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超短效糖蛋白IIb/IIIa拮抗剂FK633在体外循环期间及之后对血小板保存的疗效。

Efficacy of FK633, an ultra-short acting glycoprotein IIb/IIIa antagonist on platelet preservation during and after cardiopulmonary bypass.

作者信息

Tabata Shigeki, Yamaguchi Syohjiro, Nagamine Hiroshi, Tomita Shigeyuki, Arai Sadahiko, Takemura Hirofumi, Watanabe Go

机构信息

Department of General and Cardiothoracic Surgery, Kanazawa University School of Medicine, Takaramachi 13-1, Kanazawa 920-8641, Japan.

出版信息

Eur J Cardiothorac Surg. 2004 Aug;26(2):289-93. doi: 10.1016/j.ejcts.2004.03.036.

Abstract

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.

摘要

目的

在体外循环(CPB)期间及之后对血小板功能进行临时药理学抑制(血小板麻醉)是在CPB期间保存血小板的一种有吸引力的策略。我们研究了超短效糖蛋白IIb/IIIa拮抗剂FK633的疗效。

方法

该研究在6只杂种犬中进行,这些犬在给予肝素时静脉推注0.1mg/kg的FK633(F组),以及6只对照犬(C组)。所有动物均接受60分钟的常温CPB,随后进行2小时的观察期。在八个时间点采集用于血小板计数、血小板对二磷酸腺苷的聚集以及有关凝血系统参数的血样。连续评估血流动力学、出血时间和术后失血量。对氧合器膜进行扫描电子显微镜检查。

结果

FK633在CPB期间显著保护血小板数量(F组为CPB前值的59±10%,而C组为38±15%;P<0.01),并抑制血小板对二磷酸腺苷的聚集(F组为CPB前值的13±12%,而C组为35±9%;P<0.01)。两组术后失血量无显著差异,但F组有出血较少的趋势(F组为73±23ml,而C组为111±44ml;P=0.09)。在F组中,氧合器膜的扫描电子显微镜检查显示其表面无血小板。两组在血流动力学方面无显著差异。

结论

超短效糖蛋白IIb/IIIa拮抗剂FK633在CPB期间有效预防血小板聚集和血小板减少,并且可能对减少术后出血有效。

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