title: Intraarterial reteplase and intravenous abciximab for treatment of acute ischemic stroke. A preliminary feasibility and safety study in a non-human primate model.
abstract: 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.
authors.affiliation: Zeenat Qureshi Stroke Research Center, The University of Medicine and Dentistry of New Jersey, DOC 8100, 90 Bergen Street, Newark, NJ 07103, USA. qureshai@umdnj.edu
authors.forename: Adnan I
authors.initials: AI
authors.lastname: Qureshi
authors.forename: M Fareed K
authors.initials: MF
authors.lastname: Suri
authors.forename: Zulfiqar
authors.initials: Z
authors.lastname: Ali
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ringer
authors.forename: Alan S
authors.initials: AS
authors.lastname: Boulos
authors.forename: Marian T
authors.initials: MT
authors.lastname: Nakada
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Alberico
authors.forename: Lisa B E
authors.initials: LB
authors.lastname: Martin
authors.forename: Lee R
authors.initials: LR
authors.lastname: Guterman
authors.forename: L Nelson
authors.initials: LN
authors.lastname: Hopkins
mesh_terms: D000077284:Abciximab; D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D015552:Injections, Intralesional; D020767:Intracranial Thrombosis / Q000188:drug therapy*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C087896:reteplase; D010959:Tissue Plasminogen Activator; D000077284:Abciximab