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|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|
del Zoppo, G.
|Citation:||Stroke, 2000; 31(6):1402-1410|
|Publisher:||Lippincott Williams & Wilkins|
|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|
|Appears in Collections:||Surgery publications|
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