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一种用于预防手术粘连的羧甲基纤维素-肝素组合物。

A carboxymethylcellulose-heparin combination for the prevention of surgical adhesions.

作者信息

Docherty James R, McCormick P Aiden

机构信息

Department of Physiology, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

Liver Unit, St. Vincent's University Hospital, Dublin 4, Ireland.

出版信息

J Surg Res. 2017 Jun 1;213:228-233. doi: 10.1016/j.jss.2017.02.066. Epub 2017 Mar 6.

Abstract

BACKGROUND

Adhesions are a major clinical problem after abdominal surgery. Despite decades of research, therapies to prevent adhesion formation are suboptimal.

MATERIALS AND METHODS

We have investigated combinations of carboxymethylcellulose (CMC) and heparin at preventing surgical adhesions in two rat models of adhesion formation. The first was the well-established cecal abrasion model, and the second was a model developed in our laboratory, the avascular mesenteric knot model. This model consistently produced adhesions at the knot in 90% of experiments and causes little or no tissue injury.

RESULTS

Topical administration of CMC 4% gave optimal results in the avascular knot model, but was less effective in the cecal abrasion model. This concentration of CMC was combined with a range of heparin doses between 0.5 and 160 IU/mL in the cecal abrasion model. These heparin doses, apart from the lowest (0.5 IU/mL), were effective in preventing adhesion formation in combination with CMC, as was the commercially available topical product Lipactin. The optimal dose was 30 IU/mL, that abolished adhesions, but there was little difference at doses between 2 and 160 IU. Heparin was effective in doses as low as 2 IU/mL when in combination with CMC. Heparin 160 IU/mL, but not heparin 30 IU/mL or Lipactin, significantly increased the degree of bleeding post cecal abrasion surgery.

CONCLUSIONS

Topical application of tiny doses of heparin, in combination with CMC 4% gel, significantly reduces adhesion formation in experimental models. We suggest that this cheap and, as far as we know, safe intervention should be evaluated in human clinical trials.

摘要

背景

粘连是腹部手术后的一个主要临床问题。尽管经过数十年的研究,但预防粘连形成的治疗方法仍不尽人意。

材料与方法

我们在两种粘连形成的大鼠模型中研究了羧甲基纤维素(CMC)和肝素联合预防手术粘连的效果。第一种是成熟的盲肠擦伤模型,第二种是我们实验室开发的模型——无血管肠系膜结模型。该模型在90%的实验中能在结处持续产生粘连,且几乎不造成组织损伤。

结果

在无血管结模型中,局部应用4%的CMC效果最佳,但在盲肠擦伤模型中效果较差。在盲肠擦伤模型中,将该浓度的CMC与0.5至160 IU/mL的一系列肝素剂量联合使用。除最低剂量(0.5 IU/mL)外,这些肝素剂量与CMC联合使用时均能有效预防粘连形成,市售局部用产品Lipactin也是如此。最佳剂量为30 IU/mL,可消除粘连,但2至160 IU之间的剂量差异不大。肝素与CMC联合使用时,低至2 IU/mL的剂量也有效。160 IU/mL的肝素,但30 IU/mL的肝素或Lipactin则不会,会显著增加盲肠擦伤手术后的出血程度。

结论

局部应用小剂量肝素与4%的CMC凝胶联合使用,可显著减少实验模型中的粘连形成。我们建议应在人类临床试验中评估这种廉价且据我们所知安全的干预措施。

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