乙酰唑胺,一种临床使用的碳酸酐酶(CA)抑制剂,用于预防急性高山病,加重骨骼肌疲劳在动物和人类。在动物中,醋甲唑胺,乙酰唑胺的甲基化类似物和同样有效的CA抑制剂,据报道,比乙酰唑胺更容易加剧疲劳。因此,我们试图确定,在人类中,与乙酰唑胺相比,喹唑胺是否会减弱隔膜和背屈肌疲劳。健康男性(背屈:n=12;隔膜:n=7)进行了三次疲劳运动,摄入乙酰唑胺(每天三次250毫克)后,然后按随机顺序,醋甲唑胺(每天两次100毫克)或安慰剂48小时。对于两个肌肉,受试者以固定的强度进行锻炼,直到对乙酰唑胺耗尽,随后的等时和工作量试验。使用阈值加载装置进行隔膜锻炼,而背屈肌运动是等距的。运动前和运动后,通过增强的跨the肌抽搐压力和背屈肌扭矩来确定神经肌肉功能,以响应the神经和腓骨神经的刺激,分别。运动后3-10分钟,乙酰唑胺的膈肌收缩力受损程度高于喹唑胺或安慰剂(运动前值的82±10、87±9和91±8%;P<0.05)。同样,乙酰唑胺的背屈肌疲劳大于醋甲唑胺(平均抽搐扭矩为61±11与基线的57±13%,P<0.05)。在常氧症中,与乙酰唑胺相比,喹唑胺导致更少的神经肌肉疲劳,表明临床使用或预防急性高山病的可能益处。NEW&NOTEWorthy乙酰唑胺,碳酸酐酶抑制剂,运动后可能会加剧隔膜和运动肌肉疲劳;然而,在动物中,醋甲唑胺不会损害隔膜功能。与醋甲唑胺和安慰剂相比,乙酰唑胺在休息和力竭运动后显着损害背屈功能。同样,对乙酰唑胺的膈肌功能损害最严重,其次是醋甲唑胺和安慰剂.在临床使用和预防高原疾病方面,甲唑胺可能比乙酰唑胺更可取,以避免骨骼肌功能障碍。
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.