Integrin α IIb β 3 Inhibitor Preserves Microvascular Patency in Experimental Acute Focal Cerebral Ischemia
| Autor: | C. Mazur, Robert Fitridge, Michael D. Pierschbacher, B. R. Copeland, Takeo Abumiya, G. J. Del Zoppo, Juerg F. Tschopp, James A. Koziol |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Pathology medicine.medical_specialty Drug Evaluation Preclinical Ischemia Platelet Glycoprotein GPIIb-IIIa Complex Peptides Cyclic Basal Ganglia Brain Ischemia Brain ischemia medicine Animals Vascular Patency Platelet activation Cerebral Hemorrhage Microvascular occlusion Advanced and Specialized Nursing Dose-Response Relationship Drug business.industry Microcirculation Fibrinogen Infarction Middle Cerebral Artery Heparin Platelet Activation medicine.disease Anesthesia Reperfusion Platelet aggregation inhibitor Neurology (clinical) Cardiology and Cardiovascular Medicine business Oligopeptides Platelet Aggregation Inhibitors Papio medicine.drug |
| Zdroj: | Stroke. 31:1402-1410 |
| ISSN: | 1524-4628 0039-2499 |
| DOI: | 10.1161/01.str.31.6.1402 |
| Popis: | Background and Purpose —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 α IIb β 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). Methods —TP9201 is a novel Arg-Gly-Asp (RGD)-containing integrin α IIb β 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. Results —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-μm-diameter (capillary) and 7.5- to 30.0-μm-diameter vessels (2 P 2 analysis for trend, P Conclusions —Platelet activation contributes significantly to ischemic microvascular occlusion. Occlusion formation may be prevented by this RGD–integrin α IIb β 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. |
| Databáze: | OpenAIRE |
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