BACKGROUND & AIMS:
:Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In animals, methazolamide, a methylated analog of acetazolamide and an equally potent CA inhibitor, reportedly exacerbates fatigue less than acetazolamide. Accordingly, we sought to determine, in humans, if methazolamide would attenuate diaphragm and dorsiflexor fatigue compared with acetazolamide. Healthy men (dorsiflexor: n = 12; diaphragm: n = 7) performed fatiguing exercise on three occasions, after ingesting acetazolamide (250 mg three times a day) and then in random order, methazolamide (100 mg twice a day) or placebo for 48 h. For both muscles, subjects exercised at a fixed intensity until exhaustion on acetazolamide, with subsequent iso-time and -workload trials. Diaphragm exercise was performed using a threshold-loading device, while dorsiflexor exercise was isometric. Neuromuscular function was determined pre- and postexercise by potentiated transdiaphragmatic twitch pressure and dorsiflexor torque in response to stimulation of the phrenic and fibular nerve, respectively. Diaphragm contractility 3-10 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82 ± 10, 87 ± 9, and 91 ± 8% of pre-exercise value; P < 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61 ± 11 vs. 57 ± 13% of baseline, P < 0.05). In normoxia, methazolamide leads to less neuromuscular fatigue than acetazolamide, indicating a possible benefit for clinical use or in the prophylaxis of acute mountain sickness. NEW & NOTEWORTHY Acetazolamide, a carbonic anhydrase inhibitor, may worsen diaphragm and locomotor muscle fatigue after exercise; whereas, in animals, methazolamide does not impair diaphragm function. Compared with both methazolamide and the placebo, acetazolamide significantly compromised dorsiflexor function at rest and after exhaustive exercise. Similarly, diaphragm function was most compromised on acetazolamide followed by methazolamide and placebo. Methazolamide may be preferable over acetazolamide for clinical use and altitude illness prophylaxis to avoid skeletal muscle dysfunction.
背景与目标:
: 乙酰唑胺,一种碳酸酐酶 (CA) 抑制剂,用于临床和预防急性高山病,恶化动物和人类的骨骼肌乏力。在动物中,据报道,甲唑胺 (乙酰唑胺的甲基化类似物和同样有效的CA抑制剂) 比乙酰唑胺减轻乏力。因此,我们试图确定与乙酰唑胺相比,在人类中,甲唑胺是否会减轻隔膜和背屈肌乏力。健康男性 (背屈肌: n = 12; 膈肌: n = 7) 在摄入乙酰唑胺 (250毫克,每天三次) 后,进行三次疲劳运动,然后随机顺序,甲唑胺 (100毫克,每天两次) 或安慰剂48小时。对于两种肌肉,受试者都以固定的强度运动,直到使用乙酰唑胺耗尽为止,并进行后续的等时间和工作量试验。隔膜运动是使用阈值加载装置进行的,而背屈肌运动是等距的。运动前和运动后,分别通过增强膈肌和腓骨神经的刺激来确定神经肌肉功能。与甲唑胺或安慰剂相比,乙酰唑胺运动后3-10分钟的膈肌收缩力受损更多 (82 ± 10、87 ± 9和91 ± 8% 的运动前值; P <0.05)。同样,乙酰唑胺的背屈肌乏力大于甲唑胺 (平均抽搐扭矩为61 ± 11,而基线的13% 为57 ± ,P <0.05)。在常氧状态下,甲唑胺比乙酰唑胺引起的神经肌肉乏力更少,表明可能对临床使用或预防急性高山病有益。新的和值得注意的乙酰唑胺,一种碳酸酐酶抑制剂,可能会加剧运动后的diaphragm肌和运动肌肉乏力; 而在动物中,甲唑胺不会损害diaphragm肌功能。与methazolamide和安慰剂相比,乙酰唑胺在休息和力竭运动后显着降低了背屈功能。同样,对乙酰唑胺,其次是甲唑酰胺和安慰剂,隔膜功能受损最大。在临床使用和预防高原疾病以避免骨骼肌功能障碍方面,甲唑胺比乙酰唑胺更可取。