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(Stroke. 1995;26:111-116.)
© 1995 American Heart Association, Inc.

Articles

Acadesine Reduces Indium-Labeled Platelet Deposition After Photothrombosis of the Common Carotid Artery in Rats

W. Dalton Dietrich, PhD; Leonard P. Miller, PhD; Ricardo Prado, MD; Sumit Dewanjee, BS; Nancy Alexis, MS; Mrinal K. Dewanjee, PhD Harry Gruber, MD

From the Departments of Neurology (W.D.D., R.P., N.A.) and Radiology (S.D., M.K.D.), University of Miami (Fla) School of Medicine, and Gensia Pharmaceuticals, Inc (L.P.M., H.G.), San Diego, Calif.

Correspondence to W. Dalton Dietrich, PhD, Department of Neurology (D4-5), University of Miami, School of Medicine, PO Box 016960, Miami, FL 33101.

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 preloaded 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.

Key Words: adenosine • embolism • neuroprotection • thrombosis • rats

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