Antiplatelet Loading Improves Behavioral Outcome in a Rabbit Model of Stroke

Abstract

No approved acute therapy exists for thousands of patients with ischemic stroke who present ineligible for thrombolytics. The purpose of this proof-of-concept study was to evaluate the efficacy of acute antiplatelet loading on stroke outcome in the rabbit small clot embolic model. Sixty male New Zealand white rabbits were embolized via small clots into the middle cerebral artery. Two hours later, animals were treated with (1) aspirin (5 mg/kg; n=20); (2) usual dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 10 mg/kg; n=20); or (3) high-dose dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 30 mg/kg; n=20). The coprimary outcomes were as follows: (1) platelet inhibition and (2) behavioral outcome as measured by the P50 (milligrams of clot that leads to neurological dysfunction in 50% of animals in a group). There was a significant difference in 3-hour arachidonic acid and ADP (P<0.011); 6-hour collagen and ADP (P<0.01, P<0.01); and 24-hour collagen, arachidonic acid, and ADP (P=0.02, P<0.01, P<0.01) platelet inhibition. The behavioral outcome was significantly better in the usual dual antiplatelet loading versus aspirin group (P=0.02). This study suggests that usual dual antiplatelet loading is clinically beneficial in a validated model of acute stroke. Study of usual dual antiplatelet loading in acute stroke is warranted to provide treatment to stroke victims ineligible for current therapies.