Juerg F. Tschopp

Integrin αIIbβ3 Inhibitor Preserves Microvascular Patency in Experimental Acute Focal Cerebral Ischemia

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 αIIbβ3) 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 αIIbβ3 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: IC80 in heparin, n=4), low-dose TP9201 (group B: IC30 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 w...