Combination treatment with dipyridamole, aspirin, and tPA in an embolic model of stroke in rats.
Antithrombotic therapy has been shown to be effective in preventing secondary strokes. Inhibition of platelet function may reduce formation of thrombi thereby reducing the incidence of stroke. However, stronger inhibition of platelets is correlated with increased risk of bleeding events. The purpose of this study was to test the protective effects of combination therapy with dipyridamole and acetylsalicylic acid (ASA) in comparison to ASA alone, and whether such combination treatment may produce any added benefits when tissue plasminogen activator (tPA) treatment is also used. The study was divided into three parts. In part A, effect of antiplatelets on infarct volume was assessed. In part B, perfusion deficits were measured. In part C, efficacy of antiplatelet therapy in combination with tPA was assessed. In part A, dipyridamole and aspirin treatment significantly reduced infarct volume (P<0.05). In part B, treatment with dipyridamole significantly reduced the perfusion deficits as compared to control (P<0.05). In part C, dipyridamole plus tPA or dipyridamole and aspirin plus tPA significantly decreased infarct volume as compared to tPA alone (P<0.05). The present study suggests that there is significant protection with dipyridamole as both infarct volume and perfusion deficits are significantly reduced. Dipyridamole with tPA also significantly reduced infarct volume as compared to tPA alone. Our data suggests that higher doses of antithrombotic therapy with dipyridamole offer best neuroprotection.
Aldandashi
Samer
S
Stroke Research Laboratory, University of Alberta, 533 HMRC, Edmonton, Alberta, Canada T6G 2S2.
Noor
Raza
R
Wang
Chen Xu
CX
Uddin
Ghias
G
Shuaib
Ashfaq
A
D000818:Animals; D001241:Aspirin / Q000097:blood / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004176:Dipyridamole / Q000097:blood / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D020766:Intracranial Embolism / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology*; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D010959:Tissue Plasminogen Activator; D001241:Aspirin