Pharmacologic platelet anesthesia by glycoprotein IIb/IIIa complex antagonist and argatroban during in vitro extracorporeal circulation.
OBJECTIVE
Contact between blood and the synthetic surfaces of a cardiopulmonary bypass circuit leads to platelet activation, and resultant platelet dysfunction contributes to postoperative bleeding. We compared the effects of various platelet inhibitors on preservation of platelet function during simulated cardiopulmonary bypass circulation.


METHODS
Fresh human blood was recirculated in an in vitro cardiopulmonary bypass model circuit. We measured various platelet activation markers including expressions of PAC-1 and P-selectin, annexin V binding, and microparticle formations by means of whole-blood flow cytometry.


RESULTS
Two types of glycoprotein IIb/IIIa complex antagonists, peptide-mimetic FK633 and abciximab and prostaglandin E(1), significantly prevented platelet loss and the increase in binding of PAC-1, an antibody specific for fibrinogen receptor on activated platelets, during extracorporeal circulation of heparinized blood. These antagonists significantly suppressed but did not abolish P-selectin expression, annexin V binding, and microparticle formation. Anti-von Willebrand factor monoclonal antibody and aurin tricarboxylic acid (an inhibitor of glycoprotein Ib) had no effect on platelet activation during simulated cardiopulmonary bypass circulation. These data suggest that inhibition of fibrinogen binding glycoprotein IIb/IIIa complex is partly effective in attenuating platelet activation in a heparinized cardiopulmonary bypass model circuit. The direct thrombin inhibitor argatroban prevented platelet loss and expression of P-selectin significantly more than did heparin. A combination of FK633 with argatroban as a substitute for heparin further prevented platelet loss and platelet secretion during simulated cardiopulmonary bypass circulation, although the inhibition of microparticle formation was less.


CONCLUSIONS
The inhibition of both platelet adhesion and thrombin may be effective to preserve platelet number and function during cardiopulmonary bypass circulation.
Kanemitsu
Shinji
S
Department of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Nishikawa
Masakatsu
M
Onoda
Koji
K
Shimono
Takatsugu
T
Shimpo
Hideto
H
Yazaki
Akira
A
Tanaka
Kuniyoshi
K
Shiku
Hiroshi
H
Yada
Isao
I
D000077284:Abciximab; D000527:Alprostadil / Q000097:blood / Q000494:pharmacology; D000758:Anesthesia; D017304:Annexin A5 / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D004151:Dipeptides / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D054641:Dual Specificity Phosphatase 2; D005112:Extracorporeal Circulation; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000494:pharmacology; D019007:P-Selectin / Q000187:drug effects; D010875:Pipecolic Acids / Q000097:blood / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000494:pharmacology*; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000187:drug effects; D040201:Platelet Membrane Glycoprotein IIb / Q000187:drug effects; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000187:drug effects; D013449:Sulfonamides; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000187:drug effects
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D004151:Dipeptides; D004338:Drug Combinations; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D040201:Platelet Membrane Glycoprotein IIb; D013449:Sulfonamides; D014841:von Willebrand Factor; C103087:((4-(4-amidinophenoxy)butanoyl)aspartyl)valine; D006493:Heparin; D001120:Arginine; D054648:Protein Phosphatase 2; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2; D017027:Protein Tyrosine Phosphatases; D000527:Alprostadil; C031942:argatroban; D000077284:Abciximab