PROMOTION OF MYOCARDIAL ANGIOGENESIS VIA DIRECT APPLICATION OF FGF TO HEART

几种可能导致血管生长的多肽 （血管生成）在过去几年中已经被鉴定。 我们 最终目标是利用这些药物促进心肌细胞的 冠心病患者的血运重建。 基本 成纤维细胞生长因子（bFGF）就是这样一种肽， 在冠状动脉侧支形成中的重要作用。 我们研究了 bFGF对逐渐闭塞犬侧支循环血流的影响 左回旋支冠状动脉（LCX）。 在这个实验中，LCX是 在2到3周的时间内逐渐被一个Ameroid缩窄器堵塞 应用于近端血管，使其灌注区域依赖于 在侧支血管上 从ameroid放置后10天开始，bFGF 110 微克（N=8）或盐水（N= 11）作为每日推注给予 直接进入左回旋支在一个点的远端ameroid。 心肌 3天后用放射性标记的微球测定血流量 ameroid放置，此后每周一次，持续5周。 侧支循环是 在色原醛诱导的最大血管舒张期间定量，并表示为 缺血区/正常区（IZ/NZ）比率。 治疗2周后， bFGF治疗犬的IZ/NZ比值超过对照犬;最终 治疗组IZ/NZ血流比为0.49+/-0.13和0.34+/-0.08 与对照组比较，差异有显著性（P<0.05）。我们的结论是冠状动脉内 bFGF增强犬单冠状动脉模型的侧支血流 闭塞

Several polypeptides with the potential to cause blood vessel growth (angiogenesis) have been identified during the last few years. Our ultimate goal is to utilize these agent(s) to facilitate myocardial revascularization in patients with coronary heart disease. Basic fibroblast growth factor (bFGF) is one such peptide that may play an important role in coronary collateral formation. We studied the effect of bFGF on collateral blood flow in dogs subjected to gradual occlusion of the left circumflex coronary artery (LCX). In this experiment, the LCX was occluded gradually over a 2 to 3 week period by an ameroid constrictor applied to the proximal vessel, rendering its perfusion territory dependent on collateral vessels. Beginning 10 days after ameroid placement, bFGF 110 micrograms (N=8) or saline (N=ll) was given as a daily bolus injection directly into the LCX at a point just distal to the ameroid. Myocardial blood flow was determined with radiolabeled microspheres 3 days after ameroid placement and weekly for 5 weeks thereafter. Collateral flow was quantified during chromonar-induced maximal vasodilation and expressed as an ischemic/normal zone (IZ/NZ) ratio. After 2 weeks of treatment, the IZ/NZ ratio in bFGF treated dogs surpassed that of control dogs; final IZ/NZ blood flow ratios were 0.49+/-0.13 and 0.34+/-0.08 in the treated and control groups, respectively (p<0.05). We conclude that intracoronary bFGF enhances collateral blood flow in this canine model of single coronary occlusion.