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直接口服抗凝剂对大鼠动脉挤压伤后显微外科吻合通畅率的抗血栓形成疗效。

Antithrombotic efficacy of direct oral anticoagulants on patency rate following microsurgical anastomosis in crushed rat arteries.

作者信息

Papadopoulos Dimitrios, Gkiatas Ioannis, Batistatou Anna, Papoudou-Bai Alexandra, Kostas Ioannis, Tsantes Andreas G, Korompilias Anastasios V

机构信息

Department of Orthopaedic Surgery, University Hospital of Ioannina, Stavros Niarchos Avenue 1, Ioannina, Greece.

Department of Orthopaedic Surgery, University Hospital of Ioannina, Stavros Niarchos Avenue 1, Ioannina, Greece.

出版信息

J Orthop Sci. 2019 May;24(3):552-557. doi: 10.1016/j.jos.2018.10.011. Epub 2018 Nov 2.

Abstract

BACKGROUND

During the last decade direct oral anticoagulants (DOAC) have been established in various fields of medicine.Their use in microsurgery has not been evaluated yet though. This study aims to evaluate their efficacy in microsurgery and additionally compare them with a well established antithrombotic agent.

MATERIALS AND METHODS

The right femoral artery of 101 rats divided into 4 groups, was crushed and anastomosed. Group A (20 rats) received placebo therapy (1 ml NaCl 0.9%, orally), while Group B (27 rats), Group C (27 rats) and Group D (27 rats) received rivaroxaban (3 mg/kg, orally), dabigatran (30 mg/kg, orally) and enoxaparin (30 mg/kg, subcutaneously) respectively. All drugs were administered 3 h preoperatively and once daily for the following postoperative days until the sacrifice of the animals. Patency was evaluated at 1st, 7th and 20th postoperative day. Following patency evaluation the rats were sacrificed and the vessels were harvested for histological examination.

RESULTS

None of the rats died postoperatively. Patency rates of rivaroxaban group (78%), dabigatran group (70%) and enoxaparin group (63%) were statistically similar, but significantly higher than the placebo-treated control group (p < 0.05). Cells with morphologic features of endothelial cells were evident 7 days after the injury.

CONCLUSION

The results of this study demonstrate the following: (1) rivaroxaban and dabigatran through inhibition of thrombus formation significantly enhanced the patency rate compared to placebo treatment (2) the antithrombotic efficacy of rivaroxaban and dabigatran in compromised microvessels was similar to that of enoxaparin, the most widely used antithrombotic agent.

摘要

背景

在过去十年中,直接口服抗凝剂(DOAC)已在医学各个领域得到应用。不过,其在显微外科手术中的应用尚未得到评估。本研究旨在评估其在显微外科手术中的疗效,并将其与一种成熟的抗血栓药物进行比较。

材料与方法

将101只大鼠分为4组,对其右股动脉进行挤压并吻合。A组(20只大鼠)接受安慰剂治疗(口服1毫升0.9%氯化钠溶液),而B组(27只大鼠)、C组(27只大鼠)和D组(27只大鼠)分别接受利伐沙班(口服3毫克/千克)、达比加群(口服30毫克/千克)和依诺肝素(皮下注射30毫克/千克)治疗。所有药物均在术前3小时给药,术后每天给药一次,直至动物处死。在术后第1天、第7天和第20天评估血管通畅情况。在血管通畅情况评估后,处死大鼠并采集血管进行组织学检查。

结果

术后无大鼠死亡。利伐沙班组(78%)、达比加群组(70%)和依诺肝素组(63%)的血管通畅率在统计学上相似,但显著高于安慰剂治疗的对照组(p<0.05)。损伤后7天可见具有内皮细胞形态特征的细胞。

结论

本研究结果表明:(1)与安慰剂治疗相比,利伐沙班和达比加群通过抑制血栓形成显著提高了血管通畅率;(2)利伐沙班和达比加群在受损微血管中的抗血栓疗效与最广泛使用的抗血栓药物依诺肝素相似。

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