Kaposzta Z, Baskerville P A, Madge D, Fraser S, Martin J F, Markus H S
Clinical Neuroscience, St George's Hospital Medical School, Cranmer Terrace, London.
Circulation. 2001 May 15;103(19):2371-5. doi: 10.1161/01.cir.103.19.2371.
L-Arginine reduces platelet aggregation and adhesion in ex vivo studies, but there is no evidence as yet that it has a therapeutic effect on clinical end points. Doppler ultrasound can detect cerebral emboli noninvasively. Such embolic signals are common after carotid endarterectomy, and their frequency predicts risk of stroke recurrence. We used this situation to determine the antiplatelet efficacy of L-arginine and S-nitrosoglutathione (GSNO), a physiological nitric oxide donor with possible platelet specificity.
Patients undergoing carotid endarterectomy were randomized in a double-blind manner between L-arginine (n=14), GSNO (n=14), or placebo (n=14) administered intravenously for 90 minutes, starting 30 minutes after skin closure. All patients were pretreated with aspirin and given heparin during surgery. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 4 hours after surgery, beginning 30 minutes after skin closure, and also at 6 and 24 hours. There were highly significant reductions in the number of Doppler embolic signals in the L-arginine and GSNO groups; first 4 hours, median (range) number of embolic signals, placebo 44.7 (6 to 778), L-arginine 9.5 (0 to 225), and GSNO 0.8 (0 to 8), both P<0.001 versus control values. The reduction in the signals persisted at the 24-hour recording.
Intravenous L-arginine and GSNO attenuate Doppler embolic signals in humans. Modulation of the NO system with these agents may have applications in the treatment of thromboembolic disease. This study demonstrates the potential application of ultrasonic embolic signal detection to examine the efficacy of new antiplatelet agents in relatively small numbers of patients.
在体外研究中，L-精氨酸可降低血小板聚集和黏附，但尚无证据表明其对临床终点具有治疗作用。多普勒超声可无创检测脑栓塞。此类栓塞信号在颈动脉内膜切除术后很常见，其出现频率可预测中风复发风险。我们利用这种情况来确定L-精氨酸和S-亚硝基谷胱甘肽（GSNO，一种可能具有血小板特异性的生理性一氧化氮供体）的抗血小板疗效。
接受颈动脉内膜切除术的患者在皮肤缝合后30分钟开始，以双盲方式随机分为静脉注射L-精氨酸组（n = 14）、GSNO组（n = 14）或安慰剂组（n = 14），持续90分钟。所有患者术前均接受阿司匹林预处理，术中给予肝素。术后从同侧大脑中动脉进行经颅多普勒记录，记录时间为术后4小时（从皮肤缝合后30分钟开始），以及术后6小时和24小时。L-精氨酸组和GSNO组的多普勒栓塞信号数量显著减少；术后前4小时，栓塞信号数量中位数（范围），安慰剂组为44.7（6至778），L-精氨酸组为9.5（0至225），GSNO组为0.8（0至8），两组与对照组相比P均<0.001。在24小时记录时，信号减少仍持续存在。
静脉注射L-精氨酸和GSNO可减弱人体的多普勒栓塞信号。用这些药物调节一氧化氮系统可能在血栓栓塞性疾病的治疗中具有应用价值。本研究证明了超声栓塞信号检测在相对少数患者中检测新型抗血小板药物疗效的潜在应用。
