Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, BC, Canada.
Exp Physiol. 2020 Feb;105(2):293-301. doi: 10.1113/EP088058. Epub 2019 Oct 26.
What is the central question of this study? Acetazolamide and methazolamide both reduce hypoxic pulmonary vasoconstriction equally, but methazolamide does not impair skeletal muscle function. The effect of methazolamide on respiratory control in humans is not yet known. What is the main finding and its importance? Similar to acetazolamide after chronic oral administration, methazolamide causes a metabolic acidosis and shifts the ventilatory CO response curve leftwards without reducing O sensitivity. The change in ventilation over the change in log provides a more accurate measure of hypoxic sensitivity than the change in ventilation over the change in arterial oxyhaemoglobin saturation.
Acetazolamide is used to prevent/treat acute mountain sickness and both central and obstructive sleep apnoea. Methazolamide, like acetazolamide, reduces hypoxic pulmonary vasoconstriction, but has fewer side-effects, including less impairment of skeletal muscle function. Given that the effects of methazolamide on respiratory control in humans are unknown, we compared the effects of oral methazolamide and acetazolamide on ventilatory control and determined the ventilation-log relationship in humans. In a double-blind, placebo-controlled, randomized cross-over design, we studied the effects of acetazolamide (250 mg three times daily), methazolamide (100 mg twice daily) and placebo in 14 young male subjects who were exposed to 7 min of normoxic hypercapnia and to three levels of eucapnia and hypercapnic hypoxia. With placebo, methazolamide and acetazolamide, the CO sensitivities were 2.39 ± 1.29, 3.27 ± 1.82 and 2.62 ± 1.79 l min mmHg (n.s.) and estimated apnoeic thresholds 32 ± 3, 28 ± 3 and 26 ± 3 mmHg, respectively (P < 0.001, placebo versus methazolamide and acetazolamide). The relationship between ventilation ( ) and log (using arterialized venous in hypoxia) was linear, and neither agent influenced the relationship between hypoxic sensitivity ( ) and arterial [H ]. Using rather than Δ /Δ arterial oxyhaemoglobin saturation enables a more accurate estimation of oxygenation and ventilatory control in metabolic acidosis/alkalosis when right- or leftward shifts of the oxyhaemoglobin saturation curve occur. Given that acetazolamide and methazolamide have similar effects on ventilatory control, methazolamide might be preferred for indications requiring the use of a carbonic anhydrase inhibitor, avoiding some of the negative side-effects of acetazolamide.
这项研究的核心问题是什么？乙酰唑胺和甲唑胺均可同等程度地降低低氧性肺血管收缩，但甲唑胺不会损害骨骼肌功能。甲唑胺对人类呼吸控制的影响尚不清楚。主要发现及其重要性是什么？与慢性口服乙酰唑胺相似，甲唑胺引起代谢性酸中毒，并使通气 CO 反应曲线向左移位，而不降低 O 敏感性。通气变化与对数的变化提供了一种比通气变化与动脉血氧饱和度变化更准确的低氧敏感性测量方法。
乙酰唑胺用于预防/治疗急性高山病和中枢性及阻塞性睡眠呼吸暂停。甲唑胺与乙酰唑胺一样，可降低低氧性肺血管收缩，但副作用较少，包括骨骼肌功能损害较少。鉴于甲唑胺对人类呼吸控制的影响尚不清楚，我们比较了口服甲唑胺和乙酰唑胺对通气控制的影响，并确定了人类的通气-对数关系。在一项双盲、安慰剂对照、随机交叉设计中，我们研究了 14 名年轻男性受试者在暴露于 7 分钟的正常高碳酸血症和三个水平的低碳酸血症和高碳酸血症缺氧时，服用乙酰唑胺（250mg，每日 3 次）、甲唑胺（100mg，每日 2 次）和安慰剂的效果。服用安慰剂、甲唑胺和乙酰唑胺时，CO 敏感性分别为 2.39±1.29、3.27±1.82 和 2.62±1.79 l/min/mmHg（无统计学意义），估计的呼吸暂停阈值分别为 32±3、28±3 和 26±3mmHg（P<0.001，安慰剂与甲唑胺和乙酰唑胺相比）。通气（ ）与对数（在缺氧时使用动脉化静脉）的关系是线性的，两种药物均不影响低氧敏感性（ ）与动脉[H]之间的关系。使用 而不是 Δ /Δ 动脉血氧饱和度，当血氧饱和度曲线发生右移或左移时，可更准确地估计代谢性酸中毒/碱中毒时的氧合和通气控制。由于乙酰唑胺和甲唑胺对通气控制的影响相似，因此在需要使用碳酸酐酶抑制剂的情况下，甲唑胺可能更受青睐，可以避免乙酰唑胺的一些负面副作用。
