在猪慢性心肌缺血模型中给予血管内皮生长因子（VEGF）
VEGF administration in chronic myocardial ischemia in pigs.
作者信息
Lopez J J, Laham R J, Stamler A, Pearlman J D, Bunting S, Kaplan A, Carrozza J P, Sellke F W, Simons M
机构信息
Angiogenesis Research Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
出版信息
Cardiovasc Res. 1998 Nov;40(2):272-81. doi: 10.1016/s0008-6363(98)00136-9.
OBJECTIVE
Previous investigations have shown the effectiveness of sustained intra- or extravascular administration of vascular endothelial growth factor (VEGF) in chronic myocardial ischemia in improvement of left ventricular function. The present investigations were undertaken in order to evaluate efficacy of a single bolus or local intracoronary delivery.
METHODS
Yorkshire pigs underwent placement of a left circumflex artery ameroid occluder. Three weeks later the animals were randomized to treatment with VEGF (20 micrograms) accomplished by local intracoronary delivery system (InfusaSleeve, n = 10), intracoronary bolus infusion (n = 7) or by epicardial implantation of an osmotic delivery system (n = 7). An additional group of animals received intracoronary administration of saline and served as a control (n = 9). Three weeks after initiation of therapy, the animals were evaluated with regard to myocardial perfusion and global as well as regional ventricular function.
RESULTS
All three VEGF treatment groups but not the control animals demonstrated a significant increase in the left-to-left (but not right-to-left) collateral index, myocardial blood flow (pre-therapy LCX vs. LAD (average of all groups): 0.76 +/- 0.35 vs. 0.96 +/- 0.38 mlmin-1g-1, p = 0.03; post-therapy: LCX vs. LAD: 1.16 +/- 0.39 vs. 1.15 +/- 0.28 mlmin-1g-1, p = NS) and coronary vasodilatory reserve 3 weeks after growth factor administration. The observed increase in VEGF-induced perfusion correlated with improvement in regional ventricular function in all VEGF-treated groups (pre-therapy vs. post-therapy: i.c. VEGF 20 +/- 5.1 vs. 33 +/- 4.8; local VEGF 16 +/- 2.8 vs. 33.6; pump VEGF 17 +/- 3.8 vs. 34 +/- 4.9 p < 0.05 for all) but not control animals (21 +/- 3.3 vs. 27 +/- 5.8, p = NS).
CONCLUSION
Single intracoronary delivery (intravascular bolus or local delivery) of VEGF is effective in stimulating physiologically significant angiogenesis in porcine model of chronic myocardial ischemia.
目的
先前的研究表明，在慢性心肌缺血中持续血管内或血管外给予血管内皮生长因子（VEGF）可有效改善左心室功能。本研究旨在评估单次推注或冠状动脉局部给药的疗效。
方法
约克夏猪接受左旋支动脉阿梅洛氏闭塞器植入。三周后，将动物随机分为接受VEGF（20微克）治疗组，治疗方式分别为冠状动脉局部给药系统（InfusaSleeve，n = 10）、冠状动脉推注（n = 7）或经心外膜植入渗透给药系统（n = 7）。另一组动物接受冠状动脉内注射生理盐水作为对照（n = 9）。治疗开始三周后，对动物的心肌灌注、整体及局部心室功能进行评估。
结果
所有三个VEGF治疗组而非对照动物组，在生长因子给药三周后，左向左（而非右向左）侧支循环指数、心肌血流量（治疗前左旋支与前降支（所有组平均值）：0.76±0.35 vs. 0.96±0.38 ml·min⁻¹·g⁻¹，p = 0.03；治疗后：左旋支与前降支：1.16±0.39 vs. 1.15±0.28 ml·min⁻¹·g⁻¹，p = 无显著差异）和冠状动脉扩张储备均显著增加。在所有VEGF治疗组中，观察到的VEGF诱导的灌注增加与局部心室功能改善相关（治疗前与治疗后：冠状动脉内VEGF 20±5.1 vs. 33±4.8；局部VEGF 16±2.8 vs. 33.6；泵注VEGF 17±3.8 vs. 34±4.9，所有p < 0.05），但对照动物组无此现象（21±3.3 vs. 27±5.8，p = 无显著差异）。
结论
在慢性心肌缺血猪模型中，单次冠状动脉内给予（血管内推注或局部给药）VEGF可有效刺激具有生理意义的血管生成。
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