Reduction in myocardial infarct size by basic fibroblast growth factor following coronary occlusion in a canine model
Reduction in myocardial infarct size by basic fibroblast growth factor following coronary occlusion in a canine model
复制标题
DOI：
10.1016/s0167-5273(98)00296-4
复制
发表时间：
1999-04-10
影响因子：
3.5
通讯作者：
Nicolini, FA
中科院分区：
文献类型：
--
作者：
Horrigan, MCG;Malycky, JL;Nicolini, FA
在永久性冠状动脉闭塞的犬模型中，已经表明碱性成纤维细胞生长因子(BFGF)缩小了梗塞范围，这与梗塞后一周心肌毛细血管密度的增加有关。在我们实验室的一项初步工作中，使用闭塞后延长再灌注的模型，我们观察到在没有心肌新生血管证据的情况下，心肌梗死面积也有类似的缩小，本研究的目的是在一个急性实验中评估bFGF对心肌梗死面积和梗死区血流的影响，在该实验中，心肌新生血管将被排除为一种机制，研究持续时间较短。17只杂种犬麻醉后，通过左胸手术暴露心脏。分离左前降支(LAD)结扎3h，结扎LAD后15min，给予bFGF20mg6只或安慰剂11只，冠脉内注入5min以上。分别于阻断后1、30、180min测量心率、主动脉压、冠脉局部血流量(CBF)、局部心肌短轴缩短率(SF)，再灌流5min后处死动物，测量心肌梗死面积。在整个研究过程中，两组狗之间的局部脑血流量相似。在缺血开始前和缺血期开始时，两组间的SF相似。再灌注期SF为3.4+/-4.6%，安慰剂组为0.4+/-1.0%(P=0.023)。危险区域标准化的梗塞面积，碱性成纤维细胞生长因子组为14.2+/-5.2%，安慰剂组为25.8+/-8.2%(P=0.015)。综上所述，我们已经证明，碱性成纤维细胞生长因子显著限制了急性冠状动脉闭塞后的心肌坏死，而且这种情况没有增加局部心肌灌注，而且在一段太短的时间内不会发生血管生成。通过排除，似乎碱性成纤维细胞生长因子的有益作用可能是由细胞机制介导的。碱性成纤维细胞生长因子挽救心肌的机制可能具有潜在的临床应用价值，可作为急性缺血心肌保护治疗的基础。(C)1999爱思唯尔爱尔兰科学有限公司。保留所有权利。
In a canine model of permanent coronary occlusion it has been shown that basic fibroblast growth factor (bFGF) reduced infarct size and this was associated with an increase in myocardial capillary density a week after infarction. In a preliminary work from our own laboratory using a model of occlusion followed by prolonged reperfusion we observed a similar reduction in infarct size without evidence of myocardial neovascularization, The aim of the present investigation was to evaluate the effects of bFGF on infarct size and blood flow to the infarct zone in an acute experiment in which myocardial neovascularization would be excluded as a mechanism by the short duration of the study. Seventeen mongrel dogs were anesthetized and the heart was exposed through a left thoratocomy. The left anterior descending (LAD) coronary artery was isolated and occluded for 3 h. Fifteen min after LAD occlusion dogs received bFGF 20 mu g of bFGF (n=6) or placebo (n=11) by intracoronary injection infused over 5 min. We measured heart rate, aortic pressure, regional coronary blood flow (CBF), regional shortening fraction (SF) at 1, 30 and 180 min of occlusion, then the LAD was reperfused for 5 min then the dogs were euthanized and infarct size was measured. Regional CBF was similar between the two groups of dogs throughout all the study. The SF was similar between the two groups prior the onset of ischemia and at the beginning of the ischemic period. After 180 min of ischemia SF was 2.7+/-4.1% for bFGF and -3.1+/-4.7 for placebo (P=0.049), and during reperfusion SF was 3.4+/-4.6% for bFGF and 0.4+/-1.0% for placebo treated dogs (P=0.023). The infarct size, normalized for the area at risk was 14.2+/-5.2% in bFGF group vs 25.8+/-8.2% in placebo group (P=0.015). In summary we have demonstrated that bFGF significantly limits myocardial necrosis after acute coronary occlusion, and that this occurred without an increase in regional myocardial perfusion and within a period of time too brief for angiogenesis to have occurred. By exclusion, it appears that the salutary effect of bFGF is likely to be mediated by a cellular mechanism. The mechanism or mechanisms responsible for myocardial salvage by bFGF may have significant potential to be exploited in the clinical arena as the basis for therapies to protect the acutely ischemic myocardium. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.