Birk Steffen, Kruuse Christina, Petersen Kenneth A, Jonassen Olga, Tfelt-Hansen Peer, Olesen Jes
Danish Headache Center and Department of Neurology, University of Copenhagen, Glostrup University Hospital, Glostrup, Copenhagen, Denmark.
J Cereb Blood Flow Metab. 2004 Dec;24(12):1352-8. doi: 10.1097/01.WCB.0000143536.22131.D7.
Cilostazol, an inhibitor of phosphodiesterase (PDE) type 3, is used clinically in peripheral artery disease. PDE3 inhibitors may be clinically useful in the treatment of delayed cerebral vasospasm after subarachnoid hemorrhage. The authors present the first results on the effect of cilostazol on cerebral hemodynamics in normal participants. In this double-blind, randomized, crossover study, 200 mg cilostazol or placebo was administered orally to 12 healthy participants. Cerebral blood flow was measured using 133Xe inhalation and single photon emission computerized tomography. Mean flow velocity in the middle cerebral arteries (VMCA) was measured with transcranial Doppler, and the superficial temporal and radial arteries diameters were measured with ultrasonography. During the 4-hour observation period, there was no effect on systolic blood pressure (P = 0.28), but diastolic blood pressure decreased slightly compared with placebo (P = 0.04). VMCA decreased 21.5 +/- 5.7% after cilostazol and 5.5 +/- 12.2% after placebo (P = 0.02, vs. placebo), without any change in global or regional cerebral blood flow. The superficial temporal artery diameter increased 17.6 +/- 12.3% (P < 0.001 vs. baseline) and radial artery diameter increased 12.6 +/- 8.6% (P < 0.001 vs. baseline). Adverse events, especially headache, were common. The findings suggest that cilostazol is an interesting candidate for future clinical trials of delayed cerebral vasospasm.
西洛他唑是一种磷酸二酯酶3（PDE）抑制剂，临床上用于治疗外周动脉疾病。PDE3抑制剂在治疗蛛网膜下腔出血后的迟发性脑血管痉挛方面可能具有临床应用价值。作者首次展示了西洛他唑对正常受试者脑血流动力学影响的研究结果。在这项双盲、随机、交叉研究中，12名健康受试者口服200毫克西洛他唑或安慰剂。使用吸入133Xe和单光子发射计算机断层扫描测量脑血流量。用经颅多普勒测量大脑中动脉的平均血流速度（VMCA），用超声测量颞浅动脉和桡动脉直径。在4小时的观察期内，对收缩压没有影响（P = 0.28），但与安慰剂相比，舒张压略有下降（P = 0.04）。服用西洛他唑后VMCA下降21.5 +/- 5.7%，服用安慰剂后下降5.5 +/- 12.2%（P = 0.02，与安慰剂相比），全脑或局部脑血流量无任何变化。颞浅动脉直径增加17.6 +/- 12.3%（与基线相比P < 0.001），桡动脉直径增加12.6 +/- 8.6%（与基线相比P < 0.001）。不良事件很常见，尤其是头痛。这些发现表明，西洛他唑是未来迟发性脑血管痉挛临床试验的一个有吸引力的候选药物。
