Induction of neoangiogenesis in ischemic myocardium by human growth factors - First clinical results of a new treatment of coronary heart disease

Induction of neoangiogenesis in ischemic myocardium by human growth factors - First clinical results of a new treatment of coronary heart disease
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DOI:
10.1161/01.cir.97.7.645
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发表时间:
1998-02-24
期刊:
影响因子:
37.8
通讯作者:
Stegmann, T
Stegmann, T
中科院分区:
医学1区
文献类型:
--
作者:
Schumacher, B;Pecher, P;Stegmann, T

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背景-本文是我们的动物实验报告,也是使用人生长因子FGF-I(碱性成纤维细胞生长因子)诱导缺血心肌新生血管生成治疗冠心病的新疗法的第一个临床结果。方法和结果-FGF-I是通过基因工程从埃希氏菌菌株中获得,然后分离和高度纯化。几个系列的动物实验证明了该因子的致病作用和新生血管效力。动物实验成功后,首次应用于临床。 20 名三支冠状动脉疾病患者完成乳内动脉 (IMA)/左冠状动脉前降支 (LAD) 吻合后,在血管附近注射 FGF-I(0.01 mg/kg 体重)。所有患者均存在 LAD 或其对角分支之一的额外外周狭窄。十二周后,通过动脉内数字减影血管造影对 IMA 旁路进行选择性成像并进行定量评估。在所有动物实验中,可以通过血管造影证明缺血心肌中新血管的发育。毛细血管的形成也可以在人类身上得到证实,并且在注射部位周围的所有病例中都被发现。从冠状动脉的近端部分萌发的毛细血管网络可以被证明绕过了狭窄并重新连接了血管的远端部分。结论-我们相信使用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无法通过手术进行血运重建的额外外周狭窄的患者。
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 call by genetic engineering, then isolated and highly purified. Several series of animal experiments demonstrated the apathogenic action and neangiogenic 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.