The effect of vasodilators on aspirin-induced antagonism of t-PA thrombolysis
| Autor: | Martin M. Bednar, Sheila R. Russell, Cordell E. Gross, Carolyn Ellenberger, Diantha B. Howard |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Vasodilator Agents medicine.medical_treatment Thromboembolic stroke Nitric Oxide Brain Ischemia Fibrinolytic Agents Thromboembolism Prostaglandins Synthetic medicine Animals Drug Interactions Nitric Oxide Donors Thrombolytic Therapy Stroke Antihypertensive Agents Aspirin business.industry General Medicine Thrombolysis Hydralazine Atenolol medicine.disease Treatment Outcome Neurology Cerebrovascular Circulation Tissue Plasminogen Activator Anesthesia Drug Therapy Combination Female Rabbits Neurology (clinical) Antagonism business Adjuvant medicine.drug |
| Zdroj: | Neurological Research. 23:745-750 |
| ISSN: | 1743-1328 0161-6412 |
| DOI: | 10.1179/016164101101199117 |
| Popis: | Although i.v. t-PA has proven successful in reducing neurologic deficits in acute ischemic stroke, the disadvantages of a narrow therapeutic time window and the failure of thrombolysis in more than 50% of patients treated have necessitated an examination of adjuvant therapies to improve the rate of thrombolysis. Experimentally, the combination of aspirin therapy with t-PA has resulted in a paradoxical antagonism of thrombolysis. Reversal of this antagonism with nitric oxide (NO) donors suggested that aspirin may inhibit/ antagonize NO-related mechanisms. Using this rabbit model of thromboembolic stroke, this hypothesis is now expanded to compare two clinically relevant anti-hypertensive agents, atenolol (NO-dependent) and hydralazine (NO-independent), for their ability to improve t-PA-mediated clot lysis following aspirin pre-treatment. Thirty rabbits (10 per group) were pre-treated with aspirin (20mg kg(-1), i.v.) and then randomized to receive either vehicle, atenolol (20 microg kg(-1) h(-1), i.v.) or hydralazine (10 microg kg(-1) min(-1), i.v.) beginning 30 min following autologous clot embolization. All rabbits then received t-PA (6.3 mg kg(-1), i.v.) beginning 1 h after embolization, with completion of the protocol 4 h after embolization. Aspirin therapy reduced regional cerebral blood flow (rCBF) from 82.8m +/- 4.7 to 62.5 +/- 6.6 (n = 30; p = 0.0005). In the aspirin control group only 30% (3 of 10) rabbits demonstrated complete clot lysis, whereas the combined atenolol (60%) and hydralazine (70%) groups experienced a clot lysis rate of 65% (13 of 20 rabbits), similar to clot lysis rates previously observed with t-PA alone. In a separate series of experiments, all agents able to reverse aspirin antagonism of thrombolysis demonstrated an improvement in rCBF, suggesting a common mechanism for this diverse group of agents in reversing aspirin's antagonism of thrombolysis. |
| Databáze: | OpenAIRE |
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