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PubMed1984

Urothelial lesions in mice given 4-ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide, and oxamide.

4-Ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide and oxamide were administered in the diet to female BALB/c mice for varying periods of time from three to eighty weeks. All three compounds induced lesions in the urothelium. In the bladder, these included simple hyperplasia, nodular hyperplasia, inflammation and calculi. Similar lesions were observed in the ureter and urethra, along with a novel lesion, diverticulum, in the ureter. The diverticular lesions existed as down-growths of the transitional epithelium which often extended from the mucosa through the muscle layers to the adventitial surface. The etiology of the lesions appeared to be related to urinary physiological alterations (crystalluria, calculi, hypoosmolality) caused by administration of the compounds.

Acetazolamide↗
PubMed1983

The impact of acetazolamide on renal ammoniagenesis and gluconeogenesis.

In view of recent reports suggesting that acetazolamide (ACZ) inhibits renal ammoniagenesis and the pentose phosphate pathway, its effects on renal metabolism were investigated with rat isolated perfused kidney and isolated cortical tubules. In the isolated kidney perfused with glutamine (2 mM) and glucose (5mM), ACZ (0.1 mM) resulted in a natriuresis and bicarbonate diuresis and decreased NH3 production from 1.72 to 1.35 mumol/min/gm dry weight (p less than 0.05). NH3 production was unchanged in control perfusions in which no inhibitor was added. With kidneys from acidotic animals perfused with glutamine (2 mM) without glucose, NH3 production was unaltered by ACZ but glucose production decreased from 0.93 to 0.20 mumol/min/gm (p less than 0.01). ACZ inhibited NH3 (14.2 to 12.6 mumol/min/gm, p less than 0.01) and glucose (1.6 to 1.2 mumol/min/gm, p less than 0.05) and stimulated glutamate (2.2 to 2.9 mumol/min/gm, p less than 0.01) production by isolated tubules from normal rats incubated with 2 mM glutamine and had similar effects with acidotic animals. Glucose production from malate was also inhibited. The increase in glutamate and decrease in glucose production from glutamine, as well as malate, suggest that ACZ inhibits ammoniagenesis by altering metabolism of the glutamate carbon skeleton rather than by affecting glutamyl transferase. Finally, these results emphasize that ACZ has definite effects on renal metabolism, which must be considered in interpreting studies using it to elucidate hydrogen ion transport.

Acetazolamide↗
PubMed1984

Effect of arginine vasopressin, acetazolamide, and angiotensin II on CSF pressure at simulated altitude.

To test the hypothesis that arginine vasopressin (AVP) in the cerebral spinal fluid (CSF) influences CSF dynamics at simulated altitudes, cannulae were bilaterally implanted into the lateral ventricles of rabbits and rats. Recordings of CSF pressures at ambient and at various reduced barometric pressures identified an increase in CSF pressure in animals at simulated altitudes. Samples of CSF collected before and immediately after altitude exposures and assayed for AVP did not show a significant change in AVP concentration. Brain water content did not change after 6-8 h of reduced barometric pressure. Intraarterial injections of acetazolamide reduced CSF pressures, whereas intraventricular injection had no effect. Intraventricular angiotensin II (AII) elevated CSF pressures both at ambient (744-755 mm Hg) and reduced barometric pressures. When AII was preceded by saralasin, an AII blocker, the rise in CSF pressure with AII injection was prevented. Indeed, saralasin given alone, reduced or prevented the rise in CSF pressure seen at simulated altitudes. Intraventricular AVP did not influence CSF pressures nor did prostaglandins E2 and F1 alpha and norepinephrine. In AVP-deficient (Brattleboro) rats, response to intraventricular AVP depended on barometric pressure; i.e. CSF pressure rose when the rat was exposed to reduced barometric pressures and fell when the rat was exposed to ambient pressure. We suggest that hypobaric stress could cause an increase in AII content of the central nervous system which, in turn, would lead to an increase in CSF pressure. The exact mechanism of CSF pressure increase after AII increase remains to be investigated.

Acetazolamide↗
PubMed1980

Effects of acetazolamide on insulin release, serum glucose and insulin, glucose tolerance, and alloxan sensitivity of mice.

Isolated pancreatic islets exposed to 100 mM acetazolamide (AZM) and low glucose concentration exhibited increased insulin release, whereas those subjected to AZM and high glucose concentration exhibited decreased secretion of insulin. A slight transient hyperglycaemia was found 24 h after administration of 1.5 g/kg b.wt. of AZM to fed mice, whereas no such response was seen in starved mice. The serum insulin concentration was increased in the 24 h after AZM injection. Pretreatment with AZM caused decreased glucose tolerance and protection against alloxan toxicity. Inhibited carbonic anhydrase activity and ionic alterations might have played a role in the development of these effects of AZM in mice.

Acetazolamide↗
PubMed1981

[Effect of ethanol, acetazolamide, and cyclophosphamide on protein and lecithin concentrations in broncho-alveolar liquid film of mice].

An original approach to reveal in Mice, the impact of some xenobiotics and drugs on the alveolo-capillary barrier...(ethanol, acetazolamide, cyclophosphamide is described. Drugs are injected I.P. during five days in subacute dose size. Concentrations of lecithines and proteins are settled in bronchoalveolar lavage fluids from animals having or not undergone an important blood loss just before the lavage.

Acetazolamide↗
PubMed1981

Hypokalaemic periodic paralysis unresponsive to acetazolamide.

The cases of a 14-year-old farm labourer is presented as a further example of nonacetazolamide responsive hypokalaemic periodic paralysis. The family history was negative, the clinical picture classical, with prompt reversal of symptoms after the use of potassium salts. However, the administration of acetazolamide led to precipitation of an attack within a few days. The use of triamterene 100mg daily resulted in complete cessation of the attacks for the last 12 months with the maintenance of normal serum potassium levels without the use of supplementary potassium.

Acetazolamide↗
PubMed1994

Effects of chlormadinone acetate, acetazolamide and oxygen on awake and asleep gas exchange in patients with chronic obstructive pulmonary disease (COPD).

The purpose of this study was to assess the short-term effects of chlormadinone acetate (CMA), a synthetic progestogen, acetazolamide (ACET) and oxygen on awake and asleep blood gas values. The study was conducted according to a randomized, double-blind and placebo-controlled design in 53 hypoxaemic patients with chronic obstructive pulmonary disease. On the first two consecutive nights, all patients received either room air or oxygen, via a nasal cannula, in random order. They then received either CMA (25 mg), ACET (250 mg) or placebo twice a day, all in identical capsules. On the third study night, after one week of drug treatment, the patients were tested breathing room air. CMA and ACET therapy decreased mean daytime arterial carbon dioxide tension (PaCO2) by 0.7 and 0.5 kPa, respectively, and night-time end-tidal carbon dioxide tension (PETCO2) by 0.5 and 0.3 kPa, respectively. Supplemental oxygen caused increased CO2 retention during the day and night (0.6 and 0.3 kPa, respectively. Daytime arterial oxygen tension (PaO2) increased to the same extent during ACET (1.9 kPa) and oxygen (2.5 kPa). Asleep oxygen saturation improved most with oxygen supplementation (7%), although ACET also caused significant improvement (4%). CMA administration had virtually no effect on mean awake and asleep hypoxaemia. ACET therapy significantly improved subjective sleep quality. On CMA, minute ventilation increased in association with an augmentation of the hypercapnic ventilatory response. ACET treatment increased both hypercapnic and hypoxic ventilatory responses. We conclude from the group of patients with COPD studied, that the short-term effects of ACET treatment on gas exchange compare favourably with those of CMA. Oxygen therapy improves oxygenation slightly more than ACET, but aggravates CO2 retention.

Acetazolamide↗
PubMed1995

[Vasoreactivity of normal brain tissue in cases of arteriovenous malformations--evaluation by 123I-IMP SPECT using acetazolamide].

Arteriovenous malformations (AVMs) are usually associated with diminished cerebral blood flow (CBF) in the parenchyma surrounding AVMs because of the steal phenomenon. Vasoreactivity in the parenchyma surrounding AVMs may change because of ischemia and abnormal hemodynamics. The aim of this study was to investigate vasoreactivity in parenchyma surrounding AVMs. Quantitative single-photon emission computed tomography using N-isopropyl-p-I-123 iodoamphetamine (IMP-SPECT) was performed before and after intravenous administration of acetazolamide (Diamox). Diamox is a potent cerebral vasodilator which causes tissue acidosis, and IMP-SPECT was performed 10 min after intravenous infusion of a 1g dose. The subjects were 8 patients with AVMs. The AVM was in the frontal lobe in 3 patients, the temporal lobe in 1 patient, the lateral ventricle in 1 patient, the midbrain in 1 patient, the basal ganglionic region in 1 patient, and the vein of Galen in 1 patient. A rotating gamma camera with two heads was used to perform SPECT. IMP was injected into an arm vein, and a 5-min period of blood withdrawal, 1 ml/min, was started simultaneously from a small catheter placed in the radial artery. Kuhl's method was used to quantify cerebral blood flow (CBF). Multiple contiguous 6-pixel-diameter region of interest (ROI) circles along the cerebral cortex and cerebellar hemisphere were used, and ROIs which included the AVM nidus, draining veins or infarctions were excluded from the study. Vascular territories containing arteries feeding the AVM were defined as near-ROIs on SPECT, and all other ROIs were defined as far-ROIs. (ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1995

The influence of protein binding on the elimination of acetazolamide by the isolated perfused rat kidney: evidence of albumin-mediated tubular secretion.

The impact of albumin on the renal elimination of acetazolamide, a low extraction ratio compound, was investigated in the isolated perfused rat kidney. Perfusion studies were conducted over a wide range of protein concentrations (0.25, 0.5, 0.75, 1.0, 4.0 and 6.0 g/100 ml) and an initial drug concentration of 100 micrograms/ml. Kidney viability was within normal limits among all treatment groups. Over the range of albumin levels studied, an approximate 3.4-fold increase in drug-free fraction effected a 2.8-fold increase in renal clearance. Although this finding contradicted conventional wisdom regarding extraction ratio and renal elimination, the results were consistent with a proposed ancillary role of albumin in renal tubular transport processes. An alternative clearance model was developed, analogous to earlier models of hepatic elimination. The facilitated renal clearance model utilized and validated in this investigation represents a composite of previously proposed theories, modified to account for albumin-mediated tubular secretion.

Acetazolamide↗
PubMed1995

[SPECT evaluation of cerebral perfusion reserve in patients with occlusive cerebrovascular diseases: evaluation with acetazolamide test and crossed cerebellar diaschisis].

In 53 patients with chronic occlusive cerebrovascular diseases, we evaluated cerebral perfusion reserve. Cerebral perfusion reserve was evaluated by the change in cerebral blood flow (CBF) at rest and the CBF after acetazolamide (Diamox) as measured by the 133Xe gas inhalation SPECT method. Crossed cerebellar diaschisis (CCD) was evaluated semiquantitatively by the count ratio of the cerebellar cortex using 99mTc-HMPAO SPECT. Thirty-two (49%) of the 65 affected lesions in 53 patients had shown a decreased response to Diamox. In the cases of decreased response to Diamox, the response improved significantly after surgery. However, CBF did not improve as much as the response. In the 40 nonaffected sides, 21 (53%) showed decreased CBF at rest but good response to Diamox. At rest, no difference of the CBF ratio (affected/contralateral nonaffected cerebral cortex) was observed between the patients with CCD (6 pts) and those without CCD (8 pts). After Diamox, however, the CBF ratio of the patients with CCD was significantly higher than that without CCD. The change of the CBF ratio before and after Diamox correlated significantly with the degree of CCD (r = -0.794, p < 0.01). Diamox was useful for evaluating the cerebral perfusion reserve to indicate surgery in patients with chronic cerebrovascular diseases. Perhaps CCD could be a useful index in the differentiation of the decreased CBF caused by reduced perfusion pressure from that caused by reduced metabolic demand because CCD had a close relationship with the cerebral perfusion reserve.

Acetazolamide↗
PubMed1993

Cerebral vasodilatory capacity mapping using technetium-99m-DTPA-HSA SPECT and acetazolamide in moyamoya disease.

A cerebral vasodilatory capacity map, consisting of a 99mTc-DTPA-HSA SPECT image obtained after acetazolamide injection minus the baseline image, was produced in a patient with moyamoya disease. The map demonstrated diminished capacity in the posterior region of the right cerebral hemisphere. Subsequently, cerebral infarction occurred in the corresponding area. This observation suggests that regions of low vasodilatory capacity identified by cerebral vasodilatory capacity mapping may be at high risk of ischemic stroke.

Acetazolamide↗
PubMed1993

Transcranial Doppler evaluation of cerebrovascular reactivity to acetazolamide in normal subjects.

Acetazolamide (AZ), the selective inhibitor of carbonic anhydrase, was proved by intravenous Xenon 133 technique to increase cerebral blood flow (CBF). In this study cerebrovascular reactivity to AZ was evaluated in 10 normal subjects by transcranial Doppler (TCD) within the middle cerebral artery (MCA), since several reports have demonstrated that velocity of cerebral blood flow is well correlated to CBF. After 1 gr AZ injection blood flow velocity markedly increased in all subjects, with a peak in both systolic and diastolic velocity 20 min after drug administration. At that time systolic velocity increased by 35% and diastolic velocity by 50% in comparison to basal values. In contrast with Xenon 133 technique which gives one measurement only for each investigation, TCD allows a continuous monitoring of haemodynamic change following AZ infusion. MCA diastolic velocity at rest was inversely related to age (r = -.804, p < 0.01); baseline diastolic velocity was inversely related to the maximum percentage increment (r = -.745 p < .05). No change in blood pressure and heart rate was observed under experimental conditions. These results, confirm the usefulness of the AZ test in the evaluation of cerebrovascular reactivity and strongly support the use of TCD technique applied to AZ in order to investigate cerebrovascular haemodynamics in normal healthy subjects and in patients at risk of cerebrovascular insufficiency.

Acetazolamide↗
PubMed1977

Self-rated moods of humans at 4300 m pretreated with placebo or acetazolamide plus staging.

Self-rated moods were determined twice daily with the Clyde Mood Scale on 35 human subjects at 200 m (baseline) during a study concerned with evaluating the efficacy of staging plus acetazolamide (treatment) for the prevention of acute mountain sickness (AMS). Mood states also were determined on all subjects at 4300 m (Pikes Peak, Co) and on 18 of these subjects at 1600 m (staging site). Mood state changes were not observed at 1600 m, but four of the six mood factors were sensitive to the 4300 m altitude. At 4300 m, all subjects, treatment and control, rated themselves as less friendly and clear thinking and more sleepy and dizzy. At 4300 m, the treatment strategy resulted in an improved mood on the friendly, sleepy, and dizzy factors. Altitude-induced changes in clear thinking were not altered by the treatment strategy.

Acetazolamide↗
PubMed1996

Concentration-dependent tubular secretion of acetazolamide and its inhibition by salicylic acid in the isolated perfused rat kidney.

An isolated perfused rat kidney (IPK) technique was used to study the effect of salicylic acid (SA) on the excretion of acetazolamide (AZ). Initial experiments were conducted in the absence of interactants at three nominal AZ concentrations (50, 100, and 250 micrograms/ml). Over the concentration range studied, AZ demonstrated net tubular secretion in the IPK. Significant decreases in excretion ratio (4.97 +/- 0.79-2.66 +/- 1.1) and secretory clearance (0.809 +/- 0.23-0.541 +/- 0.28) were observed with increasing AZ concentration, consistent with saturation of tubular secretion. Using a facilitated model for renal secretion, values of tubular transport parameters were obtained from a plot of excretion ratio vs. unbound AZ concentration: tmax = 118 +/- 29.4 micrograms/min, KM = 53.4 +/- 22.4 micrograms/ml, and tmax(A) = 6.31 +/- 2.82 micrograms/min. In the presence of SA (200 micrograms/ml), renal secretion of AZ was inhibited, as demonstrated by significant decreases in renal clearance (0.731 +/- 0.21-0.147 +/- 0.03) and excretion ratio (3.77 +/- 0.82-0.378 +/- 0.07). Although these findings were indicative of a reabsorption component to AZ excretion in the IPK that had not been previously proposed, the results were consistent with a previous investigation of concomitant administration of AZ and SA in humans (Br. J. Clin. Pharmacol. 27, 866, 1989), thereby endorsing utilization of the IPK as a screening tool for renal clearance mechanisms in humans.

Acetazolamide↗
PubMed1996

[Noninvasive regional cerebral blood flow measurements at pre- and post-acetazolamide test using 99mTc-ECD].

A technique for serial noninvasive cerebral blood flow measurements at pre- and post-acetazolamide (Diamox) test was newly developed using 99mTc-ECD without blood sampling. Baseline mean cerebral blood flow (mCBF) was measured from graphical analysis of time activity curves for brain and aortic arch obtained from radionuclide angiography by injection of 370-555 MBq 99mTc-ECD. The first SPECT study was performed immediately after intravenous administration of 1 g of Diamox, then baseline regional cerebral blood flow (rCBF) was calculated using Lassen's correction algorithm. Immediately after the stop of the first SPECT study, additional 555-740 MBq of 99mTc-ECD was administered, thereafter the second SPECT study was started. Post-Diamox SPECT images were obtained by subtraction of the first baseline images from the second images. Using Lassen's algorithm, post-Diamox mCBF was estimated from the baseline mCBF, the baseline mean SPECT counts, and post-Diamox mean SPECT counts corrected for administered dose and imaging time. Post-Diamox rCBF was obtained from the post-Diamox mCBF and the post-Diamox mean SPECT counts using Lassen's algorithm. Coefficient variation was shown 2.7% and 3.5%: mCBF and rCBF, respectively in test-retest results in six patients without Diamox administration. Nine demented patients without vascular disorders showed significant mCBF increase of 35.7% on the average by post-Diamox. In conclusion, this simplified method is practically useful for measuring CBF at pre- and post-Diamox test within short period of time without any blood sample.

Acetazolamide↗
PubMed1996

One-day protocol for cerebral perfusion reserve with acetazolamide.

UNLABELLED: A one-day protocol with a double injection of 99mTc-ECD was introduced for the assessment of cerebral perfusion reserve with acetazolamide (ACZ). The purpose of this study was to investigate the feasibility and effectiveness of this protocol. METHODS: Thirty subjects were given double injections of 99mTc-ECD (first dose 370 MBq; second dose 740 MBq) for consecutive brain perfusion studies. Serial dynamic SPECT scans (1 min x 50 frames) were performed with the first set of SPECT data obtained by totaling the data for the frames taken between 5 and 20 min, and the second by subtracting the decay and dose-corrected initial SPECT data from the sum of the data obtained between 35 and 50 min. To evaluate the feasibility and effectiveness of the procedure, 23 of the 30 subjects were injected with ACZ 14 min after the first dose. To evaluate the reproducibility, seven subjects were not given the ACZ. The washout rate (WR) was calculated for three stages (WR1 = from 6 to 14 min, WR2 = from 20 to 28 min, and WR3 = from 36 to 44 min). Regional count increase (percent increase) and the percent count difference between normal and affected side (percent difference) were also calculated. RESULTS: Values for WR1, WR2 and WR3 did not show significant differences among the stages (WR1 = -1.43% +/- 6.09%, WR2 = -0.65% +/- 6.57%, and WR3 = -1.60% +/- 4.28%; F-value = 0.33, p-value = 0.72). Reproducibility was excellent (second SPECT = 0.964 x first SPECT; r = 0.997). Mean count increase after ACZ was 21.7%. In patients with unilateral cerebrovascular disease, the percent increase after ACZ loading was significantly greater on the normal side (26.6% +/- 13.0%) than on the affected side (19.3% +/- 13.2%) (p < 0.01), resulting in a significant increase in percent difference (control: 14.3% +/- 10.7%, ACZ: 19.2% +/- 11.5%; p < 0.01). CONCLUSION: ECD washout was minimal during the first 50 min after injection and was not affected by ACZ, which supports the feasibility of this protocol. The simple procedure and short acquisition time of this method renders it clinically useful for measuring cerebral perfusion reserve.

Acetazolamide↗
PubMed1998

Combined thallium-201 myocardial with technetium-99m-HMPAO brain SPECT: myocardial ischemia induced by acetazolamide in severe coronary artery disease.

Since the perioperative mortality of coronary artery bypass surgery is high in patients with cerebrovascular disease, it is crucial to assess a cerebrovascular risk before operation. Acetazolamide (ACZ) was applied to brain SPECT to evaluate the vascular reserve, and ACZ stress brain imaging was useful for predicting perioperative cerebrovascular events. We performed 201Tl myocardial and 99mTc-hexamethyl-propyleneamine oxime (HMPAO) brain SPECT with ACZ stress simultaneously to a patient with severe coronary artery disease and experienced the abnormality of 201Tl myocardial imaging with ACZ, as did that with dipyridamole. Technetium-99m-HMPAO brain SPECT showed no defect. Brain SPECT with ACZ demonstrated the region of poor coronary vascular reserve, which suggested myocardial ischemia induced by ACZ in a patient with severe coronary artery disease.

Acetazolamide↗