Efficacy of FK633, an ultra-short acting glycoprotein IIb/IIIa antagonist on platelet preservation during and after cardiopulmonary bypass.
OBJECTIVE
Temporary pharmacologic inhibition of platelet function during and after cardiopulmonary bypass (CPB) (platelet anesthesia) is an attractive strategy for preserving platelets during CPB. We examined the efficacy of FK633, an ultra-short acting glycoprotein IIb/IIIa antagonist.


METHODS
The study was carried out in six mongrel dogs that received an intravenous bolus of 0.1 mg/kg of FK633 at the time of administration of heparin (group F), and six control dogs (group C). All animals underwent 60 min of normothermic CPB followed by a 2-h observation period. Blood samples for platelet count, platelet aggregation to adenosine diphosphate and parameters concerning the coagulation system were obtained at eight time points. Hemodynamics, bleeding time, and postoperative blood loss were assessed serially. Scanning electron micrograph of the oxygenator's membrane was investigated.


RESULTS
FK633 significantly protected platelet number (group F, 59+/-10% versus group C, 38+/-15% of the pre-CPB value; P < 0.01), and inhibited platelet aggregation to adenosine diphosphate (group F, 13+/-12% versus group C, 35+/-9% of the pre-CPB value; P < 0.01) during CPB. Postoperative blood loss did not significantly differ between the two groups, but there was a tendency of less bleeding in group F (group F, 73+/-23 ml versus group C, 111+/-44 ml; P = 0.09). In group F, scanning electron micrograph of the oxygenator's membrane showed that its surface was free from platelets. There were no significant differences between the groups in hemodynamics.


CONCLUSIONS
An ultra-short acting glycoprotein IIb/IIIa antagonist, FK633, is effective in preventing both platelet aggregation and thrombocytopenia during CPB, and may be effective for minimizing postoperative bleeding.
Tabata
Shigeki
S
Department of General and Cardiothoracic Surgery, Kanazawa University School of Medicine, Takaramachi 13-1, Kanazawa 920-8641, Japan. 02117tabata@kouseiren-ta.or.jp
Yamaguchi
Syohjiro
S
Nagamine
Hiroshi
H
Tomita
Shigeyuki
S
Arai
Sadahiko
S
Takemura
Hirofumi
H
Watanabe
Go
G
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D004151:Dipeptides / Q000494:pharmacology*; D004285:Dogs; D008855:Microscopy, Electron, Scanning; D010106:Oxygenators; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D019106:Postoperative Hemorrhage / Q000503:physiopathology; D013921:Thrombocytopenia / Q000517:prevention & control; D013997:Time Factors
D004151:Dipeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C103087:((4-(4-amidinophenoxy)butanoyl)aspartyl)valine; D000244:Adenosine Diphosphate