l -Arginine and S -Nitrosoglutathione Reduce Embolization in Humans

Abstract

Intravenous L-arginine and GSNO attenuate Doppler embolic signals in humans. Modulation of the NO system with these agents may have applications in the treatment of thromboembolic disease. This study demonstrates the potential application of ultrasonic embolic signal detection to examine the efficacy of new antiplatelet agents in relatively small numbers of patients.

The von Willebrand Inhibitor ARC1779 Reduces Cerebral Embolization After Carotid Endarterectomy

“…This setting has been used to show the efficacy of aspirin and clopidogrel 14 and GSNO, a novel nitric oxide inhibitor. 15 The results found correlated well with those in subsequent studies in symptomatic carotid stenosis. 4,16 Therefore, we evaluated the efficacy of ARC1779 in reducing embolization in the immediate postoperative phase after CEA.…”

“…ES intensity is proportional to embolus size, 20 ; previous studies have shown a reduction in ES intensity parallels a reduction in ES frequency and therapeutic efficacy. 4,6,15,16 Phase 1 studies suggested ARC1779 inhibited platelet aggregation without a significant increase in bleeding. 9 This study, in patients undergoing operation, showed an increased bleeding risk with ARC1779.…”

“…Considering the major secondary end point, total ES count in a 3-hour observation period, it was assumed that the expected mean count in the controls with nonzero counts was 15 based on published data. 14,15 It was assumed treatment with ARC1779 would reduce ES count by 33% to a mean of 10. Twenty-four subjects per group was expected to give 80% power to detect a difference at 5% level (2-sided).…”

“…12,13 The ES are believed to represent platelet aggregates and this is supported by studies showing their frequency can be markedly reduced by antiplatelet agents. 14,15 Because of the large number of ES, antiplatelet efficacy can be evaluated in relatively small patient numbers. This setting has been used to show the efficacy of aspirin and clopidogrel 14 and GSNO, a novel nitric oxide inhibitor.…”

Assessment: Transcranial Doppler ultrasonography: [RETIRED]

“…61,66 TCD may also be used to noninvasively monitor the effect of novel antiplatelet agents on the frequency of microembolic signals following CEA. 67 CEA monitoring with TCD can provide important feedback pertaining to hemodynamic and embolic events during and after surgery that may help the surgeon take appropriate measures at all stages of the operation to reduce the risk of perioperative stroke. TCD monitoring is probably useful during and after CEA in circumstances where monitoring is felt to be necessary (Type B, Class II to III evidence).…”