PROMOTION OF MYOCARDIAL ANGIOGENESIS USING PEPTIDE GROWTH FACTORS

几种可能导致血管生长的多肽 在过去的几年里， 年 我们的最终目标是利用这些血管生成剂， 促进冠心病患者心肌血运重建 疾病 碱性成纤维细胞生长因子（BFGF）是一种这样的肽， 可能在冠状动脉侧支形成中起重要作用。 我们最近 表明全身给予BFGF可加速冠状动脉粥样硬化， 在犬单冠状动脉闭塞模型中的侧支发展; 然而，对照犬的侧支生长在5周时有所改善， 研究的终点，这样BFGF中侧支流动的增加 在研究结束时基本上消除了治疗的狗。 这个“抓 “上升”现象表明，BFGF将加速 抵押品，但对抵押品的最终大小影响不大 流 进行了一项长期交叉研究，以检查是否：1） bFGF诱导的侧支血流量增加持续超过 5周，2）超过5周的治疗进一步改善侧支血 血流，以及3）停止治疗导致侧支循环消退 血流 狗受到ameroid诱导闭塞的左 随机接受BFGF 1.74 mg/d， 9周，BFGF 1.74 mg/d，持续5周，交叉至安慰剂或生理盐水 9周。 侧支循环血流量用微球评估， 最大冠状血管舒张。 犬的最大侧支血流量 用BFGF治疗9周的狗与治疗5周的狗相似 周，两组的侧支血流明显优于 对照 bFGF治疗犬的主要改善发生在10- 20周期间。 放置ameroid后间隔17天。 因此，bFGF诱导的增加 侧支血流持续超过5周，侧支血流 对照组没有“赶上”治疗犬的水平（差异 9周组间= 25%，p<0.005）。 回归不会发生， 停止治疗。 治疗9周没有优势， 5周治疗，早期治疗显得非常重要。

Several polypeptides with the potential to cause blood vessel growth (angiogenesis) have been sequenced and synthesized during the last few years. Our ultimate goal is to utilize these angiogenic 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 recently demonstrated that systemic administration of BFGF accelerates coronary collateral development in a canine model of single coronary occlusion; however, collateral growth in control dogs improved towards the 5 week end-point of the study, such that the gain in collateral flow in the BFGF treated dogs was essentially erased at the end of the study. This "catch up" phenomenon suggested that BFGF would accelerate the formation of collaterals, but have little effect on the final magnitude of collateral flow. A long-term crossover study was undertaken to examine whether: 1) the BFGF-induced increase in collateral blood flow is sustained beyond 5 weeks, 2) treatment beyond 5 weeks further improves collateral blood flow, and 3) withdrawal of treatment results in regression of collateral blood flow. Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery, and randomized to receive BFGF 1.74 mg/d for 9 weeks, BFGF 1.74 mg/d for 5 weeks, crossing over to placebo, or saline for 9 weeks. Collateral blood flow was assessed with microspheres during maximal coronary vasodilatation. Maximal collateral blood flow in dogs treated with BFGF for 9 weeks was similar to that of dogs treated for 5 weeks, and collateral flow in both groups was significantly better than controls. The major improvement in BFGF-treated dogs occurred during 10- 17 day interval after ameroid placement. Thus, the BFGF-induced increase in collateral flow was sustained beyond 5 weeks, collateral blood flow in controls did not "catch up" to that of treated dogs (difference between groups at 9 weeks = 25%, p<0.005). Regression did not occur when treatment was stopped. Treatment for 9 weeks afforded no advantage over 5 week treatment, and early treatment appeared to be highly important.