S-NITROSOGLUTATHIONE REDUCES THE RATE OF EMBOLIZATION IN HUMANS

Background-Antiplatelet agents presently used in the secondary prevent ion of cardiovascular disease fail to prevent the majority of cases of recurrent stroke and systemic embolization. An evaluation of the effi cacy of new agents is hampered by a lack of in vivo models in humans. Asymptomatic cerebral embolic signals (ES) may be detected with the us e of transcranial Doppler ultrasonography. These signals an particular ly 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 reco rdings from the ipsilateral middle cerebral artery were made after car otid endarterectomy in 12 control patients and 12 patients receiving i ntravenous GSNO from the induction of anesthesia until 2 hours after s kin closure. Recording times were 0.5 to 3.5, 6 to 7, and 24 to 25 hou rs after skin closure. The Doppler signal was recorded onto tape, and analysis for ES was performed, with the investigators blinded to treat ment group. All patients received aspirin 300 mg/d before surgery and 5000 IU of heparin during surgery. The median (range) number of ES det ected during the initial 3-hour postoperative recording was markedly r educed 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 thromboem bolic disease. This model of cerebral embolism may allow determination of the effectiveness of new antiplatelet agents in humans.