Effects of two carbonic anhydrase inhibitors on exercise performance in acute hypoxia.

IF 3.3 3区 医学 Q1 PHYSIOLOGY
Journal of applied physiology Pub Date : 2024-12-01 Epub Date: 2024-10-31 DOI:10.1152/japplphysiol.00589.2024
Jou-Chung Chang, Benjamin P Thompson, Connor J Doherty, Leah M Mann, Antonia N Berdeklis, Glen E Foster, A Russell Tupling, Erik R Swenson, Paolo B Dominelli
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引用次数: 0

Abstract

Acute mountain sickness (AMS) occurs due to rapid altitude ascents and/or insufficient acclimatization. Acetazolamide (AZ) is commonly prescribed for AMS prophylaxis but inhibits exercise performance. Methazolamide (MZ), an analogous drug, has similar prophylactic benefits but does not impair isolated muscle mass exercise performance in normoxia. We sought to compare whole body exercise performance in acute hypoxia (fraction of inspired oxygen, [Formula: see text] = 0.15) between AZ, MZ, and placebo (PLA). Fifteen healthy participants completed five testing visits: day 1 for maximal exercise test, day 2 for familiarization, and days 3-5 were the experimental visits. Each experimental visit involved a 5-km hypoxic cycling time trial (TT) performed after a 2-day dosing protocol of either AZ (250 mg three times a day), MZ (100 mg twice a day), or PLA (three times a day); the order was randomized and double-blinded. Before exercise, capillary blood samples were taken, and maximal voluntary contractions of quadriceps were performed. AZ and MZ resulted in a partially compensated metabolic acidosis at rest compared with PLA [capillary hydrogen ions (H+) 47 ± 3, 43 ± 2, and 39 ± 2 nmol for AZ, MZ, and PLA respectively, P < 0.01]. Time to complete 5 km with PLA (562 ± 32 s, P < 0.01) was significantly faster than AZ and MZ (577 ± 38 vs. 581 ± 37 s, respectively), with no differences between AZ and MZ (P = 0.96). There were no differences in average ventilation (124 ± 27, 127 ± 24, 127 ± 19 L/min) and oxyhemoglobin saturation (87 ± 2, 88 ± 2, 88 ± 3%) between AZ, MZ, and PLA, respectively (P > 0.05). Overall, both AZ and MZ impair whole body exercise performance in acute normobaric hypoxia.NEW & NOTEWORTHY Administration of acetazolamide (AZ) and methazolamide (MZ) both resulted in a significantly slower 5-km time trial in acute normobaric hypoxia compared with a placebo. Both drugs lead to a partially compensated metabolic acidosis, but ventilation and oxyhemoglobin saturation were not different across the conditions. Overall, acetazolamide and methazolamide both impaired whole body exercise performance in acute normobaric hypoxia but potentially have different mechanisms of action.

两种碳酸酐酶抑制剂对急性缺氧状态下运动表现的影响
急性高山反应是由于快速上升海拔和/或适应不足造成的。乙酰唑胺(AZ)是预防高山反应的常用药物,但会抑制运动表现。甲氮唑胺(MZ)是一种类似的药物,具有类似的预防作用,但在常氧状态下不会影响孤立肌肉群的运动表现。我们试图比较 AZ、MZ 和安慰剂(PLA)在急性缺氧(FIO2 = 0.15)情况下的全身运动表现。15 名健康参与者完成了 5 次测试:第 1 天为最大运动量测试,第 2 天为熟悉测试,第 3-5 天为实验测试。每个实验访问都包括 5 公里缺氧自行车计时测试,测试前两天分别服用 AZ(250 毫克,一天一次)、MZ(100 毫克,一天两次)或 PLA(一天一次);测试顺序随机且双盲。运动前采集毛细血管血样,并进行股四头肌的最大自主收缩。与 PLA 相比,AZ 和 MZ 在静息时会导致部分代偿性代谢性酸中毒(AZ、MZ 和 PLA 的毛细血管 H+ 分别为 47±3、43±2、39±2 nmol,P0.05)。总之,AZ 和 MZ 都会损害急性常压缺氧下的全身运动能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.00
自引率
9.10%
发文量
296
审稿时长
2-4 weeks
期刊介绍: The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.
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