Background and Purpose: The adenosine-regulating agent acadesine has been shown to reduce the incidence of myocardial infarction and stroke after cardiopulmonary bypass surgery. The present study examined the effect of acadesine on the accumulation of indium-labeled platelet emboli and infarct size after photothrombosis of the common carotid artery. Methods: Rats were anesthetized with halothane and pre-loaded with 111In-tropolone-labeled platelets (50 to 80 μCi) 30 minutes before nonocclusive common carotid artery thrombosis induced by a rose bengal-mediated photochemical insult. Intravenous infusion of acadesine (0.5, 1, or 2 mg/kg per minute) or vehicle was begun 30 minutes before right common carotid artery thrombosis and continued for an additional 15 minutes. Rats were then killed and brains processed for the autoradiographic quantitation of labeled platelet aggregates. In a separate group of rats, infarct areas and volumes were determined in treated (acadesine 1 mg/kg per minute) (n=9) and nontreated (n=9) rats 7 days after thrombosis. Results: Although the ratio of right-to- left common carotid artery radioactivity was not affected by treatment, acadesine at 1 and 2 mg/kg per minute significantly decreased (P<.01) platelet deposition within the right cerebral cortex, hippocampus, and striatum. For example, within the frontoparietal cortex, numbers of platelet aggregates were 11.8±1.8 (mean±SEM), 6.1±1.4, 2.3±0.6, and 3.2±0.8 in rats infused with vehicle, 0.5, 1, and 2 mg/kg per minute acadesine, respectively. In addition, infarct volume was reduced by 48% in acadesine- treated (1 mg/kg per minute) rats, with a significant reduction in infarct area at the coronal level 3.7 mm anterior to bregma (P<.01). Conclusions: These results support a prophylactic role for acadesine in reducing the accumulation of platelet emboli during vascular thrombosis and subsequent brain infarction. Acadesine treatment in patients at risk for embolic stroke could potentially lead to cerebral protection.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine