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Invited Symposium: Cerebral Artery Pharmacology and Physiology






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Aspirin Antagonism Of t-PA Thrombolysis In A Rabbit Model Of Thromboembolic Stroke Is Associated With A Reduction In Cerebral Blood Flow

Bednar, MM (University of Vermont, USA)
Gross, CE (University of Vermont, USA)

Contact Person: Martin M. Bednar (mbednar@zoo.uvm.edu)


Abstract

BACKGROUND: Aspirin therapy for stroke prophylaxis in low risk patients has paradoxically demonstrated an increased risk of ischemic stroke in several studies. Moreover, the MAST-Italy trial reported a near doubling of mortality with the addition of aspirin to thrombolytics while experimentally, we have noted that aspirin antagonizes t-PA-mediated clot lysis. The mechanisms responsible for these observations is unclear. Of interest, few studies have examined the effect of aspirin on cerebral blood flow (CBF).
OBJECTIVE: To examine the acute effect of high dose aspirin on CBF in a rabbit model.
METHODS: Mean arterial pressure, arterial blood gases, and core and brain temperature were controlled throughout the protocol. CBF, measured by the technique of hydrogen clearance using Platinum-Iridium flow probes, was measured before and 20 minutes following aspirin administration (20 mg/kg, i.v.) in a cohort of 50 rabbits and compared to rabbits receiving vehicle (n=19).
RESULTS: Following aspirin therapy, CBF (cc/100gm/min) was reduced from 80.8 27.4 to 65.1 31.7 (mean S.D.), a reduction to 80.4 21.3% of baseline (P < 0.00001, t-test), whereas CBF in the control group remained unchanged (81.0 25.4 vs 77.5 24.0, mean S.D.).
CONCLUSION: Aspirin acutely reduced CBF by approximately 20% in a rabbit model, perhaps related to inhibitory effects on prostacyclin and/or nitric oxide. This result may help explain the possible increase in ischemic stroke seen in low risk patients on aspirin therapy. A reduction in CBF by aspirin may also assist in understanding the antagonism of t-PA-mediated clot lysis by aspirin seen in our rabbit model of thromboembolic stroke, particularly since all agents which share the ability to reverse this antagonism (nitric oxide donors, beta blockers, hydralazine, prostacyclin) also increase CBF by approximately 20%. Future strategies for "antiplatelet" therapy may benefit from using agents which do not adversely affect CBF.

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Presentation Number SAbednar0908
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Bednar, MM; Gross, CE; (1998). Aspirin Antagonism Of t-PA Thrombolysis In A Rabbit Model Of Thromboembolic Stroke Is Associated With A Reduction In Cerebral Blood Flow. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/laher/bednar0908/index.html
© 1998 Author(s) Hold Copyright