A synthetic tetrapeptide as a novel platelet-preserving agent during cardiopulmonary bypass.
The possibility of using the synthetic tetrapeptide arginine-glycine-aspartic acid-serine (Arg-Gly-Asp-Ser, RGDS), which was recently identified as the common cell attachment site of adhesive plasma proteins, for platelet preservation during cardiopulmonary bypass (CPB) was investigated. The synthetic RGDS inhibited platelet aggregation and adhesion and secretion of thromboxane A2 in a dose-dependent manner, due to antagonistic inhibition via ligand-receptor interaction. Platelet consumption during CPB was drastically reduced by the administration of RGDS with no remarkable change in hemodynamics and a fairly rapid recovery of platelet functions. Electron microscopic observation revealed that this platelet-preserving effect of RGDS resulted from the inhibition of adhesion and aggregation on the artificial surface. These strongly indicate that the cell attachment site of adhesive plasma proteins plays an important role in platelet consumption during CPB. The synthetic RGDS acting as an antagonist of the platelet membrane receptor, is a novel platelet-preserving agent, especially useful when using an extracorporeal circuit with a large blood-material contact area, such as CPB.
Tatsumi
E
E
Department of Artificial Organs, National Cardiovascular Center, Osaka, Japan.
Matsuda
T
T
Takano
H
H
Taenaka
Y
Y
Noda
H
H
Kinoshita
M
M
Sekii
H
H
Yagura
A
A
Takaichi
S
S
Akutsu
T
T
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen; D008855:Microscopy, Electron, Scanning; D009842:Oligopeptides / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine