A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke
A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke
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DOI：
10.1161/strokeaha.106.480699
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发表时间：
2007-07-01
期刊：
影响因子：
8.3
通讯作者：
Chamorro, Angel
中科院分区：
文献类型：
--
作者：
Amaro, Sergio;Soy, Dolors;Chamorro, Angel
背景和目的 - 尿酸 (UA) 增加重组组织纤溶酶原激活剂 (rt-PA) 在实验性缺血中的神经保护作用。在中风患者中，UA水平升高与更好的中风恢复有关，但UA和rt-PA双重给药的临床安全性尚不清楚。 方法 - 采用双盲设计，我们评估了接受rt-PA治疗的急性中风患者中外源性UA的安全性。患者被随机分配接受 500 mL 5% 甘露醇/0.1% 碳酸锂静脉注射溶液（载体组，n = 8）或 500 或 1000 mg UA（n = 16）。确定了第 90 天的安全终点、脂质过氧化（血清丙二醛）和 UA 血清动力学。结果 - 24 名中风患者在临床发病后平均 (SD) 133 (35) 分钟内接受 rt-PA 治疗（入院美国国立卫生研究院中风量表评分平均 [SD] 11 [7]，年龄 71 [10.6] 岁，71% 男性）。媒介物组的 UA 水平下降，而高剂量 UA 组的 UA 水平在大约 24 小时内上升，该组在第 5 天的丙二醛水平也较低。3 个治疗组的死亡率 (12.5%)、症状性中枢神经系统出血 (0%) 和第 90 天的结果相似；高剂量组中的一名患者出现轻度痛风发作。 结论 - 在中风发作 3 小时内接受 rt-PA 治疗的患者中，给予 UA 似乎是安全的，可以减少脂质过氧化，并防止血清中 UA 的早期下降。外源性 UA 和 rt-PA 双重给药的临床疗效值得在更大规模的急性卒中试验中进一步研究。
Background and Purpose - Uric acid (UA) increases the neuroprotective effects of recombinant tissue plasminogen activator (rt-PA) in experimental ischemia. In patients with stroke, increased UA levels have been linked to better stroke recovery, but the clinical safety of dual administration of UA and rt-PA is unknown.Methods - Using a double-blind design, we assessed the safety of exogenous UA in patients with acute stroke treated with rt-PA. Patients were randomized to an intravenous solution of 500 mL of 5% mannitol/0.1% lithium carbonate (vehicle group, n = 8) or 500 or 1000 mg of UA (n = 16). Safety end points at day 90, lipid peroxidation (serum malondialdehyde), and serum kinetics of UA were established.Results - Twenty-four patients with stroke were treated with rt-PA within mean (SD) 133 (35) minutes of clinical onset ( admission National Institutes of Health Stroke Scale score mean [SD] 11 [7], age 71 [10.6] years, 71% males). Levels of UA decreased in the vehicle group and increased for approximately 24 hours in the high dose of UA group, which also had lower levels of malondialdehyde at day 5. Mortality (12.5%), symptomatic central nervous system bleeding (0%), and outcome at day 90 were similar in the 3 treatment arms; one patient in the high-dose group had a mild gouty episode.Conclusions - The administration of UA appears to be safe, decreases lipid peroxidation, and prevents an early fall of UA in serum in patients treated with rt-PA within 3 hours of stroke onset. The clinical efficacy of dual administration of exogenous UA and rt-PA deserves further investigation in a larger acute stroke trial.