Authors: Lu, Aigang; Kurosawa, Yuko; Luskey, Kenneth; Pyne-Geithman, Gail; Caudell, Danielle; Clark, Joseph

Source: Neurological Research, Volume 31, Number 2, March 2009 , pp. 209-214(6)

Publisher: Maney Publishing

Abstract:

Objective: Recanalization therapies for ischemic stroke have been slow to change clinical practice because of perceived and published risks of hemorrhage associated with lytic administration. We quantified alfimeprase in an acute ischemia?reperfusion model, as compared with recombinant tissue plasminogen activator, with hemorrhagic transformation as the primary endpoint and infarction volume and blood?brain barrier permeability as secondary endpoints.

Methods: Five groups were studied in a blinded fashion: alfimeprase at doses of 0.03 (n=8), 0.1 (n=11) and 0.3 mg/kg (n=8); recombinant tissue plasminogen activator at 1 mg/kg (n=9); carrier infused controls (n=9). The middle cerebral artery was occluded for 5 hours followed by removal of the suture for reperfusion. Drugs were infused immediately following reperfusion over a 10-minute period. Approximately 24 hours later, the animals were anesthetized and decapitated, and the brains were rapidly harvested and frozen. Serial brain sections were obtained and inspected for hemorrhages. Infarction and blood?brain barrier permeability were also evaluated in additional experiments in control, 0.1 mg/kg alfimeprase and 1 mg/kg recombinant tissue plasminogen activator-treated rats.

Results: The hemorrhagic transformation frequency, neurological deficit and the mortality rate of alfimeprase were significantly lower than for recombinant tissue plasminogen activator at the 0.03 mg/kg dose and not statistically different at the higher doses. Infarction and blood?brain barrier permeability were not significantly different among control, 0.1 mg/kg alfimeprase and recombinant tissue plasminogen activator.

Discussion: In this model, alfimeprase, a new fibrinolytic agent, exhibits a profile comparable to recombinant tissue plasminogen activator.

Keywords: CEREBRAL ISCHEMIA; INFARCTION; BLOOD-BRAIN BARRIER PERMEABILITY; ALFIMEPRASE; HEMORRHAGIC TRANSFORMATION

Document Type: Research Article

DOI: http://dx.doi.org/10.1179/174313209X393933

Affiliations: Department of Neurology, Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH, USA

Publication date: 2009-03-01

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