Huang S Y, McCullough R E, McCullough R G, Micco A J, Manco-Johnson M, Weil J V, Reeves J T
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Respir Physiol. 1988 Jun;72(3):315-26. doi: 10.1016/0034-5687(88)90090-4.
Prior reports indicate that acetazolamide, an inhibitor of carbonic anhydrase, in moderate doses reduces symptoms of acute mountain sickness, and in large doses increases cerebral blood flow. The effect on flow is not known for a moderate dose, but were flow to increase, then increased cerebral oxygen delivery would be one mechanism of benefit from acetazolamide at high altitude. We utilized Doppler ultrasound in 8 volunteers to determine whether a usual acetazolamide dose (250 mg three times daily) would increase flow velocities in internal carotid and vertebral arteries. Acetazolamide during normoxia decreased pHa, PaCO2, and PETCO2, but baseline flow velocity remained unchanged. In 2 subjects without acetazolamide, voluntary hyperventilation decreased both PETCO2 and flow velocity. Both hypoxia and hypercapnia caused increases in arterial velocities. The increases were not altered by acetazolamide administration. In one subject, 1 g acetazolamide by acute i.v. injection induced an increase in flow velocity (40%) concomitant with a 5 mm Hg decrease in PETCO2, confirming prior reports using similar intravenous dose. In doses employed for prevention of acute mountain sickness, acetazolamide induced metabolic acidosis and may have prevented the fall in velocity usually associated with hypocapnia, but it neither increased baseline cerebral blood flow velocity nor velocity responses to hypoxia and hypercapnia. Benefit of acetazolamide at high altitude may relate to mechanisms other than increased cerebral blood flow.
先前的报告表明，碳酸酐酶抑制剂乙酰唑胺，中等剂量可减轻急性高原病症状，大剂量可增加脑血流量。中等剂量对血流量的影响尚不清楚，但如果血流量增加，那么增加的脑氧输送将是乙酰唑胺在高海拔地区发挥益处的一种机制。我们对8名志愿者使用多普勒超声来确定常规剂量的乙酰唑胺（每日三次，每次250毫克）是否会增加颈内动脉和椎动脉的血流速度。常氧状态下，乙酰唑胺降低了动脉血pH值、动脉血二氧化碳分压和呼气末二氧化碳分压，但基线血流速度保持不变。在2名未服用乙酰唑胺的受试者中，自主过度通气降低了呼气末二氧化碳分压和血流速度。低氧和高碳酸血症均导致动脉血流速度增加。这些增加不受乙酰唑胺给药的影响。在一名受试者中，静脉注射1克乙酰唑胺可使血流速度增加（40%），同时呼气末二氧化碳分压降低5毫米汞柱，证实了先前使用类似静脉剂量的报告。在用于预防急性高原病的剂量下，乙酰唑胺可诱发代谢性酸中毒，可能阻止了通常与低碳酸血症相关的血流速度下降，但它既未增加基线脑血流速度，也未增加对低氧和高碳酸血症的血流速度反应。乙酰唑胺在高海拔地区的益处可能与增加脑血流量以外的机制有关。
