L-arginine and S-nitrosoglutathione reduce embolization in humans

Background-L-Arginine reduces platelet aggregation and adhesion in ex vivo studies, but there is no evidence as yet that it has a therapeutic effect o n clinical end points. Doppler ultrasound can detect cerebral emboli noninv asively. 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-nitrosoglutathio ne (GSNO), a physiological nitric oxide donor with possible platelet specif icity. Methods and Results-Patients undergoing carotid endarterectomy were randomi zed in a double-blind manner between L-arginine (n = 14), GSNO (n = 14), or placebo (n = 14) administered intravenously for 90 minutes, starting 30 mi nutes after skin closure. All patients were pretreated with aspirin and giv en heparin during surgery. Transcranial Doppler recordings were made from t he ipsilateral middle cerebral artery for 4 hours after surgery, beginning 30 minutes after skin closure, and also at 6 and 24 hours. There were highl y significant reductions in the number of Doppler embolic signals in the L- arginine and GSNO groups; first 4 hours, median (range) number of embolic s ignals, 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 p ersisted at the 24-hour recording. Conclusions-Intravenous L-arginine and GSNO attenuate Doppler embolic signa ls in humans. Modulation of the NO system with these agents may have applic ations 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 pat ients.