Platelet preservation with a glycoprotein IIb/IIIa inhibitor in a porcine cardiopulmonary bypass model.
BACKGROUND
We tested whether administration of FK633, a short-acting glycoprotein IIb/IIIa inhibitor, before median sternotomy and cardiopulmonary bypass was able to interrupt the platelet activation loop and thereby preserve platelet number and function.


METHODS
This study investigated 16 pigs that underwent median sternotomy and 120 minutes of normothermic cardiopulmonary bypass (100 mL/kg) adding pericardial blood to the perfusate. FK633 was administered with heparin to one group (group F, n = 8), whereas only heparin was administered to the control group (group C, n = 8). Blood samples were obtained at several times, and complete blood count, platelet aggregation to adenosine diphosphate, thrombin-antithrombin complex, and bradykinin were evaluated. P-selectin expression and fibrinogen binding on platelet surfaces were measured by flow cytometry. Template bleeding times were measured before and after cardiopulmonary bypass. Chest tube drainage and hematocrit were determined at 2 and 6 hours after cardiopulmonary bypass.


RESULTS
In group F, platelet counts were preserved from 90 minutes of cardiopulmonary bypass. Platelet aggregation was inhibited at the beginning of cardiopulmonary bypass and showed no change at wound closure, and bleeding times were shortened at 2 hours after cardiopulmonary bypass. There were significant reductions in hematocrit of drainage. Flow cytometry showed no changes in P-selectin expression and fibrinogen binding in group F, whereas P-selectin expression and fibrinogen binding were elevated in group C.


CONCLUSIONS
Platelet inhibition with FK633 before invasive surgical procedure preserved platelet counts during and after cardiopulmonary bypass, and produced normal or near-normal bleeding times in the immediate postoperative period.
First Department of Surgery, Hirosaki University School of Medicine, Aomori, Japan. h02gm501@cc.hirosaki-u.ac.jp
Norihiro
N
Kondo
Yasuyuki
Y
Suzuki
Fuminori
F
Wakayama
Yoshiko
Y
Tamai
Kaiqiang
K
Ji
Kozo
K
Fukui
Ikuo
I
Fukuda
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013552:Swine
D004151:Dipeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C103087:((4-(4-amidinophenoxy)butanoyl)aspartyl)valine