Effect of acetazolamide on the diuretic action of furosemide was investigated in rabbits. The rates of urine flow and excretion of salts were significantly reduced when furosemide (0.5 mg/kg) was administered with acetazolamide (10 mg/kg) compared to the diuretic response of the single furosemide (0. 5 mg/kg) administration. Reduction in the fractional excretion rate of urine volume was more pronounced than the fractional excretion rate of salts. The results suggest that reduction of diuretic action on furosemide by combined administration of acetazolamide is probably due elevated urinary pH and interference in the mechanism of inhibition of chloride transport in the ascending Henle's limb.
This study was carried out to observe the effect of testosterone on carbonic anhydrase inhibiting action of acetazolamide. Carbonic anhydrase activities in the kidneys of mice were measured by Philpot and Philpot method(1936) at 30, 90 and 150 minutes after intravenous administration of saline(0.5 ml/10 g) or acetazolamide (0.25 mg/10 g) in mice pretreated with testosterone (0.1 mg/10 g). The changes in volume and pH of urine as well as those in urinary electrolytes, such as $Na^+,\;K^+\;and\;Cl^-$ were measured at 15 minutes interval for 150 minutes in the rabbit pretreated with double administrations of testosterone(10 mg/kg), 1 hour and 18 hours, prior to the administration of acetazolamide (10 mg/kg). The results were as follows: 1. Carbonic anhydrase activities in the kidneys of mice of testosterone-pretreated groups were significantly higher than those of acetazolamide-treated group at 30 minutes. No significant changes of carbonic anhydrase activities were observed in testosterone-pretreated groups compared with saline-treated groups. 2. Combined administrations of acetazolamide and testosterone exhibited higher carbonic anhydrase activity than those group of acetazolamide alone in the kidney of mice through observed period of 150 minutes. 3. There were no significant changes in the excretion rate of urine and urinary electrolytes in the group of rabbits with testosterone administerone alone. Urine volume as well as $Na^+\;and\;Cl^-$ excretion rates in the combined treated group of acetazolamide and testosterone were significantly lower than that of acetazolamide group throughout experimental period except 15 minutes after drug administration at the time transient increase was shown. 4. Generally lower $K^+$ excretion rate was observed in the combined treated group of acetazolamide and testosterone compared with the single acetazolamide-treated group and the testosterone-pretreated group shows lowest excretion rate of potassium.
This study was undertaken to investigate the influence of prostaglandin $E_1(PGE_1)$ upon the activity of carbonic anhydrase and upon the inhibitory action of acetazolamide on carbonic anhydrase. The heparinized blood was sampled by cardiac puncture from Sprague-Dawley strain rats under ether anesthesia and was hemolysed by adding distilled water 1,000 times the amount of the blood. The activity of carbonic anhydrase of 0.1 ml of the hemolysate was measured by Maren's simplified micro-method. In the first experiment, the 7 rats were used, and the activity was measured by adding 0.1 ml of various concentrations of $PGE_1$(0.5, 1.25, 2.5, 5.0, 10 and $20\;{\mu}g/ml$). In the second experiment, the 6 rats were used and the activity was measured by adding 0.1 ml of $PGE_1(5\;{\mu}g/ml)$ and 0.1 ml of acetazolamide$(6{\times}10^{-7}M/l)$ respectively or simultaneously. Obtained results were as follows: 1) The activity of carbonic anhydrase was significantly inhibited by $PGE_1$ at doses of $0.5{\sim}10\;{\mu}g/ml$, maximally at a dose of $2.5\;{\mu}g/ml$, but inhibition was no more observed at a dose of $20\;{\mu}g/ml$. 2) The activity of the acetazolamide group was significantly less than that of the control group. 3) The activity of the $PGE_1+acetazolamide$ group was significantly less than those of the $PGE_1$ group and the acetazolamide group. It is inferred from the above results that the $PGE_1$ inhibits the activity of carbonic anhydrase dose-dependently and strengthens the inhibitory effect of acetazolamide on carbonic anhydrase.
After surgical operation in patients with arteriovenous malformation (AVM), normal pressure perfusion breakthrough (NPPB) is one of the major complications. Brain perfusion SPECT with acetazolamide stress was known to be useful to evaluate the vascular reserve in several neurological and neurosurgical conditions. The authors performed acetazolamide brain perfusion SPECT in patients with AVM and compared the brain perfusion in the post-operative clinical courses. The acetazolamide brain perfusion SPECT was helpful in defining the prognosis of the patients with AVM. We describe 4 patients with AVM who had acetazolamide brain perfusion SPECT to examine the prognosis.
This study was carried out to observe the direct effect of hydrocortisone on renal function by infusing it into a renal artery. Hydrocortisone (5mg/kg) or saline (0.5 ml/kg) was infused directly into the left renal artery of the rabbit, the right kidney was left intact to serve as a control for general action of acetazolamide (10 mg/kg) or aminophylline (10 mg/kg), which was administered intravenously 30 minutes after the direct infusion of pretreated drugs (hydrocortisone or saline). The changes of urine volume, pH, urinary excretion rates of $Na^+,\;K^+\;and\;Cl^-$, and the clearances of inulin and PAH were measured at an interval of 10 minutes for half an hour after the direct infusion of hydrocortisone or saline, and for one hour after intravenous administration of acetazolamide or aminophylline. The results of the experiment were as follows: 1. Significant changes in urine volume and urinary electrolytes (excreted rates of $Na^+,\;K^+\;and\;Cl^-$) were observed in the hydrocortisone-infused group 10 minutes after the administration of acetazolamide, compared with the saline-infused group. Especially, the effect was more potent on the infused (left) side than on the contralateral (right) side. 2. Significant changes in urine volume and urinary electrolytes were also observed in all the aminophylline-treated groups, but no remarkable difference was noticed between the hydrocortisone-infused group and the saline-infused group, nor between the left and right sides. 3. No signicant changes in the clearances of inulin and PAH were in the infused (left) side of all the experimental groups, as compared with the contralateral (right) side. From the above results, it is obvious that hydrocortisone infused into a renal artery exerts diuretic action when administered in combination with acetazolamide, and the mechanism of action rests not on its hemodynamic change for renal blood flow, but on the potentiation of carbonic anhydrase inhibiting action. However, the exact mode of action remains yet to be clarified.
The sodium bicarbonate cotransporter (NBC) protein is functionally expressed in salivary glands. In this experiment, we examined the role of NBC in $HCO_3^-$ formation in human parotid gland acinar cells. Intracellular pH (pHi) was measured in 2'-7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-loaded cells. Acetazolamide (0.1 mM) and 4,4'-diisothio cyanatostilbene-2,2'-disulphonic acid (DIDS, 0.5 mM) were used as specific inhibitors of carbonic anhydrase and NBC, respectively. The degree of inhibition was assessed by measuring the pHi recovery rate (${\Delta}pHi$/min) after cell acidification using an ammonium prepulse technique. In control experiments, ${\Delta}pHi$/min was $1.40{\pm}0.06$. Treatment of cells with 0.5 mM DIDS or 0.1 mM acetazolamide significantly reduced ${\Delta}pHi$/min to $1.14{\pm}0.14$ and $0.74{\pm}0.15$, respectively. Simultaneous application of DIDS and acetazolamide further reduced ${\Delta}pHi$/min to $0.47{\pm}0.10$. Therefore, DIDS and acetazolamide reduced ${\Delta}pHi$/min by 19% and 47%, respectively, while simultaneous application of both DIDS and acetazolamide caused a reduction in ${\Delta}pHi$/min of 67%. These results suggest that in addition to carbonic anhydrase, NBC also partially contributes to $HCO_3^-$ formation in human parotid gland acinar cells.
Seo, Won-Duck;Kim, Young-Don;Hong, Dae-Young;Kim, Dae-Hyun;Choi, Gi-Hwan;Yeo, Hyung-Tae
Journal of Korean Neurosurgical Society
/
v.40
no.6
/
pp.434-440
/
2006
Objective : The purpose of this study is to examine the influence of cranioplasty on dynamics of cerebral blood flow[CBF] and cerebrovascular reserve capacity[CVRC], and to investigate the usefulness of single photon emission computed tomography [SPECT] as a prognostic factor for neurological improvement after cranioplasty. Methods : Between March 2003 and December 2005, a prospective study was performed on 24 patients who had undergone total 25 cranioplasty operations. Cerebral blood flow velocities in the middle cerebral artery[MCA] and internal carotid artery[ICA] were obtained by transcranial Doppler ultrasonography[TCD]. The CVRC was assessed by SPECT in the natural state and after stimulation with 1g of acetazolamide. Neurological improvement after cranioplasty was compared between patients who showed hyperactivity to acetazolamide-activated SPECT [Group 1, n=7] and hypoactivity to acetazolamide-activated SPECT [Group 2, n=17]. These measurements were obtained two weeks prior to and two weeks after cranioplasty. Results : The blood flow velocities at the opposite site to the cranioplasty as well as at the cranioplasty site were significantly increased [P<0.05]. Compared with Group 2, there was significant increase in CBF and neurological improvement after cranioplasty in Group 1. Conclusion : Among patients with surgical bony defects, the patients who had normal reactivity of the CVRC showed a significant increase in CBF and neurological improvement after cranioplasty. The authors suggest that CVRC measurement prior to surgery may be an important prognostic factor for neurological improvement after cranioplasty.
Purpose: This study was performed to evaluate the outcome of encephalo-duro-arterio-synangiosis (EDAS) surgery with rest/acetazolamide Tc-99m HMPAO SPECT in moyamoya disease. Materials and Methods: Rost/acetazolamide subtraction SPECT with consecutive acquisition were done before and 2 months after 21 EDAS surgeries in 18 patients. Perfusion decrease was graded visually for 14 areas of each hemisphere as 0 (normal) to 3 (defect) using 4 point scoring system. Postoperative rest perfusion or perfusion reserve was compared with preoperative ones. Results: Among 294 areas of 21 hemispheres, rest perfusion abnormality was found in 91 areas of 15 hemispheres. Decrease of perfusion reserve was found in 146 areas of 18 hemispheres. Six hemispheres having normal rest perfusion and 12 of 15 hemispheres having rest perfusion abnormality showed reserve decrease. Three having rest perfusion defect did not change after acetazolamide in preoperative SPECT. After operation, 16 patients (89%) demonstrated clinical improvement. Fifteen among 18 hemispheres (83%) with decreased reserve improved. Rest perfusion abnormality improved in 6 among the 15 hemispheres (40%). The areas having rest perfusion and/or reserve decrease improved in 87 among 146 areas (60%). Decrease of reserve, improved in 85% (68/80). However, areas without reserve decrease also improved in 29% (19/66). The better was preoperative rest perfusion in involved areas or the more decreased vascular reserve, the more improved perfusion and reserve after operation. Conclusion: We conclude that assessment of perfusion and Perfusion reserve using rest/acetazolamide brain perfusion SPECT predict the surgical outcome in patients with moyamoya disease.
Inpyeong Hwang;Chul-Ho Sohn;Keun-Hwa Jung;Eung Koo Yeon;Ji Ye Lee;Roh-Eul Yoo;Koung Mi Kang;Tae Jin Yun;Seung Hong Choi;Ji-hoon Kim
Journal of the Korean Society of Radiology
/
v.82
no.3
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pp.626-637
/
2021
Purpose To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. Materials and Methods This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020. Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. Results There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in patients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). Conclusion Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.
Purpose : Cerebral blood flow (CBF) reactivity to acetazolamide (ACZ) is useful to select patients with hemodynamic failure. However, it is still a matter of speculation that varying degrees of regional CBF increases after ACZ administration represent the severity or stage of regional hemodynamic failure as assessed by positron emission tomography (PET). We studied to elucidate whether ACZ challenge $^{123}I-IMP$ brain single photon emission tomography (SPECT) can accurately grade the seventy of regional hemodynamic failure. Materials and Methods: Eighteen patients (M: 16, F: 2, average age: 61 years) with unilateral occlusive disease of the internal carotid artery or the trunk of the middle cerebral artery (MCA). Patients undewent $^{123}I-IMP$ brain SPECT study with acetazolamide challenge and PET study was carried out within 2 weeks before and after SPECT study. Five healthy volunteers with a mean age of 48 years (range: 28-73 yr, M: 3, F: 2) underwent PET studies to determine normal values. In SPECT study, an asymmetry index (Al)-the percentage of radioactivity of region of interest (ROI) in the occlusive cerebrovascular lesion to the contralateral homologous ROI-was used for numerical evaluation of relative $^{123}I-IMP$ distribution. In PET study, regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen ($CMRO_2$) and cerebral blood volume (CBV) values were measured with $^{15}O-labeled$ gas inhalation method and the values were used for comparison with Al (Al during acetazolamide challenge-Al of basal study) on the SPECT study. ROls were classified by severity into three groups (normal, stage I and stage II). Results: Mean values of Al in areas with normal, stage I and stage II hemodynamic failure were $6.25{\pm}7.77%\;(n=107),\;-10.38{\pm}10.41%\:(n=117)\;and\;13.30{\pm}10.51%\;(n=140)$, respectively. Al significantly differed with each groups (p<0.05). Correlation between Al and CBF, OEF and CBV/CBF in hemisphere with occlusive cerebrovascular lesion was 0.20 (p<0.01), -0.28 (p<0.01) and -0.28 (p<0.01), respectively. Conclusion: We concluded that $^{123}I-IMP$ brain SPECT with acetazolamide challenge could determine the severity ad stage of regional hemodynamic failure as assessed by PET.
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