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S-nitrosoglutathione reduces the rate of embolization in humans.

Abstract：

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.

journal_name

Circulation

journal_title

Circulation

authors

Molloy J,Martin JF,Baskerville PA,Fraser SC,Markus HS

doi

10.1161/01.cir.98.14.1372

subject

Has Abstract

pub_date

1998-10-06 00:00:00

pages

1372-5

issue

eissn

0009-7322

issn

1524-4539

journal_volume

pub_type

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S-nitrosoglutathione reduces the rate of embolization in humans.