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https://hdl.handle.net/2440/10459
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Type: | Journal article |
Title: | Integrin αIIbβ3 inhibitor preserves microvascular patency in experimental acute focal cerebral ischemia |
Other Titles: | Integrin alphaIIb beta3 inhibitor preserves microvascular patency in experimental acute focal cerebral ischemia |
Author: | Abumiya, T. Fitridge, R. Mazur, C. Copeland, B. Koziol, J. Tschopp, J. Pierschbacher, M. del Zoppo, G. |
Citation: | Stroke, 2000; 31(6):1402-1410 |
Publisher: | Lippincott Williams & Wilkins |
Issue Date: | 2000 |
ISSN: | 0039-2499 1524-4628 |
Statement of Responsibility: | Takeo Abumiya, Robert Fitridge, Curt Mazur, Brian R. Copeland, James A. Koziol, Juerg F. Tschopp, Michael D. Pierschbacher, Gregory J. del Zoppo, and Patricia D. Hurn |
Abstract: | <h4>Background and purpose</h4>Platelets become activated and accumulate in brain microvessels of the ischemic microvascular bed after experimental focal cerebral ischemia. The binding of glycoprotein IIb/IIIa (integrin alpha(IIb)beta(3)) on platelets to fibrinogen is the terminal step in platelet adhesion and aggregation. This study tests the hypothesis that inhibition of platelet-fibrin(ogen) interactions may prevent microvascular occlusion after experimental middle cerebral artery occlusion (MCA:O).<h4>Methods</h4>TP9201 is a novel Arg-Gly-Asp (RGD)-containing integrin alpha(IIb)beta(3) inhibitor. Microvascular patency after 3-hour MCA:O and 1-hour reperfusion within the ischemic and nonischemic basal ganglia was compared in adolescent male baboons who received high-dose TP9201 (group A: IC(80) in heparin, n=4), low-dose TP9201 (group B: IC(30) in heparin, n=4), or no treatment (group C: n=4) before MCA:O.<h4>Results</h4>After MCA:O, microvascular patency decreased significantly in group C. However, in the ischemic zones of groups A and B compared with group C, patencies were significantly greater in the 4.0- to 7. 5-microm-diameter (capillary) and 7.5- to 30.0-microm-diameter vessels (2P<0.05). A dose-dependent increase in hemorrhagic transformation was seen in group A (3 of 4 animals) compared with group B (1 of 4 animals), and no hemorrhage was visible in group C (chi(2) analysis for trend, P<0.05).<h4>Conclusions</h4>Platelet activation contributes significantly to ischemic microvascular occlusion. Occlusion formation may be prevented by this RGD-integrin alpha(IIb)beta(3) inhibitor at a dose that does not produce clinically significant parenchymal hemorrhage. The effect of microvascular patency on neuron recovery can now be tested. |
Keywords: | Microcirculation Basal Ganglia Animals Papio Brain Ischemia Infarction, Middle Cerebral Artery Cerebral Hemorrhage Peptides, Cyclic Oligopeptides Fibrinogen Platelet Glycoprotein GPIIb-IIIa Complex Platelet Aggregation Inhibitors Reperfusion Drug Evaluation, Preclinical Platelet Activation Vascular Patency Dose-Response Relationship, Drug Male |
DOI: | 10.1161/01.STR.31.6.1402 |
Published version: | http://dx.doi.org/10.1161/01.str.31.6.1402 |
Appears in Collections: | Aurora harvest 2 Surgery publications |
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