Switching off embolization from symptomatic carotid plaque using S-nitrosoglutathione.
BACKGROUND
Current antiplatelet regimens fail to prevent the majority of recurrent strokes. Asymptomatic circulating emboli can be detected by transcranial Doppler ultrasound, are frequent in patients with symptomatic carotid stenosis, and predict recurrent stroke risk. S-nitrosoglutathione (GSNO) is a nitric oxide donor that appears to have relative platelet specificity. We evaluated its effectiveness in reducing embolization in patients with symptomatic carotid stenosis who already were taking aspirin.


RESULTS
Twenty patients with > or =50% internal carotid artery stenosis and with > or =3 embolic signals detected during a half-hour screening recording were recruited. All had taken aspirin for at least 7 days. They were randomly assigned in a double-blind fashion to either GSNO (4.4 mmol/kg per minute) or saline placebo for 90 minutes. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 1 hour before treatment and at 0 to 3, 6, and 24 hours after treatment. Before treatment, the mean (range) of embolic signals per hour was 6.9 (3 to 13) in the GSNO group and 7.3 (4 to 12) in the placebo group (P=0.68). GSNO resulted in a rapid reduction in the frequency of embolic signals of 84% at 0 to 3 hours, 95% at 6 hours, and 100% at 24 hours (P<0.0001, P=0.003, and P<0.0001 versus placebo, respectively).


CONCLUSIONS
Continued embolization is common in patients with carotid stenosis despite aspirin therapy. GSNO was highly effective in rapidly reducing the frequency of embolic signals in this patient group. Despite its short administration time and its short half-life, it resulted in therapeutic effects lasting 24 hours.
Kaposzta
Zoltan
Z
Clinical Neuroscience, St George's Hospital Medical School, London, UK.
Martin
John F
JF
Markus
Hugh S
HS
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D002340:Carotid Artery Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D020766:Intracranial Embolism / Q000000981:diagnostic imaging / Q000517:prevention & control*; D008297:Male; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D026422:S-Nitrosoglutathione / Q000627:therapeutic use*; D055502:Secondary Prevention; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial
D010975:Platelet Aggregation Inhibitors; D026422:S-Nitrosoglutathione; D001241:Aspirin