Abstract：
BACKGROUND: Acetazolamide (AZA) improves nocturnal and daytime blood oxygenation in patients with pulmonary vascular disease (PVD), defined as pulmonary arterial and distal chronic thromboembolic pulmonary hypertension (CTEPH), and may improve exercise performance.
METHODS: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout.
RESULTS: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol. Maximum load was similar after 5 weeks of AZA versus placebo (113 ± 9 vs. 117 ± 9 watts [W]), mean difference -4 W (95% CI: -9 to 1, p = 0.138). With AZA, maximum (max)-exercise partial pressure of O2 (PaO2) was significantly higher by 1.1 kPa (95% CI: 0.5-1.8, p = 0.003), while arterial pH and partial pressure of CO2 were significantly lower. Gas exchange threshold was reached at a higher load with AZA (108 ± 8 W vs. 97 ± 8 W) and was therefore delayed by 11 W (95% CI: 3-19, p = 0.013), while the ventilatory equivalent for O2 and CO2 were significantly higher at both the max-exercise and gas exchange threshold with AZA versus placebo.
CONCLUSIONS: AZA for 5 weeks did not significantly change maximum exercise capacity in patients with PVD despite a significant increase in PaO2. The beneficial effects of increased blood oxygenation may have been diminished by increased ventilation due to AZA-induced metabolic acidosis and increased dyspnea.
METHODS: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout.
RESULTS: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol. Maximum load was similar after 5 weeks of AZA versus placebo (113 ± 9 vs. 117 ± 9 watts [W]), mean difference -4 W (95% CI: -9 to 1, p = 0.138). With AZA, maximum (max)-exercise partial pressure of O2 (PaO2) was significantly higher by 1.1 kPa (95% CI: 0.5-1.8, p = 0.003), while arterial pH and partial pressure of CO2 were significantly lower. Gas exchange threshold was reached at a higher load with AZA (108 ± 8 W vs. 97 ± 8 W) and was therefore delayed by 11 W (95% CI: 3-19, p = 0.013), while the ventilatory equivalent for O2 and CO2 were significantly higher at both the max-exercise and gas exchange threshold with AZA versus placebo.
CONCLUSIONS: AZA for 5 weeks did not significantly change maximum exercise capacity in patients with PVD despite a significant increase in PaO2. The beneficial effects of increased blood oxygenation may have been diminished by increased ventilation due to AZA-induced metabolic acidosis and increased dyspnea.
摘要：
背景：乙酰唑胺（AZA）可改善肺血管疾病（PVD）患者的夜间和白天血氧，定义为肺动脉和远端慢性血栓栓塞性肺动脉高压（CTEPH），并可能提高运动表现。
方法：我们研究了在随机对照研究中，在PVD患者中，在递增循环斜坡运动期间，AZA（250mgbid）与安慰剂对最大负荷的影响，双盲,交叉设计，分开2周的冲洗。
结果：25例患者（12例肺动脉高压，13CTEPH,40%的女性,年龄62±15岁）根据方案完成试验。AZA与安慰剂治疗5周后的最大负荷相似（113±9vs.117±9瓦[W]),平均差-4W（95%CI：-9至1，p=0.138）。有了AZA,最大（max）-运动氧分压（PaO2）显着升高1.1kPa（95％CI：0.5-1.8，p=0.003），而动脉pH值和CO2分压显著降低。AZA在较高的负载下达到了气体交换阈值（108±8W与97±8W），因此延迟了11W（95％CI：3-19，p=0.013），而与安慰剂相比，AZA在最大运动阈值和气体交换阈值下的O2和CO2通气当量均显着较高。
结论：AZA治疗5周并未显著改变PVD患者的最大运动能力，尽管PaO2显著升高。由于AZA诱导的代谢性酸中毒和增加的呼吸困难，增加的通气可能会减少血液氧合增加的有益作用。
方法：我们研究了在随机对照研究中，在PVD患者中，在递增循环斜坡运动期间，AZA（250mgbid）与安慰剂对最大负荷的影响，双盲,交叉设计，分开2周的冲洗。
结果：25例患者（12例肺动脉高压，13CTEPH,40%的女性,年龄62±15岁）根据方案完成试验。AZA与安慰剂治疗5周后的最大负荷相似（113±9vs.117±9瓦[W]),平均差-4W（95%CI：-9至1，p=0.138）。有了AZA,最大（max）-运动氧分压（PaO2）显着升高1.1kPa（95％CI：0.5-1.8，p=0.003），而动脉pH值和CO2分压显著降低。AZA在较高的负载下达到了气体交换阈值（108±8W与97±8W），因此延迟了11W（95％CI：3-19，p=0.013），而与安慰剂相比，AZA在最大运动阈值和气体交换阈值下的O2和CO2通气当量均显着较高。
结论：AZA治疗5周并未显著改变PVD患者的最大运动能力，尽管PaO2显著升高。由于AZA诱导的代谢性酸中毒和增加的呼吸困难，增加的通气可能会减少血液氧合增加的有益作用。
