[Neoangiogenesis by local gene therapy: a new therapeutic concept in the treatment of coronary disease].
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 quantitatively 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.
Schumacher
B
B
Universitätsklinik Ulm, Abt. Chirurgie IV Herzchirurgie.
Hannekum
A
A
Pecher
P
P
D015901:Angiography, Digital Subtraction; D000818:Animals; D001026:Coronary Artery Bypass; D003326:Coronary Circulation; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000601:surgery / Q000628:therapy*; D003331:Coronary Vessels; D004311:Double-Blind Method; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D005500:Follow-Up Studies; D015316:Genetic Therapy; D006133:Growth Substances / Q000008:administration & dosage; D006358:Hot Temperature; D006801:Humans; D008323:Mammary Arteries; D018919:Neovascularization, Physiologic; D011489:Protein Denaturation; D011817:Rabbits; D051381:Rats; D013997:Time Factors
D006133:Growth Substances; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1