ACADESINE REDUCES INDIUM-LABELED PLATELET DEPOSITION AFTER PHOTOTHROMBOSIS OF THE COMMON CAROTID-ARTERY IN RATS

Background and Purpose The adenosine-regulating agent acadesine has be en shown to reduce the incidence of myocardial infarction and stroke a fter cardiopulmonary bypass surgery. The present study examined the ef fect of acadesine on the accumulation of indium-labeled platelet embol i and infarct size after photothrombosis of the common carotid artery. Methods Rats were anesthetized with halothane and preloaded with In-1 11-tropolone-labeled platelets (50 to 80 mu Ci) 30 minutes before nono cclusive common carotid artery thrombosis induced by a rose bengal-med iated photochemical insult. Intravenous infusion of acadesine (0.5, 1, or 2 mg/kg per minute) or vehicle was begun 30 minutes before right c ommon a carotid artery thrombosis and continued for an additional 15 m inutes. Rats were then killed and brains processed for the autoradiogr aphic quantitation of labeled platelet aggregates. In a separate group of rats, infarct areas and volumes were determined in treated (acades ine 1 mg/kg per minute) (n=9) and nontreated (n=9) rats 7 days after t hrombosis. 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 depositio n within the right cerebral cortex hippocampus, and striatum. For exam ple, 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 r ats infused with vehicle, 0.5,, 1, and 2 mg/kg per minute acadesine, r espectively. In addition, infarct volume was reduced by 48% in acadesi ne-treated (1 mg/kg per minute) rats, with a si,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 thromb osis and subsequent brain infarction. Acadesine treatment in patients at risk for embolic stroke could potentially lead to cerebral protecti on.