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https://hdl.handle.net/2440/10459
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dc.contributor.author | Abumiya, T. | - |
dc.contributor.author | Fitridge, R. | - |
dc.contributor.author | Mazur, C. | - |
dc.contributor.author | Copeland, B. | - |
dc.contributor.author | Koziol, J. | - |
dc.contributor.author | Tschopp, J. | - |
dc.contributor.author | Pierschbacher, M. | - |
dc.contributor.author | del Zoppo, G. | - |
dc.date.issued | 2000 | - |
dc.identifier.citation | Stroke, 2000; 31(6):1402-1410 | - |
dc.identifier.issn | 0039-2499 | - |
dc.identifier.issn | 1524-4628 | - |
dc.identifier.uri | http://hdl.handle.net/2440/10459 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | 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 | - |
dc.language.iso | en | - |
dc.publisher | Lippincott Williams & Wilkins | - |
dc.source.uri | http://dx.doi.org/10.1161/01.str.31.6.1402 | - |
dc.subject | Microcirculation | - |
dc.subject | Basal Ganglia | - |
dc.subject | Animals | - |
dc.subject | Papio | - |
dc.subject | Brain Ischemia | - |
dc.subject | Infarction, Middle Cerebral Artery | - |
dc.subject | Cerebral Hemorrhage | - |
dc.subject | Peptides, Cyclic | - |
dc.subject | Oligopeptides | - |
dc.subject | Fibrinogen | - |
dc.subject | Platelet Glycoprotein GPIIb-IIIa Complex | - |
dc.subject | Platelet Aggregation Inhibitors | - |
dc.subject | Reperfusion | - |
dc.subject | Drug Evaluation, Preclinical | - |
dc.subject | Platelet Activation | - |
dc.subject | Vascular Patency | - |
dc.subject | Dose-Response Relationship, Drug | - |
dc.subject | Male | - |
dc.title | Integrin αIIbβ3 inhibitor preserves microvascular patency in experimental acute focal cerebral ischemia | - |
dc.title.alternative | Integrin alphaIIb beta3 inhibitor preserves microvascular patency in experimental acute focal cerebral ischemia | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1161/01.STR.31.6.1402 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Fitridge, R. [0000-0001-6258-5997] | - |
Appears in Collections: | Aurora harvest 2 Surgery publications |
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