Abstract 8734: Loading of Aspirin and Clopidogrel: Effect of Dose on Stroke Outcome in the Rabbit Small Clot Embolic Model
Background and Purpose: No acute therapy exists for the hundreds of thousands of ischemic stroke patients who present ineligible for thrombolytic treatment. The purpose of this proof of concept study was to evaluate the dose-dependent efficacy of acute, high-dose, antiplatelet loading on stroke outcome in the rabbit small clot embolic model (RSCEM).
Methods: Sixty male New Zealand White rabbits were embolized by injecting small blood clots into the middle cerebral artery via an internal carotid artery catheter. Two hours after embolization, rabbits were treated with either: 1) aspirin (ASA) (5mg/kg); 2) standard loading (SD) (aspirin10mg/kg plus clopidogrel 10mg/kg); or 3) high dose loading (HD) (aspirin 10mg/kg plus clopidogrel 30mg/kg). The co-primary outcome measures were: 1) inhibition of platelet aggregation in response to collagen, arachadonic acid (AA), and adenosine diphosphate (ADP) at 3, 6, and 24 hours and 2) behavioral outcome as measured by the P50 (milligram amount of clot that leads to neurologic dysfunction in 50% of animals in a group) at 24 hours.
Results: ANOVA showed a significant difference among groups in 3 hour AA and ADP platelet inhibition (p<0.011); 6 hour collagen and ADP platelet inhibition (p<0.011; p<0.011); and 24 hour collagen, AA, and ADP platelet inhibition (p=0.02; p<0.011; p<0.011). Six hour platelet inhibition in response to collagen (p<0.01) was significantly increased in SD as compared to the ASA group, yet significantly lower in ADP response than the HD group (p<0.01). Twenty-four hour platelet inhibition in response to all reagents was significantly increased in SD vs ASA groups (collagen p=0.01; AA p<0.01), although response to AA and ADP was significantly less in SD as compared to HD (p<0.013; p = <0.05, respectively). The behavioral outcome of the P50 was significantly better in the SD vs ASA group (p=0.028).
Conclusions: This study suggests that standard dose antiplatelet loading is clinically beneficial in a validated model of acute stroke. A clinical trial of standard dose antiplatelet loading in acute stroke is warranted to provide treatment to the large group of stroke victims ineligible for current therapies.
- © 2010 by American Heart Association, Inc.