Protective effects of pamiteplase, a modified t-PA, in a rat model of embolic stroke.
The effects of alteplase (tissue plasminogen activator, t-PA) and pamiteplase (a modified t-PA with longer half-life and increased potency) were compared in a clinically relevant model of embolic stroke. Rats were treated with pamiteplase (0.5 mg/kg or 1 mg/kg bolus), alteplase (10 mg/kg infusion) or normal saline. Pamiteplase (1 mg/kg) was as effective as alteplase in reducing 24 h brain infarct volumes, neurological deficit scores and residual clot grades. Cerebral blood flow recovery at 30 min after thrombolytic treatment was partial and did not correlate with 24 h infarct volumes or neurological deficits. However, there was good correlation between 24 h residual clot grades and infarct volumes, suggesting a delayed timeframe for pamiteplase- and alteplase-induced reperfusion.
Department of Neurology, Massachusetts General Hospital, Charlestown 02129, USA.
T
T
Sumii
A B
AB
Singhal
M
M
Asahi
M
M
Shimizu-Sasamata
M
M
Suzuki
K
K
Miyata
E H
EH
Lo
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D020766:Intracranial Embolism / Q000188:drug therapy*; D017078:Laser-Doppler Flowmetry; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology*; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; C085027:pamiteplase