Published Online
on March 4, 2002

A more recent version of this article appeared on March 26, 2002

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Submitted on October 16, 2001
Revised on December 31, 2001
Accepted on January 16, 2002

Switching off Embolization From Symptomatic Carotid Plaque Using S-Nitrosoglutathione

Zoltan Kaposzta MD, John F. Martin F Med Sci, and Hugh S. Markus FRCP^*

From Clinical Neuroscience, St George's Hospital Medical School (Z.K., H.S.M.), and University College of London (J.F.M.), London, UK.

^* To whom correspondence should be addressed. E-mail: h.markus{at}sghms.ac.uk.

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.

Methods and Results—Twenty patients with 50% internal carotid artery stenosis and with 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.

Key words: ultrasonics • drugs • platelets • carotid arteries • nitric oxide

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