title: Platelet protective effect of TAK-029, a novel glycoprotein IIb/IIIa antagonist: an in vitro study.
abstract: Previous studies have indicated that exposure of fibrinogen receptors associated with the glycoprotein IIb/IIIa complex contributes to platelet loss during cardiopulmonary bypass. TAK-029 is a newly developed reversible, nonpeptide inhibitor of platelet glycoprotein IIb/IIIa receptors. In this study, we tested the platelet preserving effect of TAK-029 in an in vitro model. The methods included the comparison of the release of beta-thromboglobulin (beta-TG) between a TAK-029 group (n = 5) and a control group (n = 5) in a mock circulation under a shear force generated by a centrifugal pump. To evaluate the degree of beta-TG release, deltabeta-TG/deltaT was calculated where deltabeta-TG is the increase in beta-TG and deltaT is the time. The results showed that the value of deltabeta-TG/deltaT in the TAK-029 group was significantly lower than it was in the control group (4.22 +/- 0.27 x 10(2) ng/ml vs. 7.33 +/- 0.66 x 10(2) ng/ml, respectively). In conclusion, TAK-029 reduced the platelet activation under the shear forces of an in vitro model, suggesting that TAK-029 is a potential candidate for platelet protection during cardiopulmonary bypass.
authors.affiliation: Department of Cardiovascular Surgery, Jichi Medical School, Kawachi, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawahito
authors.forename: A
authors.initials: A
authors.lastname: Fujimura
authors.forename: E
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Misawa
authors.forename: K
authors.initials: K
authors.lastname: Fuse
mesh_terms: D001792:Blood Platelets / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D002498:Centrifugation; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011719:Pyrazines / Q000494:pharmacology*; D013314:Stress, Mechanical; D001620:beta-Thromboglobulin / Q000032:analysis
chemical_list: D005343:Fibrinolytic Agents; D006146:Guanidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011719:Pyrazines; D001620:beta-Thromboglobulin; C099142:TAK 029