Donate Help Contact The AHA Sign In Home
American Heart Association
Stroke
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Stroke. 2004;35:2890-2895
Published online before print October 28, 2004, doi: 10.1161/01.STR.0000147963.68238.da
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
35/12/2890    most recent
01.STR.0000147963.68238.dav1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, L.
Right arrow Articles by Chopp, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, L.
Right arrow Articles by Chopp, M.
Related Collections
Right arrow Embolic stroke
Right arrow Thrombolysis

(Stroke. 2004;35:2890.)
© 2004 American Heart Association, Inc.

Original Contributions

Intravenous Administration of a GPIIb/IIIa Receptor Antagonist Extends the Therapeutic Window of Intra-Arterial Tenecteplase–Tissue Plasminogen Activator in a Rat Stroke Model

Li Zhang, MD; Zheng Gang Zhang, MD, PhD; Chunling Zhang, BS; Rui Lan Zhang, MD Michael Chopp, PhD

From the Department of Neurology (L.Z., Z.G.Z., C.Z., R.Z., M.C.), Henry Ford Health Sciences Center, Detroit, Mich; and the Department of Physics (M.C.), Oakland University, Rochester, Mich.

Correspondence to Dr Michael Chopp, Henry Ford Hospital, Neurology Department, 2799 West Grand Blvd, Detroit, MI 48202. E-mail chopp{at}neuro.hfh.edu

Background and Purpose— Occlusion of the middle cerebral artery triggers platelet accumulation at the site of occlusion and in downstream microvessels. The platelet-induced secondary thrombosis promotes the progressive development of ischemic brain damage and contributes to the resistance to thrombolysis and to the tight 3-hour therapeutic window. We tested the hypothesis that combination of intravenous (IV) administration of a GPIIb/IIIa receptor antagonist, 7E3 F(ab')2, with intra-arterial (IA) administration of tenecteplase–tissue plasminogen activator (TNK-tPA) increases the efficacy of thrombolysis and extends the therapeutic window of stroke.

Methods— Rats subjected to embolic stroke were treated with IV 7E3 F(ab')2 (6 mg/kg) in combination with IA or IV TNK-tPA (5 mg/kg) at 4 and 6 hours after onset of stroke, respectively; IA TNK-tPA (5 mg/kg) alone at 6 hours after onset of stroke; or saline at 6 hours after onset of stroke.

Results— The combination of IV 7E3 F(ab')2 (4 hours) and IA TNK-tPA (6 hours) significantly (P<0.05) reduced infarct volume and improved neurological functional deficits, which was associated with significant (P<0.05) reductions in the size of embolus at the origin of the occluded middle cerebral artery and in down-stream microvascular platelet and fibrin deposition, and enhanced microvascular patency compared with saline-treated rats. However, combination of IV 7E3 F(ab')2 (4 hours) and IV TNK-tPA (6 hours) or IA TNK-tPA (6 hours) alone failed to reduce infarct volume and improve neurological function compared with the saline-treated rats. No significant differences of the incidence of hemorrhage were detected among groups.

Conclusions— These data suggest that the combination of IV 7E3 F(ab')2 (4 hours) and IA TNK-tPA (6 hours) extends the therapeutic window of thrombolysis to 6 hours after stroke.


Key Words: cerebral hemorrhage • cerebral ischemia, transient • thrombolysis • thrombosis




This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. W. Kiessling, D. B. Cines, A. A.-R. Higazi, and W. M. Armstead
Inhibition of integrin {alpha}V{beta}3 prevents urokinase plasminogen activator-mediated impairment of cerebrovasodilation after cerebral hypoxia/ischemia
Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H862 - H867.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
R. L. Zhang, C. Zhang, L. Zhang, C. Roberts, M. Lu, A. Kapke, Y. Cui, M. Ninomiya, T. Nagafuji, B. Albala, et al.
Synergistic Effect of an Endothelin Type A Receptor Antagonist, S-0139, With rtPA on the Neuroprotection After Embolic Stroke
Stroke, October 1, 2008; 39(10): 2830 - 2836.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
R. W. Baumgartner, D. Georgiadis, K. Nedeltchev, G. Schroth, H. Sarikaya, and M. Arnold
Stent-Assisted Endovascular Thrombolysis Versus Intravenous Thrombolysis in Internal Carotid Artery Dissection With Tandem Internal Carotid and Middle Cerebral Artery Occlusion
Stroke, February 1, 2008; 39(2): e27 - e28.
[Full Text] [PDF]

Home page
 StrokeHome page
H. P. Adams Jr, M. B. Effron, J. Torner, A. Davalos, J. Frayne, P. Teal, J. Leclerc, B. Oemar, L. Padgett, E. S. Barnathan, et al.
Emergency Administration of Abciximab for Treatment of Patients With Acute Ischemic Stroke: Results of an International Phase III Trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II)
Stroke, January 1, 2008; 39(1): 87 - 99.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Wang, Z. G. Zhang, R. L. Zhang, S. R. Gregg, A. Hozeska-Solgot, Y. LeTourneau, Y. Wang, and M. Chopp
Matrix metalloproteinase 2 (MMP2) and MMP9 secreted by erythropoietin-activated endothelial cells promote neural progenitor cell migration.
J. Neurosci., May 31, 2006; 26(22): 5996 - 6003.
[Abstract] [Full Text] [PDF]


Stroke Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2004 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.