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多孔灌注球囊递送血管肽对兔球囊损伤后肌内膜增生的影响。

The effect of porous infusion balloon-delivered angiopeptin on myointimal hyperplasia after balloon injury in the rabbit.

作者信息

Hong M K, Bhatti T, Matthews B J, Stark K S, Cathapermal S S, Foegh M L, Ramwell P W, Kent K M

机构信息

Department of Cardiology, Washington Hospital Center, Washington, DC 20010-2975.

出版信息

Circulation. 1993 Aug;88(2):638-48. doi: 10.1161/01.cir.88.2.638.

Abstract

BACKGROUND

Angiopeptin, a synthetic somatostatin analogue, reduces myointimal hyperplasia after experimental balloon angioplasty when given subcutaneously. The feasibility and efficacy of a single dose of angiopeptin delivered locally via the Wolinsky porous balloon on myointimal hyperplasia were studied.

METHODS AND RESULTS

Three rabbits received 125I-angiopeptin in the mid abdominal aorta via the Wolinsky balloon at 5 atm for 1 minute after balloon injury. Thirty minutes later, autoradiography demonstrated radioactivity in the media and the adventitia. Forty rabbits were divided equally into one control group receiving saline and three angiopeptin groups receiving 1, 10, or 100 micrograms/mL of angiopeptin delivered locally at 5 atm for 1 minute via the Wolinsky balloon into the mid abdominal aorta after balloon injury of the entire abdominal aorta. On day 21, the abdominal aortas were fixed in situ and harvested. There was no statistical difference in the amount of myointimal hyperplasia in the locally treated aorta in the angiopeptin groups compared with the control group. However, in the lower abdominal aorta, where balloon injury without local delivery was performed, there was a significant reduction of myointimal hyperplasia in the highest-concentration angiopeptin group (P < .001 versus the control group). Electron microscopy showed that the control animals had a pseudointima of smooth muscle cells throughout the aorta, whereas in all the angiopeptin-treated animals, endothelial cells were present at both locations.

CONCLUSIONS

Angiopeptin can be delivered intramurally via the Wolinsky porous balloon and reduces myointimal hyperplasia only in the area distal to the local drug delivery site (downstream effect), possibly by healing the injured endothelium, by transport via the vasa vasora, and/or by systemic effect.

摘要

背景

血管肽素,一种合成的生长抑素类似物,皮下给药时可减少实验性球囊血管成形术后的肌内膜增生。本研究探讨了通过沃林斯基多孔球囊局部给予单剂量血管肽素对肌内膜增生的可行性和疗效。

方法与结果

三只兔子在球囊损伤后,通过沃林斯基球囊在5个大气压下于腹主动脉中段注入125I-血管肽素1分钟。30分钟后,放射自显影显示中膜和外膜有放射性。40只兔子被平均分为一个接受生理盐水的对照组和三个血管肽素组,在整个腹主动脉球囊损伤后,通过沃林斯基球囊在5个大气压下于腹主动脉中段局部给予1、10或100微克/毫升的血管肽素1分钟。在第21天,将腹主动脉原位固定并取出。与对照组相比,血管肽素组局部治疗的主动脉中肌内膜增生量无统计学差异。然而,在未进行局部给药的球囊损伤的腹主动脉下段,最高浓度血管肽素组的肌内膜增生明显减少(与对照组相比,P <.001)。电子显微镜显示,对照动物的整个主动脉有平滑肌细胞构成的假内膜,而在所有接受血管肽素治疗的动物中,两个部位均有内皮细胞。

结论

血管肽素可通过沃林斯基多孔球囊壁内给药,且仅在局部药物递送部位远端区域(下游效应)减少肌内膜增生,可能是通过修复受损内皮、通过血管滋养管运输和/或通过全身效应实现的。

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