Kondo Norihiro, Suzuki Yasuyuki, Wakayama Fuminori, Tamai Yoshiko, Ji Kaiqiang, Fukui Kozo, Fukuda Ikuo
First Department of Surgery, Hirosaki University School of Medicine, Aomori, Japan.
Ann Thorac Surg. 2005 Jul;80(1):251-7. doi: 10.1016/j.athoracsur.2005.02.020.
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.
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.
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.
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.
我们测试了在正中胸骨切开术和体外循环前给予短效糖蛋白IIb/IIIa抑制剂FK633是否能够中断血小板激活循环,从而维持血小板数量和功能。
本研究调查了16头接受正中胸骨切开术和120分钟常温体外循环(100 mL/kg)并向灌注液中添加心包血的猪。一组(F组,n = 8)在给予肝素的同时给予FK633,而对照组(C组,n = 8)仅给予肝素。在多个时间点采集血样,并评估全血细胞计数、血小板对二磷酸腺苷的聚集、凝血酶-抗凝血酶复合物和缓激肽。通过流式细胞术测量血小板表面的P-选择素表达和纤维蛋白原结合。在体外循环前后测量模板出血时间。在体外循环后2小时和6小时测定胸管引流量和血细胞比容。
在F组中,从体外循环90分钟起血小板计数得以维持。在体外循环开始时血小板聚集受到抑制,在伤口闭合时无变化,并且在体外循环后2小时出血时间缩短。引流液的血细胞比容显著降低。流式细胞术显示F组中P-选择素表达和纤维蛋白原结合无变化,而C组中P-选择素表达和纤维蛋白原结合升高。
在侵入性手术前用FK633抑制血小板可在体外循环期间和之后维持血小板计数,并在术后即刻产生正常或接近正常的出血时间。