Intraarterial reteplase and intravenous abciximab for treatment of acute ischemic stroke
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We performed a preliminary feasibility and safety study using intravenous (IV) administration of a platelet glycoprotein IIb/IIIa inhibitor (abciximab) in conjunction with intraarterial (IA) administration of a thrombolytic agent (reteplase) in a primate model of intracranial thrombosis. We introduced thrombus through superselective catheterization of the intracranial segment of the internal carotid artery in 16 primates. The animals were randomly assigned to receive IA reteplase and IV abciximab ( n =4), IA reteplase and IV placebo ( n =4), IA placebo and IV abciximab ( n =4) or IA and IV placebo ( n =4). Recanalization was assessed by serial angiography during the 6-h period after initiation of treatment. Postmortem magnetic resonance (MR) imaging was performed to determine the presence of cerebral infarction or intracranial hemorrhage. Partial or complete recanalization at 6 h after initiation of treatment (decrease of two or more points in pre-treatment angiographic occlusion grade) was observed in two animals treated with IA reteplase and IV abciximab, three animals treated with IA reteplase alone and one animal treated with IV abciximab alone. No improvement in perfusion was observed in animals that received IV and IA placebo. Cerebral infarction was demonstrated on postmortem MR imaging in three animals that received IA and IV placebo and in one animal each from the groups that received IA reteplase and IV abciximab or IV abciximab alone. One animal that received IV abciximab alone had a small intracerebral hemorrhage on MR imaging. IA reteplase with or without abciximab appeared to be the most effective regimen for achieving recanalization in our model of intracranial thrombosis. Further studies are required in experimental models to determine the optimal dose, method of administration and efficacy of these medications in acute ischemic stroke.
KeywordsAntiplatelet agents Ischemic stroke Magnetic resonance imaging Primates Thrombolysis
The study was supported by a grant from Centocor, Inc. The company assisted in the study design, interpretation of data and the writing and approval of the report.
- 13.Ringer AJ, Guterman LR, Hopkins L N (2001) Site-specific thromboembolism: A novel animal model for stroke. 50th Annual Meeting of the Congress of Neurological Surgeons, San Antonio, TexasGoogle Scholar
- 15.Neuhaus KL, von Essen R, Vogt A, et al (1994) Dose finding with a novel recombinant plasminogen activator (BM 06.022) in patients with acute myocardial infarction: results of the German Recombinant Plasminogen Activator Study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte (ALKK). J Am Coll Cardiol 24:55–60PubMedGoogle Scholar
- 20.Boehringer Mannheim GmbH. Retavase-reteplase recombinant (1997) Product monographGoogle Scholar
- 31.Harrington RA, Ohman EM, Sigmon KN, et al (1995) Intensity of inhibition of the platelet glycoprotein IIb/IIIa receptor differs among disease states. Circulation 92 [Suppl I]:I-488–I-489Google Scholar
- 33.Kleiman NS, Raizner AE, Jordan R, et al (1995) Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: implications for inhibition of the internal pool of GPIIb/IIIa receptors. J Am Coll Cardiol 26:1665–1671CrossRefPubMedGoogle Scholar