6145
document
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 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 . METHODS AND RESULTS 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 . CONCLUSIONS 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 .
6146
Intervention_Pharmacological
L-arginine
6147
Intervention_Pharmacological
S-nitrosoglutathione
6148
Intervention_Pharmacological
L-Arginine
6149
Intervention_Pharmacological
L-arginine
6150
Intervention_Pharmacological
S-nitrosoglutathione ( GSNO )
6151
Intervention_Pharmacological
L-arginine
6152
Intervention_Pharmacological
GSNO
6153
Intervention_Control
placebo
6154
Intervention_Pharmacological
aspirin
6155
Intervention_Pharmacological
heparin
6156
Intervention_Pharmacological
L-arginine
6157
Intervention_Pharmacological
GSNO
6158
Intervention_Pharmacological
L-arginine
6159
Intervention_Pharmacological
GSNO
6160
Intervention_Pharmacological
L-arginine
6161
Intervention_Pharmacological
GSNO
6162
Outcome_Physical
embolization
6163
Outcome_Physical
platelet aggregation and adhesion
6164
Outcome_Other
antiplatelet efficacy
6165
Outcome_Physical
number of Doppler embolic signals in the L-arginine and GSNO
6166
Outcome_Physical
number of embolic signals
6167
Outcome_Other
reduction in the signals
6168
Outcome_Physical
attenuate Doppler embolic signals
6169
Participant_Condition
undergoing carotid endarterectomy