PROMOTION OF MYOCARDIAL ANGIOGENESIS VIA DIRECT APPLICATION OF FGF TO HEART

通过直接将 FGF 应用于心脏促进心肌血管生成

• 批准号: 3858121
• 负责人: E UNGER
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3858121
• 关键词: angiogenesis; angiography; collateral circulation; coronary disorder; dogs; fibroblast growth factor; heart circulation; myocardial ischemia /hypoxia; vascular smooth muscle

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.

几种可能导致血管生长的多肽 （血管生成）在过去几年中已被确定。 我们的 最终目标是利用这些药物来促进心肌 冠心病患者的血运重建。 基本的 成纤维细胞生长因子（bFGF）就是这样一种肽，可能发挥 在冠状动脉侧枝形成中起重要作用。 我们研究了效果 bFGF 对逐渐闭塞犬侧支血流的影响 左冠状动脉回旋支（LCX）。 在这个实验中，LCX 在 2 至 3 周内逐渐被 ameroid 缩螽闭塞 应用于近端血管，使其灌注区域依赖 在侧支血管上。 ameroid 放置后 10 天开始，bFGF 110 每日推注微克 (N=8) 或盐水 (N=11) 直接进入位于 ameroid 远端的 LCX 中。 心肌 3天后用放射性标记的微球测定血流量 ameroid 安置，此后 5 周每周一次。 侧支流量为 在染色质诱导的最大血管舒张过程中进行量化，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；最终的 治疗组的 IZ/NZ 血流量比分别为 0.49+/-0.13 和 0.34+/-0.08 和对照组（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中的侧支血流 闭塞。