The effects of a new tissue plasminogen activator analogue, Fb-Fb-CF, on cerebral reperfusion in a rabbit embolic stroke model.
Early fibrinolytic therapy with full molecular tissue plasminogen activator (t-PA) has been observed to be both angiographically and clinically effective when employed in animal stroke models. Preliminary clinical trials with t-PA are in progress. It is possible to refine t-PA by developing fragments or analogues of the drug. Using recombinant DNA technology in the Escherichia coli system, a t-PA analogue consisting of the catalytic fragment of t-PA and a dimer of the B fragment of staphylococcal protein A (Fb-Fb-CF) has been produced. Because this analogue has a long serum half-life of 90 minutes, we employed Fb-Fb-CF in a rabbit cerebral embolic stroke model to assess its efficacy as a reperfusion agent. When given as a bolus to 10 animals 15 minutes after embolization, Fb-Fb-CF produced angiographic cerebral reperfusion in 48 +/- 21 minutes (+/- SD), while in 8 saline-treated controls, reperfusion was not observed at 180 minutes in any animal (p less than 0.01). In another experiment reperfusion was demonstrated at 66 +/- 32 minutes in 11 animals treated with Fb-Fb-CF 90 minutes after embolization as compared with 100 +/- 25 minutes in 12 saline-treated controls (p less than 0.01). A small macroscopic hemorrhage within an infarct was seen in 1 Fb-Fb-CF-treated animal in the 15-minute experiment and in none of the controls. In the 90-minute experiment, macroscopic hemorrhagic infarction was seen in 4 Fb-Fb-CF-treated animals and in 3 controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Phillips
D A
DA
Department of Radiology, University of Massachusetts Medical School, Worcester.
Fisher
M
M
Smith
T W
TW
Davis
M A
MA
Pang
R H
RH
D000818:Animals; D002543:Cerebral Hemorrhage / Q000209:etiology; D002561:Cerebrovascular Disorders / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D010446:Peptide Fragments / Q000627:therapeutic use*; D011817:Rabbits; D015424:Reperfusion; D013205:Staphylococcal Protein A / Q000627:therapeutic use*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D010446:Peptide Fragments; D013205:Staphylococcal Protein A; D010959:Tissue Plasminogen Activator; C059835:tissue plasminogen activator-(staphylococcal A, B fragment) dimer