Sakakibara Yutaka, Tambara Keiichi, Sakaguchi Genichi, Lu Fanglin, Yamamoto Masaya, Nishimura Kazunobu, Tabata Yasuhiko, Komeda Masashi
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Eur J Cardiothorac Surg. 2003 Jul;24(1):105-11; discussion 112. doi: 10.1016/s1010-7940(03)00159-3.
Therapeutic angiogenesis using basic fibroblast growth factor (bFGF) in coronary artery disease has been documented in a number of papers. However, the effectiveness is discrepant among documents. In this study, we evaluated the distribution of bFGF in the rat heart by different administration methods, and investigated the efficacy of slow-released administration of bFGF using biodegradable hydrogel microspheres (bFGF microspheres) in a pig infarction model toward an enhanced coronary bypass surgery.
Heart failure due to myocardial infarction was induced in rats and pigs. In the rat study, free form of bFGF (central venous injection, intracoronary injection, and intramyocardial administration) and bFGF microspheres (intramyocardial administration) were given 4 weeks later. The remaining radioactivity of bFGF in the hearts was estimated 1, 24, and 72 h later. On the other hand, the pigs were randomized into two groups 4 weeks after myocardial infarction. While the control group (n=8) had gelatin hydrogel microspheres with saline, the FGF group (n=8) received bFGF microspheres in the left ventricular (LV) wall.
In the rat study, after intramyocardial administration of bFGF microspheres, more bFGF remained in the rat heart 72 h later compared with the other methods (P<0.0001). In the pig study, 4 weeks after the treatment, the FGF group had smaller LV diastolic diameter (48.7+/-5.3 vs. 56.7+/-5.2 mm, P<0.01) than the control group. LV end-systolic elastance was higher in the FGF group (2.96+/-1.2 vs. 1.06+/-0.3 mmHg/ml, P<0.01). In microscopic examinations, many neovessels were found in and around the scar tissue, and the vascular density in the FGF group was significantly higher (61.5+/-18.3 vs. 153.0+/-29.0/mm2, P<0.01). In addition, the infarcted LV walls were less expanded and more thickened in the FGF group.
Biodegradable hydrogel microspheres with bFGF improved LV function and inhibited LV remodeling by angiogenesis in pigs with chronic myocardial infarction. bFGF microspheres into ischemic myocardium may revascularize small ungraftable vessels and may potentially increase distal run-off when applied in coronary bypass surgery.
许多文献已记载了使用碱性成纤维细胞生长因子（bFGF）治疗冠状动脉疾病中的血管生成情况。然而，不同文献报道的疗效存在差异。在本研究中，我们通过不同给药方法评估了bFGF在大鼠心脏中的分布，并在猪梗死模型中研究了使用可生物降解水凝胶微球（bFGF微球）缓慢释放bFGF对增强冠状动脉搭桥手术的疗效。
在大鼠和猪中诱导心肌梗死所致的心力衰竭。在大鼠研究中，4周后给予游离形式的bFGF（中心静脉注射、冠状动脉内注射和心肌内给药）以及bFGF微球（心肌内给药）。1、24和72小时后估计心脏中bFGF的剩余放射性。另一方面，在心肌梗死后4周将猪随机分为两组。对照组（n = 8）给予含盐水的明胶水凝胶微球，FGF组（n = 8）在左心室（LV）壁接受bFGF微球。
在大鼠研究中，心肌内给予bFGF微球后，72小时后大鼠心脏中残留的bFGF比其他方法更多（P < 0.0001）。在猪研究中，治疗4周后，FGF组的左心室舒张直径（48.7±5.3 vs. 56.7±5.2 mm，P < 0.01）小于对照组。FGF组的左心室收缩末期弹性更高（2.96±1.2 vs. 1.06±0.3 mmHg/ml，P < 0.01）。在显微镜检查中，在瘢痕组织内和周围发现许多新血管，FGF组的血管密度显著更高（61.5±18.3 vs. 153.0±29.0/mm2，P < 0.01）。此外，FGF组梗死的左心室壁扩张较少且增厚较多。
含bFGF的可生物降解水凝胶微球可改善慢性心肌梗死猪的左心室功能并通过血管生成抑制左心室重塑。将bFGF微球注入缺血心肌可能使不可移植的小血管再血管化，并在应用于冠状动脉搭桥手术时可能增加远端血流。
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