Reduction of carbonic anhydrase activity is associated with amelioration of obstructive sleep apnea.

IF 2
Ali M Komai, Saliha Musovic, Kaj Stenlöf, Ludger Grote, Ding Zou, Jan Hedner
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Abstract

Background: The carbonic anhydrase (CA) enzyme plays an important role in the equilibration of carbon dioxide and bicarbonate (HCO3) under the production of H+ ions. Emerging evidence suggest that CA activity may play a fundamental regulatory role on respiratory control mechanisms in obstructive sleep apnea (OSA). Clinical trials suggest that CA inhibitors significantly reduce OSA.

Methods: Data from three separate cohorts of healthy volunteers and patients with OSA were used to quantify CA activity in whole blood and cerebrospinal fluid (CSF). The influence of the CA inhibitory drugs acetazolamide and sulthiame, on CA activity in-vitro/in-vivo, was assessed. The association between CA-inhibitor plasma concentration and HCO3, as well as the influence of HCO3 on the apnea-hypopnea severity was determined.

Results: Stability of CA activity in stored blood was high. CA activity in whole blood contained five times higher activity compared with CSF. The CA-inhibitory drugs dose-dependently reduced CA activity in-vitro/in-vivo. The CA inhibitor sulthiame reduced venous HCO3 concentration (P = 0.022). The reduction of HCO3 was linked to improvement of OSA (P = 0.040).

Conclusions: CA-inhibitory drugs reduced CA activity in whole blood suggesting a therapeutic role of CA inhibition in OSA. The findings also suggest that an activated CA system may constitute a pathophysiological mechanism in some forms of OSA.

Clinical trial registration: N/A.

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碳酸酐酶活性的降低与阻塞性睡眠呼吸暂停的改善有关。
背景:碳酸酐酶(CA)在氢离子生成过程中对二氧化碳和碳酸氢盐(HCO3)的平衡起着重要作用。新出现的证据表明,CA活性可能在阻塞性睡眠呼吸暂停(OSA)的呼吸控制机制中发挥基础性调节作用。临床试验表明,CA抑制剂可显著降低OSA。方法:使用来自健康志愿者和OSA患者的三个独立队列的数据来量化全血和脑脊液(CSF)中的CA活性。评估了CA抑制药物乙酰唑胺和磺胺对CA体外/体内活性的影响。确定ca抑制剂血浆浓度与HCO3的关系,以及HCO3对呼吸暂停-低通气严重程度的影响。结果:贮藏血CA活性稳定性高。全血CA活性比CSF高5倍。CA抑制药物剂量依赖性地降低体内/体外CA活性。CA抑制剂磺胺可降低静脉HCO3浓度(P = 0.022)。HCO3的降低与OSA的改善相关(P = 0.040)。结论:CA抑制药物降低了全血CA活性,提示CA抑制在OSA中的治疗作用。研究结果还表明,激活的CA系统可能在某些形式的OSA中构成病理生理机制。临床试验注册:无。
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