From the Department of Clinical Neuroscience (J.M., H.S.M.), King's
College School of Medicine and Dentistry and Institute of Psychiatry;
Department of Cardiovascular Medicine (J.F.M.), University College Medical
School; and Department of Vascular Surgery (P.A.B., S.C.A.F.), King's
College Hospital, London, UK.
Correspondence to Dr Hugh Markus, Department of Neurology, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK. E-mail h.markus{at}iop.bpmf.ac.uk
Background—Antiplatelet
agents presently used in the secondary prevention of
cardiovascular disease fail to prevent the
majority of cases of recurrent stroke and systemic embolization. An
evaluation of the efficacy of new agents is hampered by a lack of in
vivo models in humans. Asymptomatic cerebral embolic
signals (ES) may be detected with the use of transcranial
Doppler ultrasonography. These signals are particularly common
after carotid endarterectomy, and this provides a
situation in which new antiplatelet agents can be evaluated. With
this model, we determined the effectiveness of
S-nitrosoglutathione (GSNO), a nitric oxide donor with
relative platelet specificity, in reducing cerebral
embolization.
Methods and Results—Transcranial Doppler
ultrasound recordings from the ipsilateral middle cerebral
artery were made after carotid endarterectomy in 12
control patients and 12 patients receiving intravenous GSNO
from the induction of anesthesia until 2 hours after skin
closure. Recording times were 0.5 to 3.5, 6 to 7, and 24 to 25
hours after skin closure. The Doppler signal was recorded onto
tape, and analysis for ES was performed, with the investigators
blinded to treatment group. All patients received aspirin 300 mg/d
before surgery and 5000 IU of heparin during surgery. The median
(range) number of ES detected during the initial 3-hour postoperative
recording was markedly reduced in the GSNO group compared with
the control group: 7.5 (0 to 61) versus 38.5 (1 to 219)
(P=0.018). This difference persisted until 6 hours after
surgery.
Conclusions—Despite the administration of aspirin and heparin,
frequent embolization occurred and was markedly reduced after the
administration of GSNO. This demonstrates the potential use of
platelet-specific nitric oxide donors in the treatment of
thromboembolic disease. This model of cerebral embolism may allow
determination of the effectiveness of new antiplatelet agents in
humans.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
S-Nitrosoglutathione Reduces the Rate of Embolization in Humans
Key Words: ultrasonics • drugs • platelet aggregation inhibitors • endothelium-derived factors
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