VEGF administration in chronic myocardial ischemia in pigs
VEGF administration in chronic myocardial ischemia in pigs
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DOI：
10.1016/s0008-6363(98)00136-9
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发表时间：
1998-11-01
影响因子：
10.8
通讯作者：
Simons, M
中科院分区：
文献类型：
--
作者：
Lopez, JJ;Laham, RJ;Simons, M
目的：以往的研究表明，血管内或血管外持续给予血管内皮生长因子（VEGF）在慢性心肌缺血中改善左心室功能的有效性。本研究旨在评价单次推注或局部冠状动脉内给药的疗效。方法：对约克郡猪放置左旋动脉Ameroid封堵器。三周后，将动物随机分配至通过局部冠状动脉内递送系统（InfusaSleeve（TM）n = 10）、冠状动脉内推注输注n = 7）或通过心外膜植入渗透递送系统（n = 7）完成的VEGF（20 μ g）治疗。另一组动物接受冠状动脉内注射生理盐水，并作为对照（n = 9）。治疗开始后3周，评价动物的心肌灌注和整体以及局部心室功能。结果如下：所有三个VEGF治疗组，但不是对照组动物，均显示左至左的显著增加。（但不是从右到左）侧支循环指数，心肌血流量（治疗前LCX与LAD（所有组的平均值）：0.76 +/- 0.35 vs. 0.96 +/- 0.38 ml*min（-1）*g（-1），p = 0.03;治疗后：LCX与LAD：1.16 +/- 0.39 vs. 1.15 +/- 0.28 ml*min（-1）*g（-1）p = NS）和生长因子给药后3周的冠状动脉血管舒张储备在所有VEGF治疗组中，观察到的VEGF诱导的灌注增加与局部心室功能的改善相关（治疗前vs.治疗后：i.c. VEGF 20 +/- 5.1 vs. 33 +/- 4.8;局部VEGF 16 +/- 2.8 vs. 33.6;泵VEGF 17 +/- 3.8 vs. 34 +/- 4.9 p
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 mu g) accomplished by local intracoronary delivery system (InfusaSleeve(TM) 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 ml*min(-1)*g(-1), p = 0.03; post-therapy: LCX vs. LAD: 1.16 +/- 0.39 vs. 1.15 +/- 0.28 ml*min(-1)*g(-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