Schumacher B, Hannekum A, Pecher P
Universität Ulm, Abt. Chirurgie IV, Herzchirurgie, Steinhövelstr. 9, D-89075 Ulm, Germany.
Z Kardiol. 2000 Oct;89(Suppl 7):23-30. doi: 10.1007/PL00022882.
This article presents the results of our initial clinical experience with the human growth factor FGF-1 as applied to the ischemic human myocardium.After the completion of extensive preliminary animal experiments, the human angiogenetic growth factor FGF-1, obtained from a genetically transformed strain of E. coli was introduced into aortocoronary bypass surgery as an additional therapeutic agent. A double-blind study was carried out in a total of 40 patients with coronary heart disease. The patients were randomized into growth-factor and control groups, each containing 20 patients. All patients underwent aortocoronary bypass surgery because of their coronary multivessel disease, in each case with an IMA bypass for the LAD and single venous bypasses for the RCX and/or RCA. In order to bridge over additional stenosis of the LAD or one of its branches, the human growth factor FGF-1 was injected into the myocardium during the operation. In the control group heat-denatured growth factor was substituted for FGF-1. After three months as well as three years postoperatively, the IMA bypasses were selectively depicted by intraarterial DSA. These angiographies were then guantitatively evaluated. After the application of the growth factor, the formation of new vessels could be demonstrated after three months as well as three years postoperatively. A capillary network initiating from the coronary artery could be found and the computer-supported evaluation of the angiographs revealed a significant increase in the blood supply of the region of the myocardium injected. According to the angiographic findings there was also a clinical improvement of the patients with FGF-1 application compared to the patients of control group, concerning the NYHA classification as well as the need for antiangina drug therapy.In the meantime, the results of other research groups support the evidence that the induction of neoangiogenesis by human growth factor could become a therapeutic approach especially in patients with diffuse coronary artery disease. Nevertheless further studies have to be carried out in order to prove the long-term clinical profit of those patients after the growth factor treatment.
本文介绍了我们将人类生长因子FGF-1应用于缺血性人类心肌的初步临床经验结果。在完成广泛的初步动物实验后，将从基因改造的大肠杆菌菌株中获得的人类血管生成生长因子FGF-1作为一种额外的治疗剂引入主动脉冠状动脉搭桥手术。对总共40例冠心病患者进行了一项双盲研究。患者被随机分为生长因子组和对照组，每组20例。所有患者均因冠状动脉多支病变接受主动脉冠状动脉搭桥手术，每种情况均采用左前降支的内乳动脉搭桥和回旋支及/或右冠状动脉的单静脉搭桥。为了跨越左前降支或其分支的额外狭窄，术中将人类生长因子FGF-1注入心肌。在对照组中，用热变性生长因子替代FGF-1。术后三个月和三年，通过动脉内数字减影血管造影术（DSA）选择性地描绘内乳动脉搭桥情况。然后对这些血管造影进行定量评估。应用生长因子后，术后三个月和三年均显示有新血管形成。可以发现从冠状动脉起始的毛细血管网络，并且对血管造影照片的计算机辅助评估显示，注入心肌区域的血液供应显著增加。根据血管造影结果，与对照组患者相比，应用FGF-1的患者在纽约心脏协会（NYHA）分级以及抗心绞痛药物治疗需求方面也有临床改善。与此同时，其他研究小组的结果支持了这样的证据，即人类生长因子诱导新生血管生成可能成为一种治疗方法，特别是对于弥漫性冠状动脉疾病患者。然而，为了证明生长因子治疗后这些患者的长期临床获益，还必须进行进一步的研究。
