Mg Of Acetazolamide Research Articles

Ventilatory function and oxygen delivery at high altitude in the Himalayas

This study aimed to evaluate changes in lung function assessed by spirometry and blood gas content in healthy high-altitude sojourners during a trek in the Himalayas. A group of 19 Italian adults (11 males and 8 females, mean age 43 ± 15 years, and BMI 24.2 ± 3.7 kg/m2) were evaluated as part of a Mount Everest expedition in Nepal. Spirometry and arterial blood gas content were evaluated at baseline in Kathmandu (≈1400 m), at the Pyramid Laboratory - Observatory (peak altitude of ≈5000 m), and on return to Kathmandu 2–3 days after arrival at each site. All participants took 250 mg of acetazolamide per os once daily during the ascent. We found that arterial hemoglobin saturation, O2 and CO2 partial pressures, and the bicarbonate level all decreased (in all cases, p < 0.001 with R2 =0.70–0.90), while pHa was maintained stable at the peak altitude. Forced vital capacity (FVC) remained stable, while forced expiratory volume in 1 s (FEV1) decreased (p = 0.010, n2p =0.228), resulting in a lower FEV1/FVC ratio (p < 0.001, n2p =0.380). The best predictor for acute mountain sickness was the O2 partial pressure at the peak altitude (p = 0.004, R2 =0.39). Finger pulse oximetry overestimated peripheral saturation relative to arterial saturation. We conclude that high-altitude hypoxia alters the respiratory function and the oxygen saturation of the arterial blood hemoglobin. Additionally, air rarefaction and temperature reduction, favoring hypoxic bronchoconstriction, could affect respiration. Pulse oximetry seems not enough to assist medical decisions at high altitudes.

Glaucoma Drainage Device (GDD) Implantation in Post Trabeculectomy Patients

Objective: This study aims to report a case of Glaucoma Drainage Device (GDD) implant surgery in a patient who experienced an increase in Intraocular Pressure (IOP) after long term trabeculectomy. Case Presentation: A 58-year-old male patient came with complaint of blurred vision since two years ago. Patient did not complain of sore and red eyes. He was given 2 x 250 mg of Acetazolamide, 2 x 1 tablet of Aspar K, 2 x 1 right and left eye (RLE) of Latanoprost, and 2 x 1 RLE of Betaxolol HCl. The patient had glaucoma since 20 years ago and had undergone surgery in 2002 on the right eye and left eye surgery in 2004. His right eye intraocular pressure was 38 mmHg with conjungtival bleb (+) flat (+) minimal vascularity (+) horizontal extent 1-2 clock hours. Patient then underwent a GDD implant surgery on the right eye, IOP 8 mmHg post GDD. Three months after surgery, the visual acuity decrease into 6/120 ph 6/21, elevated IOP into 32 with prominent lens opacity, so the phacoemulsification was done to the right eye After the surgery, patient’s intraocular pressure was stable with better visual acuity. Conclusion: In trabeculectomy failure, implantation of the GDD is the safest and most effective option in eyes that have undergone previous intraocular surgery.

Evaluating the Effect of Acetazolamide on the Prevention of Post-operative Acute Kidney Injury after Coronary Artery Bypass Grafting Surgery: A Randomized, Open-labeled Clinical Trial.

Acute kidney injury (AKI) is a common complication after coronary artery bypass grafting (CABG) surgery and can be linked to the increased morbidity and mortality. Therefore, in the present study, the effect of preoperative administration of acetazolamide was evaluated to investigate whether it could prevent occurrence of post-operative AKI after CABG surgery. In this randomized controlled clinical trial, 130 patients who were candidates to undergo elective CABG surgery from January 21, 2020 to February 8, 2021 were randomly allocated to intervention group (receiving 500 mg of acetazolamide orally 2 h preoperatively) and control group. The patients were evaluated for AKI based on the kidney disease- improving global outcomes (KDIGO) criteria based on their serum creatinine (SCr) level and urine output until 7 days postoperatively. There was no significant difference in baseline demographics between the two groups. The total incidence of AKI was measured as 43%. Analysis of post-operative AKI incidence showed no statistically significant difference between the two groups (P = 0.860). Mean post-operative SCr level on day 1 was significantly higher in the acetazolamide group (P = 0.036). A significant difference was found in length of hospitalization stay between the groups, which was higher in the control group (P = 0.006). Our results did not demonstrate a significant protective effect of acetazolamide on incidence of post-operative AKI in the patients undergone elective on-pump CABG surgery.

ACETAZOLAMIDE FOR THE TREATMENT OF CHRONIC MOUNTAIN SICKNESS (MONGE DISEASE): A SYSTEMATIC REVIEW AND META-ANALYSIS

SESSION TITLE: Occupational and Environmental Lung Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Chronic mountain sickness is a clinical syndrome that occurs in high altitude dwellers (>2500 m) characterized by excessive erythrocytosis and severe hypoxemia. It is frequently associated with moderate to severe pulmonary hypertension, which might evolve into Cor pulmonale. Leon-Velarde et al. estimated that 5 - 10% of the 140 million living above 2500 meters are at risk of developing this disease. Qinghai Score is used to assess the severity of the disease based on the presence or absence of erythrocytosis and specific sets of signs and symptoms. Acetazolamide has been suggested as a treatment option in reducing hematocrit and erythropoietin levels. We conducted a systematic review and meta-analysis to determine if Acetazolamide provides any significant benefit over placebo for the treatment of Monge's disease. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane databases from inception through January-2020 for studies comparing daily 250 mg of Acetazolamide and placebo in the treatment of Monge's disease using terms “ Acetazolamide,” “ Chronic Mountain Sickness,” and “ Monge's disease.” Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The size of overall intervention effect was estimated by calculating the weighted average of the differences in means (DM) between the groups in each study. The random-effects model was used for all variables, and publication bias was assessed using Egger's test. RESULTS: Three randomized controlled trials published between 2005 and 2017, examining a total of 116 patients, were included in our analysis. We found Acetazolamide to be effective in reducing hematocrit DM=1.05 (0.48-1.616) (I²= 43.86%) and increasing arterial oxygen pressure (Po2 ) DM=0.91(0.51-1.31) (I²=0.00%) compared to placebo. Also, we found acetazolamide to be superior to placebo in decreasing both arterial carbon dioxide pressure (Pco2) DM=1.05 (0.65-1.46) (I²= 0.00%) and bicarbonate concentration (HCO3) DM=1.05 (0.48 -1.62) (I²= 44.21%). No significant difference in the improvement of the Qinghai Score was found between the two groups DM=-0.33 (-1.68-1.02) (I²= 90.36%). CONCLUSIONS: Our results suggest that Acetazolamide is effective in reducing erythrocytosis and improving oxygenation in patients with Monge's disease, probably by reducing hypoxic pulmonary vascular constriction (Swenson 2006) , although, no significant difference in the improvement of Qinghai Score was noticed between the two groups. CLINICAL IMPLICATIONS: Acetazolamide might be an effective treatment for chronic mountain sickness (Monge's disease). DISCLOSURES: Consultant relationship with Medtronics/Covidien Please note: $1-$1000 Added 03/28/2020 by Wael El Minaoui, source=Web Response, value=Consulting fee No relevant relationships by Ibrahim Haddad, source=Web Response No relevant relationships by Sajin Karakattu, source=Web Response No relevant relationships by Rasheed Musa, source=Web Response No relevant relationships by Todd Pearson, source=Web Response

Influence of Acetazolamide on Hand Strength and Manual Dexterity During a 30-h Simulated High Altitude Exposure.

High altitude missions pose significant challenges to Warfighter medical readiness and performance. Decreased circulating oxygen levels cause a decrease in exercise performance and can cause debilitating symptoms associated with acute mountain sickness, especially with rapid ascent. Acetazolamide (AZ) is known to minimize symptoms of acute mountain sickness, but it is unknown whether this medication alters hand strength and manual dexterity during altitude exposure. Ten male volunteers (22±4yr, 75.9±13.7kg, 174.9±9.3cm) participated in two separate 30h simulated altitude exposures (496mmHg, equivalent to 3,500m, 20°C, 20% RH) in a hypobaric chamber. Participants were given either a placebo or 250mg of AZ twice daily for 3.5d (2 sea-level [SL] days + the 30h altitude exposure) in a randomized, single-blind, crossover design. During SL and both altitude (ALT) exposures, hand function tests were performed, including hand grip and finger pinch strength tests, as well as the Purdue Pegboard (PP) and magazine loading tests to assess manual dexterity. Paired T tests and two-way repeated measure analysis of variance were used as appropriate to evaluate the effects of AZ and ALT. The value of p<0.05 was accepted for statistical significance. There were no influences of acute ALT exposure or AZ treatment on hand strength (eg, grip strength; SL: 39.2±5.5kg vs. ALT: 41.5±6.9kg, p>0.05) or dexterity (eg, PPassembly; placebo: 35.5±5.3 vs. AZ: 34.3±4.6, p>0.05) in our volunteers. Two dexterity tests (PPsum and magazine loading) showed improvements over time at ALT, regardless of treatment, where scores were improved after 10h of exposure compared to at 1h (eg, magazine loading: 56±12 vs. 48±10, p<0.001). This pattern was not seen in the PPassembly test or any strength measurements. Our results suggest that 500mg/d of AZ does not influence hand strength or manual dexterity during a 30h exposure to 3,500m simulated ALT. Acute ALT exposure (1h) did not influence dexterity or strength, although some measures of dexterity showed improvements as exposure time increased. We conclude that use of AZ to optimize medical readiness at ALT is unlikely to impair the Warfighter's ability to complete mission tasks that depend on hand function.

Remifentanil-Induced Secondary Hyperalgesia Is Not Prevented By Preoperative Acetazolamide Administration In Patients Undergoing Total Thyroidectomy: A Randomized Controlled Trial.

PurposeAcute administration of remifentanil may lead to opioid-induced hyperalgesia (OIH). Studies in mice suggest that OIH is mediated by impaired anionic homeostasis in spinal lamina I neurons due to a down-regulation of the K+-Cl− co-transporter KCC2, which was reverted using acetazolamide (ACTZ), a carbonic anhydrase inhibitor. We propose that ACTZ prevents remifentanil-mediated OIH in humans.Patients and methodsWe conducted a randomized, double-blind, placebo-controlled clinical trial between December 2016 and September 2018. Patients were randomly allocated to receive ACTZ (250 mg of ACTZ 2 h before surgery) or placebo. To detect hyperalgesia, mechanical pain threshold (MPT) were measured before and after surgery using hand-held von Frey filaments in the forearm. Anesthesia was maintained with remifentanil at a target effect site of 4.5 ± 0.5 ng/mL, and sevoflurane at an end-tidal concentration of 0.8 MAC corrected for age.ResultsIn total, 47 patients completed the study. Both groups were comparable in the baseline characteristics and intraoperative variables. Baseline MPT were similar in both groups. However, MPT in the forearm significantly diminished in the time in both groups. Finally, postoperative pain and morphine consumption were similar between groups.ConclusionBoth groups developed remifentanil-mediated OIH at 12–18 h after surgery. However, ACTZ did not prevent the MPT reduction in patients undergoing total thyroidectomy.

Acetazolamide and Hydrochlorothiazide Followed by Furosemide Versus Furosemide and Hydrochlorothiazide Followed by Furosemide for the Treatment of Adults With Nephrotic Edema: A Randomized Trial

Nephrotic edema is considered refractory if it does not respond to maximum or near-maximum doses of loop diuretics. This condition can be treated with loop diuretics and thiazides. However, animal studies show that the simultaneous downregulation of pendrin with acetazolamide and inhibition of the sodium-chloride cotransporter with hydrochlorothiazide generates significant diuresis, and furosemide administration following a pendrin inhibitor potentiates furosemide's diuretic effect. Therefore, we performed this study to compare the efficacy of acetazolamide and hydrochlorothiazide followed by furosemide versus furosemide and hydrochlorothiazide followed by furosemide for treatment of refractory nephrotic edema. Randomized, double-blind, 2-arm, parallel trial. 20 patients with refractory nephrotic edema despite treatment with 80mg of furosemide daily and creatinine clearance > 60mL/min. Patients were randomly assigned to 2 groups: group 1 (n=10) received 250mg of acetazolamide and 50mg of hydrochlorothiazide daily and group 2 (n=10) received 40mg of furosemide and 50mg of hydrochlorothiazide daily for 1 week in phase 1. In phase 2, both groups received 40mg of furosemide daily for 2 weeks. The primary outcome was absolute change in weight before and at the end of each phase. Weight and 24-hour urine volume at baseline and the end of each phase. The mean weight decrease was of significantly larger magnitude in group 1 compared with group 2 at the end of phase 1 (-1.4±0.52 [SD] vs-0.65±0.41kg; P=0.001) and phase 2 (-1.6±0.84 vs-0.5±0.47kg; P=0.005). The increase in 24-hour urine volume was also significantly higher in group 1 at the end of phase2. Small sample size, short follow-up duration, and lack of serum bicarbonate and chloride measurement. Acetazolamide and hydrochlorothiazide followed by furosemide is more effective than furosemide and hydrochlorothiazide followed by furosemide for the treatment of refractory nephrotic edema.

Acetazolamide reduces postoperative pain following laparoscopic inguinal herniorrhaphy.

Carbonic acid accumulation, which results from CO2 insufflation, can produce visceral and referred pain in the postoperative setting. Acetazolamide inhibits carbonic anhydrase, an enzyme that accelerates carbonic acid formation. We hypothesized that preoperative administration of acetazolamide would decrease postoperative pain in patients undergoing laparoscopic inguinal herniorrhaphy. A retrospective review was conducted of patients who underwent laparoscopic preperitoneal inguinal herniorrhaphy at the Medical College of Wisconsin between October 2012 and September 2014. Beginning in January 2014, patients began receiving 250mg of acetazolamide preoperatively; patients prior to that time did not. The visual analog scale (range 0-10) was used to assess both preoperative pain and postoperative pain. A total of 66 patients underwent laparoscopic inguinal herniorrhaphy during the study interval. Of these, 22 (33%) patients received acetazolamide preoperatively, and 44 (67%) were included as controls. Overall mean pain scores were lower in the acetazolamide group (1.9±1.45 vs 2.9±1.5, p=0.04). Specifically, patients who received acetazolamide reported lower pain scores immediately after surgery (0.6±1.2 vs 1.9±2.3, p=0.01) and on post-op day one (2.3±0.9 vs 4.0±2.1, p=0.04). Total morphine equivalents administered to manage postoperative pain were significantly less for the acetazolamide group (4.3±4.8mg) when compared to the control group (8.9±8.4mg), p=0.04. Perioperative complications did not differ between the groups (p=0.16). Acetazolamide appears to reduce pain in the immediate postoperative setting. Patients who received acetazolamide had lower pain scores postoperatively and required fewer narcotics for pain management prior to discharge.

Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients

BackgroundChronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis.Methods619 time-respiratory (minute ventilation, tidal volume and respiratory rate) and 207 time-PaCO2 observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug.ResultsThe effect of acetazolamide on minute ventilation and PaCO2 levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO2 levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily) was required to significantly increase minute ventilation (P<.001 vs pre-acetazolamide administration). Based on our model, 1000 mg per day of acetazolamide would increase minute ventilation by >0.75 L min−1 in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day.ConclusionsSimulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide.

A Case of Acute Heart Failure With Intravenous Acetazolamide Administration for Evaluation of Cerebrovascular Reactivity

A man in his seventies presented with a history of cerebral infarction with occlusion of the left middle cerebral artery, diabetes mellitus, renal dysfunction, as well as prior myocardial infarction and arteriosclerosis obliterans. About 45 min after intravenous administration of 1,000 mg of acetazolamide for acetazolamide-augmented cerebrovascular single-photon emission computed tomography, he experienced dyspnea and tightness in his chest which worsened. Hypertension, regular tachycardia, and wheezing and rales were noted. Symptoms and vital signs did not improve despite many life-saving treatments. In patients with severe coronary artery disease with low ischemic threshold, as in the present case, acetazolamide might reduce peripheral vascular resistance, increase the cardiac output ratio, increase myocardial oxygen consumption by increasing cardiac output, and induce myocardial ischemia with elevation of double product. Although the frequency of acute heart failure due to myocardial ischemia after an acetazolamide challenge may be low, its occurrence in patients with severe arteriosclerotic disease should be routinely considered. J Med Cases. 2013;4(7):495-498 doi: http://dx.doi.org/10.4021/jmc1315w

Effects of carbonic anhydrase inhibitors on pseudophakic corneal edema

Acetazolamide as inhibitor of carbonic anhydrase, in glaucoma therapy, has an effect on lowering intraocular pressure. In addition to this primary effects, we attempted to determine the effect on the cornea after phacoemulsification. In our study, we determined the effects of systemically applied dose of 500 mg of acetazolamide on the edema, thickness, and corneal morphology after phacoemulsification ,with the Anterior Segment Optical Coherence Tomography (AS OCT). The study included 53 patients who were divided into two groups. Groups were stratified by type of cataract (nuclear), age (62+/-1.5), preoperative visual acuity (5/60) Snellen table,and preoperative findings on AS-OCT. Phacoemulsification has done the same surgeon, with the same ultrasound probe length using ultrasonic force of the average value of 14 for a period of 72+/-2.5 seconds. Group of 33 patients were administered systemic acetazolamide at a dose of 250 mg per scheme 01 hours +24 hours after phacoemulsification (group I). Another group of 20 patients did not receive acetazolamide(group II). AS OCT recordings were performed before surgery, 6 hours and 24 hours after surgery. The mean value in both groups was 549+/-9 microm before surgery. Group I had average value of 648+/-6 microm after 6h, and the mean value was 612+/-4 microm after 24h. The group II,had a mean thickness of the cornea after 6 hours of 720+/-5 microm, and after 24 hours 708+/-4 microm. Morphological changes in the tomograms of the group I showed minimal creases Descemet's membrane. Postoperative visual acuity was 0,6,24h after the surgery in the I group of patients,and 0,3 in the II group. In our study the patients who administered systemic acetazolamide had significant reduction of central corneal thickness. The folds of Descemet's membrane and endothelial dysfunction in AS OCT tomograms showed less structural changes in group I. Significant better postoperative visual acuity in these patients is probably because of the smaller corneal edema after 24 h, which improves patients' comfort.

Cerebrovascular reactivity evaluated by transcranial doppler sonography in patients after aneurysmal subarachnoid haemorrhage treated with microsurgical clipping or endovascular coiling technique

<title/>Objective: To examine cerebrovascular reactivity in patients after subarachnoid haemorrhage (SAH) during long-term follow-up, using Acetazolamide test and transcranial Doppler (TCD) monitoring of blood flow velocities (BFVs), to compare of CO2 reactivity between patients after SAH treated with three different methods: surgical (clipping), endovasculary (coiling) and conservative.Methods: The study was performed in a group of 24 patients treated for SAH. Cerebrovascular reactivity (CVR) has been evaluated after intravenous administration of 1000 mg of Acetazolamide. Studied patients were divided into three groups: group I (n = 10) treated with clipping, group II (n = 8) treated with coiling and group III (n = 6) - patients with negative angiography treated conservatively.Results: Results of this study have shown that: (1) BFVs were normal in cerebral arteries and did not differ between right and left head sides, (2) CVR was normal in all studied patients, (3) method of aneurysm treatment as well as its localization had no influence on BFV and CVR, and (4) occurrence of vasospasm in early days after SAH did not result in permanent disturbances of CO2 arterial reactivity.Conclusion: BFV values in cerebral arteries were in normal range and did not differ on the left and right head sides. CVR was normal in all examinated patients. A method of the ruptured aneurysm treatment and its localization had no influence on CBFV and CRV. Vasospasm in early period after SAH did not provoke a persistent impairment of CO2 reactivity.

Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients

IntroductionAcetazolamide is commonly given to chronic obstructive pulmonary disease (COPD) patients with metabolic alkalosis. Little is known of the pharmacodynamics of acetazolamide in the critically ill. We undertook the pharmacodynamic modeling of bicarbonate response to acetazolamide in COPD patients under mechanical ventilation.MethodsThis observational, retrospective study included 68 invasively ventilated COPD patients who received one or multiple doses of 250 or 500 mg of acetazolamide during the weaning period. Among the 68 investigated patients, 207 time-serum bicarbonate observations were available for analysis. Population pharmacodynamics was modeled using a nonlinear mixedeffect model. The main covariates of interest were baseline demographic data, Simplified Acute Physiology Score II (SAPS II) at ICU admission, cause of respiratory failure, co-prescription of drugs interfering with the acid-base equilibrium, and serum concentrations of protein, creatinin, potassium and chloride. The effect of acetazolamide on serum bicarbonate levels at different doses and in different clinical conditions was subsequently simulated in silico.ResultsThe main covariates interacting with acetazolamide pharmacodynamics were SAPS II at ICU admission (P = 0.01), serum chloride (P < 0.001) and concomitant administration of corticosteroids (P = 0.02). Co-administration of furosemide significantly decreased bicarbonate elimination. Acetazolamide induced a decrease in serum bicarbonate with a dose-response relationship. The amount of acetazolamide inducing 50% of the putative maximum effect was 117 ± 21 mg. According to our model, an acetazolamide dosage > 500 mg twice daily is required to reduce serum bicarbonate concentrations > 5 mmol/L in the presence of high serum chloride levels or coadministration of systemic corticosteroids or furosemide.ConclusionsThis study identified several covariates that influenced acetazolamide pharmacodynamics and could allow a better individualization of acetazolamide dosing when treating COPD patients with metabolic alkalosis.

Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

In this study, we investigated possible separate effects of H+ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic - normoxic) ventilation over (hypoxic - normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic - normoxic) ventilation over (logPa(O2) hypoxia - logPa(O2) normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis. To determine the acute hypoxic response (AHR), we performed step decreases in end-tidal Po2 to approximately 50 Torr lasting 5 min each at three different constant end-tidal Pco2 levels. Nine subjects ingested 250 mg of acetazolamide or placebo every 8 h for 3 days in a randomized double-blind crossover design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in Pa(CO2), and a parallel leftward shift of the ventilatory CO2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arterial [H+] ([H+](a)) to higher values of [H+](a) without altering its slope, indicating that it did not affect the O2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H+ have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftward shift of the hypoxic sensitivity-[H+](a) response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated.

Renal Circulatory Effects of Acetazolamide in Patients With Essential Hypertension

Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal circulation of patients with essential hypertension. We directly infused 1000 mg of ACZ into the main renal arteries of 10 patients with essential hypertension who had undergone cardiac catheterization. We then evaluated the effects of ACZ upon heart rate, renal artery blood pressure (BP), renal artery cross-sectional area, renal Doppler blood flow velocity, renal blood flow (RBF), and renal vascular resistance (RVR). The infusion of ACZ was not associated with any significant changes in heart rate or in systolic or diastolic BP. However, the velocity-time integral was increased by 11.1% +/- 7.2%, from 17.6 +/- 1.8 to 20.0 +/- 3.7 cm (P = .009); RBF was increased by 39% +/- 21%, from 300 +/- 43 to 422 +/- 96 mL/min/m(2) (P = .002); and RVR was reduced by 38% +/- 20% from 24,351 +/- 2,291 to 17,651 +/- 2,731 dynes.sec.cm(-5) (P < .01). In contrast the cross-sectional area of the renal artery did not change. The results of the present study demonstrated that ACZ has a potent vasodilatory effect on the renal circulation of patients with essential hypertension, leading to an obvious decrease in RVR and an increase in RBF.

Intérêt de l’acétazolamide associé aux anti-inflammatoires dans le traitement de l’œdème maculaire postopératoire

To analyze the effectiveness of acetazolamide associated with topical nonsteroidal anti-inflammatory drugs (NSAIDs) and/or steroids in the treatment of postsurgical macular edema (ME). Sixteen eyes of 15 consecutive patients presenting with clinical ME 1-120 months after ophthalmologic surgery were studied retrospectively. The mean duration of ME before treatment was 5 months. All patients were treated with 250-500 mg of acetazolamide per day, associated with topical NSAIDs and/or steroids for an average of 6.9 months. The main outcome measures were the best-corrected visual acuity expressed in Log MAR, and the retinal thickness evaluated with OCT. The mean initial visual acuity was 20/100 (0.7 +/- 0.28 Log MAR), with a macular thickness of 599.67 +/-174.17 microm (average +/- standard deviation). The mean final visual acuity was 20/40 (+0.3 +/- 0.2 Log MAR) with a macular thickness of 264.69 +/- 106.59 microm. Treatment was effective in 87.5% of overall cases. The effectiveness was 100% in the subgroup treated with acetazolamide, NSAIDs, and steroids. This study suggests that medical treatment with a combination of acetazolamide, topical NSAIDs and/or steroids may be beneficial for reducing retinal thickness and improving vision in postsurgical ME.

No correlation between impairment of cerebrovascular reserve capacity and electrophysiologically assessed severity of neuropathy in noninsulin-dependent diabetes mellitus

Introduction: Microvascular abnormalities have an important role in the most frequent neurological complications of diabetes mellitus: neuropathy and cerebrovascular disorders. Severity of neuropathy as well as of cerebral microvascular damage can be quantitatively evaluated by instrumental methods like nerve conduction studies and transcranial Doppler. In the present study, we investigated whether a correlation exists between the severity of peripheral neuropathy and the impairment of cerebrovascular reserve capacity (CRC) in 20 patients with Type 2 diabetes mellitus. Methods: CRC was measured by transcranial Doppler and defined as the maximal percentage increase in blood flow velocity in the middle cerebral artery within 20 min after an intravenous dose of 1000 mg of acetazolamide. Nerve conduction studies of the median, ulnar, peroneal, and sural nerves were performed. Severity of neuropathy was scored based on conduction velocities, amplitudes, and distal latencies. Results: There was no correlation between the neuropathic score and CRC ( R=.003, P=.99). Neither CRC nor the neuropathic score correlated significantly with age, duration of diabetes, and serum values of HbA 1c, glucose, insulin, von Willebrand factor, and α 2-macroglobulin. Severity of neuropathy but not CRC correlated with microalbuminuria ( R=.47, P=.038 and R=.14, P=.54). Improper treatment reflected by HbA 1c>10% was associated with significantly more severe albuminuria, higher actual blood glucose level, higher von Willebrand factor activity, and marginally higher neuropathic score (21 vs. 13, P=.096), but was not associated with CRC (44% vs. 42%, P=.81). When duration of diabetes was dichotomized to 15 years and less or over 15 years, CRC was significantly smaller (35% vs. 50%, P=.036) and neuropathy was more severe in the subgroup with longer diabetes duration (19 vs. 11.5 points, P=.07). Conclusions: Although both CRC and peripheral nerve function are affected more severely in patients with long-lasting Type 2 diabetes mellitus, damage in the cerebrovascular system and in the long peripheral nerves occur independently. As in diabetes mellitus pathological changes in autonomic and large peripheral nerves develop simultaneously, decreased CRC in diabetic patients might be predominantly due to structural changes of resistance arteries or to metabolic than to neurogenic factors.

Impairment of cerebrovascular reactivity to acetazolamide in patients with normal pressure hydrocephalus.

Cerebrovascular reactivity (CVR) to acetazolamide was investigated in 41 patients with normal pressure hydrocephalus (NPH). The aetiology was subarachnoid haemorrhage in 20 patients, trauma in nine, brain tumour in three and idiopathic in nine. Mean cerebral blood flow (CBF) of the whole brain was measured by performing first-pass radionuclide angiography using 99Tcm-hexamethylpropylene++ amine oxime. Cerebrovascular reactivity was measured as the percentage change from the baseline mean CBF value after the administration of 500 mg of acetazolamide. Cerebrovascular reactivity was significantly (P < 0.001) reduced in patients with the complete triad of NPH (1.4 +/- 3.1%), regardless of the aetiology, compared with normal controls (14.7 +/- 3.3%). Patients with the incomplete triad also showed significantly (P < 0.05) reduced CVR (9.6 +/- 5.4%). Patients with the complete triad had significantly (P < 0.001) lower CVR than those with the incomplete triad. Post-operative CVR in both groups (20 patients with the complete triad and 9 patients with the incomplete triad) increased significantly, from 1.5 +/- 3.5% to 10.0 +/- 5.5% (P < 0.001) and from 8.7 +/- 4.9% to 14.9 +/- 5.4% (P < 0.05), respectively. Cerebrovascular reactivity is impaired in patients with NPH regardless of the aetiology and improves after shunting.

Response of cerebral blood flow and cerebrovascular reactivity to acetazolamide in patients with dementia and idiopathic normal-pressure hydrocephalus

The responses of cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to administration of acetazolamide were investigated in 16 patients with dementia and ventriculomegaly to clarify the cerebral hemodynamics in patients with idiopathic normal-pressure hydrocephalus (NPH). The mean CBF velocity in the whole brain was measured by the Patlak plot method by using technetium-99m hexamethylpropyleneamine oxime single-photon emission computerized tomography. The CVR values were obtained from the response to administration of 500 mg of acetazolamide and calculated as the percentage of change from the baseline mean CBF value. The mean CBF value was significantly reduced (p &lt; 0.01) in six patients with (35.2 ± 5 ml/100 g/minute) and 10 patients without (33.5 ± 2.8 ml/100 g/minute) NPH compared with the age-matched normal controls (40.8 ± 3.2 ml/100 g/minute), showing no significant difference. The CVR was significantly impaired in patients with NPH (0.8 ± 1.7%; p &lt; 0.001), whereas in patients without NPH preserved CVR (11.3 ± 3%) was demonstrated compared with the normal controls (14.7 ± 1.1%). In patients with NPH a significantly lower CVR (p &lt; 0.001) was shown than in those without NPH. The CVR significantly increased (p &lt; 0.001) after placement of a shunt in patients with NPH. Reductions in both CBF and CVR may be diagnostic indicators of NPH in patients with dementia in whom ventriculomegaly is present. In patients with dementia and idiopathic NPH both reduced CBF and extremely impaired CVR are shown. The results of the present study suggest that ischemia due to the process of NPH is responsible for the reduction of CBF and manifestation of symptoms in patients with idiopathic NPH.

The Effects of Acetazolamide on Arterial Pressure Variability During REM Sleep in the Rat

Sone, M., H. Sei, Y. Morita, T. Ogura and S. Sone.The effects of acetazolamide on arterial pressure variability during REM sleep in the rat.PHYSIOL BEHAV 63(2) 213–218, 1998.—During rapid eye movement (REM) sleep, the arterial pressure (AP) undergoes large fluctuations in the rat, cat, and other mammals, including humans, and it has been suggested that this effect originates in the forebrain. In addition, acetazolamide (ACTZ), a carbonic anhydrase inhibitor, is known to be effective in the treatment of central sleep apnea or epilepsy. The aim of the present study was to analyze the effects of ACTZ on EEG theta rhythm and AP variability during REM sleep in rats. Treatment consisted of intraperitoneal injection of 5 mg of ACTZ in 0.5 mL of saline (n = 6) or 0.5 mL of vehicle alone (n = 6). We then recorded and analyzed the mean AP (MAP) variations during different sleep phases, using a telemetric system. Our results show: 1) Significant decreases in the coefficient of variation of MAP, in the very-low frequency (0.025 - 0.225 Hz) component of the power spectral density of the AP and in theta frequency in the electroencephalogram, were seen in the ACTZ-treated group during REM sleep compared with controls, whereas no significant difference was found between the two groups in non-REM sleep. There was no significant difference in sleep duration, average MAP, and heart rate between the groups. Our data suggest that ACTZ may act as a stabilizing factor preventing AP fluctuations during REM sleep.