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含有1型成纤维细胞生长因子和肝素的纤维蛋白胶可减少血小板沉积。

Fibrin glue containing fibroblast growth factor type 1 and heparin decreases platelet deposition.

作者信息

Zarge J I, Husak V, Huang P, Greisler H P

机构信息

Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153, USA.

出版信息

Am J Surg. 1997 Aug;174(2):188-92. doi: 10.1016/s0002-9610(97)00090-1.

Abstract

BACKGROUND

The early success rates of endarterectomy and angioplasty are influenced by the thrombogenicity of the deendothelialized surface. We previously reported decreased platelet deposition after 30 and 120 minutes and after 28 days on expanded polytetrafluoroethylene (ePTFE) grafts coated with fibrin glue (FG) containing fibroblast growth factor type 1 (FGF-1) and heparin in canine aortoiliac bypass grafts when compared with control uncoated grafts. The FG/FGF-1/heparin coating has been shown to enhance spontaneous endothelialization at 28 days in canine ePTFE bypass grafts. The current study evaluates the thrombogenicity of this FG/FGF-1/heparin suspension applied to a balloon de-endothelialization model of endarterectomy in canine carotid arteries.

METHODS

Nine dogs underwent bilateral, deendothelialization balloon injury to 6-cm segments of their carotid arteries. Fibrin glue (fibrinogen 32.1 mg/mL + thrombin 0.32 U/mL) containing FGF-1 (11 ng/mL) and heparin (250 U/mL) was applied to the luminal surface of one carotid artery in each dog. Both femoral arteries were circumferentially dissected but not balloon injured; one femoral artery was clamped for the same period as the carotid arteries. In the 6 acute dogs, 10 minutes prior to the restitution of flow in both carotid arteries and one femoral artery, 4 to 8 x 10(9) (111)In-labelled autologous platelets were injected intravenously. Four-cm segments of both carotid and femoral arteries were excised after 15 or 120 minutes of circulation (n = 3/time/artery, 24 arteries). In the 3 chronic dogs, the radiolabelled platelets were injected 30 days after carotid injury. The carotid and femoral vessels were then excised after 120 minutes of perfusion. Radioactive platelet deposition was quantitated by gamma counting.

RESULTS

After 2 hours, the injured carotid arteries demonstrated significantly more platelet deposition than either uninjured femoral artery controls (P < 0.001). There was also a significant 45.2% decrease (P = 0.008) in platelet deposition on the balloon injured carotid arteries treated with FG/FGF-1/heparin when compared with balloon injured carotid arteries alone. At 30 days there was an insignificant trend toward decreased thrombogenicity in the FG/FGF-1/heparin treated injured carotids.

CONCLUSION

Surface coating with FG/FGF-1/heparin significantly decreases platelet deposition on balloon injured canine carotid arteries after 2 hours of perfusion and may be clinically applicable in endarterectomy and angioplasty procedures. The long-term induction of reendothelialization of arterial surfaces by this technique is under investigation.

摘要

背景

动脉内膜切除术和血管成形术的早期成功率受去内皮化表面血栓形成性的影响。我们之前报道,在犬主动脉髂动脉旁路移植术中,与未涂层的对照移植物相比,在涂有含1型成纤维细胞生长因子(FGF-1)和肝素的纤维蛋白胶(FG)的膨体聚四氟乙烯(ePTFE)移植物上,30分钟、120分钟以及28天后血小板沉积减少。FG/FGF-1/肝素涂层已被证明可增强犬ePTFE旁路移植物在28天时的自发内皮化。本研究评估了这种FG/FGF-1/肝素悬浮液应用于犬颈动脉内膜切除术球囊去内皮化模型的血栓形成性。

方法

9只犬双侧颈动脉6厘米节段接受球囊去内皮化损伤。将含FGF-1(11纳克/毫升)和肝素(250单位/毫升)的纤维蛋白胶(纤维蛋白原32.1毫克/毫升+凝血酶0.32单位/毫升)应用于每只犬一侧颈动脉的管腔表面。双侧股动脉均进行环形解剖但未接受球囊损伤;一侧股动脉夹闭时间与颈动脉相同。在6只急性实验犬中,在双侧颈动脉和一侧股动脉恢复血流前10分钟,静脉注射4至8×10⁹个(¹¹¹)铟标记的自体血小板。循环15或120分钟后(每组3只犬/每个时间点/每条动脉,共24条动脉),切除双侧颈动脉和股动脉4厘米节段。在3只慢性实验犬中,在颈动脉损伤30天后注射放射性标记血小板。然后在灌注120分钟后切除颈动脉和股血管。通过γ计数对放射性血小板沉积进行定量。

结果

2小时后,损伤的颈动脉显示出比任何未损伤的股动脉对照更多的血小板沉积(P<0.001)。与仅接受球囊损伤处理的颈动脉相比,接受FG/FGF-1/肝素处理的球囊损伤颈动脉上的血小板沉积也显著减少45.2%(P = 0.008)。在30天时,接受FG/FGF-1/肝素处理的损伤颈动脉的血栓形成性有不显著的下降趋势。

结论

FG/FGF-1/肝素表面涂层在灌注2小时后可显著减少球囊损伤的犬颈动脉上的血小板沉积,可能在临床上适用于动脉内膜切除术和血管成形术。目前正在研究通过该技术长期诱导动脉表面再内皮化的情况。

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