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在兔创伤性吻合模型中使用抗凝剂肝素和重组水蛭素的比较研究。

Comparative study on the use of anticoagulants heparin and recombinant hirudin in a rabbit traumatic anastomosis model.

作者信息

Fu K, Izquierdo R, Walenga J M, Fareed J

机构信息

Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA.

出版信息

Thromb Res. 1995 Jun 1;78(5):421-8. doi: 10.1016/0049-3848(95)00075-3.

Abstract

Antithrombotic drugs, such as heparin, have been used in the clinics for a long time. Heparin acts by binding with antithrombin III to form a complex thereby enhancing the activity of antithrombin III to inactivate coagulation factors IIa, IXa, Xa, XIa and XIIa. Hirudin is a new antithrombotic agent and is reported to be much more powerful than heparin on a gravimetric basis. When both are administered systemically, one of the common complications seen is bleeding. Some previous studies have shown that local vascular endothelial concentrations of heparin are 30 to 7500 times greater than those found in the circulating blood. In order to avoid such complications, topical administration of antithrombotic drugs may be an ideal route of administration. The rabbit ear arterial crush-avulsion thrombosis model was used in this study. The animals were divided into five groups: one control group and four treatment groups which received varying concentrations of heparin and hirudin. In the saline control group, the patency rate was 19.23% at 24 hrs and 15.38% at 7 days. A higher patency rate at 7 days was obtained in groups treated with high concentration of heparin and hirudin. ACT, PT and APTT performed on samples drawn one hour after drug administration were within the normal range in both the control and the treatment groups. Scanning electron microscopy revealed the different extent of the clots on the injured intimal surfaces of the vessels in different groups. The results indicate that high concentrations of topically administered heparin or hirudin minimize the systemic complications and maximize the antithrombotic effects.

摘要

抗血栓药物,如肝素,已在临床上使用很长时间。肝素通过与抗凝血酶III结合形成复合物来发挥作用,从而增强抗凝血酶III使凝血因子IIa、IXa、Xa、XIa和XIIa失活的活性。水蛭素是一种新型抗血栓药物,据报道,按重量计算,其效力比肝素强得多。当两者全身给药时,常见的并发症之一是出血。一些先前的研究表明,局部血管内皮中的肝素浓度比循环血液中的浓度高30至7500倍。为了避免此类并发症,局部应用抗血栓药物可能是一种理想的给药途径。本研究使用兔耳动脉挤压 - 撕脱血栓形成模型。将动物分为五组:一组对照组和四组治疗组,治疗组接受不同浓度的肝素和水蛭素。在生理盐水对照组中,24小时时通畅率为19.23%,7天时为15.38%。高浓度肝素和水蛭素治疗组在7天时获得了更高的通畅率。给药一小时后采集的样本进行的活化凝血时间(ACT)、凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)在对照组和治疗组中均在正常范围内。扫描电子显微镜显示不同组血管内膜损伤表面血栓形成的程度不同。结果表明,局部应用高浓度的肝素或水蛭素可将全身并发症降至最低,并使抗血栓作用最大化。

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