PROMOTION OF MYOCARDIAL ANGIOGENESIS USING PEPTIDE GROWTH FACTORS

几种可能导致血管生长的多肽 (血管生成)在过去的几年中已经被测序和合成 好几年了。我们的最终目标是利用这些血管生成剂(S)来 促进冠心病患者的心肌血运重建 疾病。碱性成纤维细胞生长因子是一种强有力的血管生成因子 可能在冠脉侧支形成中起重要作用的多肽。 我们先前发现冠状动脉内给予碱性成纤维细胞生长因子增加 犬心肌梗死模型体内侧支循环血流量的变化 缺血症。在本研究中，我们研究了全身性碱性成纤维细胞生长因子对脑血流量的影响。 在同一模型中，并评估其潜在的副作用。渐进式 20只犬经皮冠状动脉腔内置管引流术诱发冠状动脉狭窄 船上有一条无毒的毒蛇。从第10天开始，狗收到 每日左侧注射碱性成纤维细胞生长因子(1.74 mg)或生理盐水(n=10) 中庭。治疗28天。微球血流量 在最大血管扩张期间每周确定一次，从第一天开始 3.脑血流量以缺血区/正常区(IZ/NZ)比值表示。不是 不良的全身性影响是显而易见的。在…的第一周 治疗后，碱性成纤维细胞生长因子的IZ/NZ比值从0.06提高到0.34 而对照组从0.12提高到0.16(p=0.015，碱性成纤维细胞生长因子vs. 控制)。在第二周，IZ/NZ比率从0.34增加到 碱性成纤维细胞生长因子处理组为0.42，对照组为0.16至0.19(p&lt；0.001， 碱性成纤维细胞生长因子与对照组)。然而，不同群体之间的差距缩小了 在治疗的第三周和第四周。加速器的加速 抵押品的形成类似于之前观察到的 冠状动脉内给药。期间观察到的“追赶”现象 第3周和第4周表明，碱性成纤维细胞生长因子的反应有一个上限， 更有可能的是，观察到的脑血流量增加消除了这一区域的缺血 犬单支冠状动脉闭塞模型，从而去除所有 进一步刺激抵押品发展。

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 a potent angiogenic peptide that may play an important role in coronary collateral formation. We previously found that intracoronary administration of bFGF increases collateral blood flow (CBF) in vivo, in a canine model of myocardial ischemia. In this study, we examined the effect of systemic bFGF on CBF in the same model, and assessed its potential side effects. Progressive constriction of the LCX coronary artery was induced of 20 dogs by placing ameroid constrictors on the vessel. Beginning on day 10, dogs received daily injection of bFGF (1.74 mg, n=10) or saline (n=10) into the left atrium. Treatment was maintained for 28 days. Microsphere blood flow was determined during maximal vasodilation on a weekly basis, beginning on day 3. CBF was expressed as an ischemic/normal zone (IZ/NZ) ratio. No adverse systemic effects were apparent. During the first week of treatment, the IZ/NZ ratio improved from 0.06 to 0.34 in bFGF treated dogs, while improving from 0.12 to 0.16 in controls (p=0.015, bFGF vs. control). During the second week, the IZ/NZ ratio increased from 0.34 to 0.42 in bFGF treated dogs, and from 0.16 to 0.19 in controls (p<0.001, bFGF vs. control). The disparity between groups, however, diminished during the third and fourth weeks of treatment. The acceleration of collateral formation was similar to that observed previously with intracoronary administration. The "catch up" phenomenon observed during weeks 3 and 4 suggests that there is a ceiling for the bFGF response, or, more likely, the observed increase in CBF abolishes ischemia in this canine model of single vessel coronary occlusion, thereby removing any further stimulus to collateral development.