Teppema Luc J, Balanos George M, Steinback Craig D, Brown Allison D, Foster Glen E, Duff Henry J, Leigh Richard, Poulin Marc J
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Am J Respir Crit Care Med. 2007 Feb 1;175(3):277-81. doi: 10.1164/rccm.200608-1199OC. Epub 2006 Nov 9.
Acute mountain sickness (AMS) may affect individuals who (rapidly) ascend to altitudes higher than 2,000-3,000 m. A more serious consequence of rapid ascent may be high-altitude pulmonary edema, a hydrostatic edema associated with increased pulmonary capillary pressures. Acetazolamide is effective against AMS, possibly by increasing ventilation and cerebral blood flow (CBF). In animals, it inhibits hypoxic pulmonary vasoconstriction.
We examined the influence of acetazolamide on the response to hypoxia of ventilation, CBF, and pulmonary vascular resistance (PVR).
In this double-blind, placebo-controlled, randomized study, nine subjects ingested 250 mg acetazolamide every 8 h for 3 d. On the fourth test day, we measured the responses of ventilation, PVR, and CBF to acute isocapnic hypoxia (20 min) and sustained poikilocapnic hypoxia (4 h). Ventilation was measured with pneumotachography. Hypoxia was achieved with dynamic end-tidal forcing. The maximum pressure difference across the tricuspid valve (DeltaPmax, a good index of PVR) was measured with Doppler echocardiography. CBF was measured by transcranial Doppler ultrasound.
In normoxia, acetazolamide increased ventilation and reduced DeltaPmax, but did not influence CBF. The ventilatory and CBF responses to acute isocapnic hypoxia were unaltered, but the rise in DeltaPmax was reduced by 57%. The increase in DeltaPmax by sustained poikilocapnic hypoxia observed after placebo was reduced by 34% after acetazolamide, the ventilatory response was increased, but the CBF response remained unaltered.
Acetazolamide has complex effects on ventilation, PVR, and CBF that converge to optimize brain oxygenation and may be a valuable means to prevent/treat high-altitude pulmonary edema.
急性高原病（AMS）可能影响（迅速）攀升至海拔高于2000 - 3000米的个体。快速上升的一个更严重后果可能是高原肺水肿，这是一种与肺毛细血管压力增加相关的静水压性水肿。乙酰唑胺对AMS有效，可能是通过增加通气和脑血流量（CBF）。在动物中，它可抑制缺氧性肺血管收缩。
我们研究了乙酰唑胺对通气、CBF和肺血管阻力（PVR）对缺氧反应的影响。
在这项双盲、安慰剂对照、随机研究中，9名受试者每8小时服用250毫克乙酰唑胺，共3天。在第四个测试日，我们测量了通气、PVR和CBF对急性等碳酸血症性缺氧（20分钟）和持续性异碳酸血症性缺氧（4小时）的反应。通气通过呼吸流速描记法测量。通过动态呼气末强制实现缺氧。用多普勒超声心动图测量三尖瓣跨瓣最大压差（DeltaPmax，PVR的良好指标）。通过经颅多普勒超声测量CBF。
在常氧状态下，乙酰唑胺增加通气并降低DeltaPmax，但不影响CBF。对急性等碳酸血症性缺氧的通气和CBF反应未改变，但DeltaPmax的升高降低了57%。安慰剂后观察到的持续性异碳酸血症性缺氧引起的DeltaPmax增加在乙酰唑胺后降低了34%，通气反应增加，但CBF反应未改变。
乙酰唑胺对通气、PVR和CBF有复杂影响，这些影响共同作用以优化脑氧合，可能是预防/治疗高原肺水肿的一种有价值手段。
