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人生长因子诱导缺血心肌新生血管生成:冠心病新疗法的首个临床结果

Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease.

作者信息

Schumacher B, Pecher P, von Specht B U, Stegmann T

机构信息

Klinik für Thorax-, Herz und Gefässchirurgie, Klinikum Fulda, Germany.

出版信息

Circulation. 1998 Feb 24;97(7):645-50. doi: 10.1161/01.cir.97.7.645.

Abstract

BACKGROUND

The present article is a report of our animal experiments and also of the first clinical results of a new treatment for coronary heart disease using the human growth factor FGF-I (basic fibroblast growth factor) to induce neoangiogenesis in the ischemic myocardium.

METHODS AND RESULTS

FGF-I was obtained from strains of Escherichia coli by genetic engineering, then isolated and highly purified. Several series of animal experiments demonstrated the apathogenic action and neoangiogenic potency of this factor. After successful conclusion of the animal experiments, it was used clinically for the first time. FGF-I (0.01 mg/kg body weight) was injected close to the vessels after the completion of internal mammary artery (IMA)/left anterior descending coronary artery (LAD) anastomosis in 20 patients with three-vessel coronary disease. All the patients had additional peripheral stenoses of the LAD or one of its diagonal branches. Twelve weeks later, the IMA bypasses were selectively imaged by intra-arterial digital subtraction angiography and quantitatively evaluated. In all the animal experiments, the development of new vessels in the ischemic myocardium could be demonstrated angiographically. The formation of capillaries could also be demonstrated in humans and was found in all cases around the site of injection. A capillary network sprouting from the proximal part of the coronary artery could be shown to have bypassed the stenoses and rejoined the distal parts of the vessel.

CONCLUSIONS

We believe that the use of FGF-I for myocardial revascularization is in principle a new concept and that it may be particularly suitable for patients with additional peripheral stenoses that cannot be revascularized surgically.

摘要

背景

本文报告了我们的动物实验以及使用人类生长因子FGF-I(碱性成纤维细胞生长因子)诱导缺血心肌新生血管形成治疗冠心病的首个临床结果。

方法与结果

FGF-I通过基因工程从大肠杆菌菌株中获得,然后进行分离和高度纯化。一系列动物实验证明了该因子的无致病性作用和新生血管生成能力。动物实验成功完成后,首次将其用于临床。对20例三支血管冠心病患者在完成乳内动脉(IMA)/左冠状动脉前降支(LAD)吻合术后,在血管附近注射FGF-I(0.01mg/kg体重)。所有患者的LAD或其对角支之一还存在外周狭窄。12周后,通过动脉内数字减影血管造影对IMA搭桥血管进行选择性成像并进行定量评估。在所有动物实验中,缺血心肌中新生血管的形成均可通过血管造影显示。在人体中也证实了毛细血管的形成,并且在所有注射部位周围均发现了毛细血管。从冠状动脉近端发出的毛细血管网络可以绕过狭窄部位并重新连接到血管的远端。

结论

我们认为,使用FGF-I进行心肌血运重建原则上是一个新概念,并且它可能特别适合于存在无法通过手术进行血运重建的外周狭窄的患者。

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