 1.03. The mean gray matter-to-white matter ratio for CBV, CBF and MTT were 2.44, 2.41 and 1.05, respectively. As the laterality effect was not significant, left and right hemispheric values were averaged. A significant increase of all hemodynamic parameters was observed after ACZ ( P<0.01–0.001). The same changes for CBV, CBF and MTT were observed after ACZ according to the regions of interest ( P<0.006–0.015). DSC-MRI is a non-invasive method which enables the assessment of VMR. This technique may be added to any conventional MRI in order to detect a hemodynamic impact of an ICA stenosis. Therefore, it might be useful in determining the appropriate management when the indication for surgical versus medical therapy is in question.

Brain pH responses to acetazolamide and hypercapnia in cats.

The involvement of increased brain tissue CO2 tension in acetazolamide-induced brain acidosis was investigated by comparing the brain pH response to acetazolamide with that to hypercapnia. CO2 and pH sensors were placed bilaterally into cerebral white matter to 15 mm depth in cats. Group 1 cats (n = 9) breathed spontaneously, and in situ brain tissue PCO2, and pH (PbCO2 and pHb) were measured after intravenous acetazolamide administration (20 mg/kg). Group 2 cats (n = 9) were paralyzed and ventilated mechanically, and the changes of pHb were investigated by adjusting the ventilation to maintain the same Pbco2 values as in the acetazolamide-treated group. PbCO2 changes were not significantly different between the two groups. However, pHb responses were quite different: the fall in pHb was progressive in Group 1 but transient in Group 2. Brain acidosis after acetazolamide administration is not due to the rise in brain tissue CO2 tension.