Improvement of myocardial contractility in a porcine model of chronic ischemia using a combined transmyocardial revascularization and gene therapy approach.
Improvement of myocardial contractility in a porcine model of chronic ischemia using a combined transmyocardial revascularization and gene therapy approach.
复制标题
使用联合经心肌血运重建和基因治疗方法改善慢性缺血猪模型的心肌收缩力。
DOI：
10.1016/j.jtcvs.2004.10.017
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Doukas,John
中科院分区：
文献类型：
--
作者：
Horvath,KeithA;Lu,ChiaYangJ;Robert,Emmanuel;Pierce,GlennF;Greene,Rodney;Sosnowski,BarbaraA;Doukas,John
本研究的目的是研究一种新的成纤维细胞生长因子-2基因制剂，从基于胶原的基质中提供腺病毒载体的局部和持续的可用性，方法采用腺病毒载体介导的成纤维细胞生长因子-2基因转染方法，将成纤维细胞生长因子-2基因转染心肌细胞，观察成纤维细胞生长因子-2基因转染心肌细胞后的生长情况（腺病毒成纤维细胞生长因子-2）配制在基于胶原的基质中。然后治疗33只动物的缺血区域。第1组采用CO2激光心肌血运重建术;第2组心肌内注射胶原基质中的腺病毒成纤维细胞生长因子-2;第3组采用基质腺病毒成纤维细胞生长因子-2和CO2激光心肌血运重建术联合治疗;第4组注射生理盐水配制的腺病毒成纤维细胞生长因子-2。通过超声心动图和电影磁共振成像评估基线左心室功能。治疗后6周重复研究。用抗-α-肌动蛋白免疫组织化学方法评估血管的发育情况。与单独使用任何一种治疗相比，经RTMAxrix腺病毒成纤维细胞生长因子-2+经心肌激光血管重建治疗的区域的小动脉发育增加了105%（P <0.05），与单独使用生理盐水配制的腺病毒成纤维细胞生长因子-2治疗相比，增加了390%（P <0.05）。基质腺病毒成纤维细胞生长因子-2+经心肌激光血运重建治疗区域的收缩力显著改善，通过心肌壁增厚测量。这种功能改善通过电影磁共振成像证实，其中在基质腺病毒成纤维细胞生长因子-2+经心肌激光血运重建术后，治疗节段的收缩性增加了90%。其他治疗提供了显着减少恢复心肌function. CONCLUSIONSSThe增加血管生成的结果基质腺病毒成纤维细胞生长因子-2基因治疗与CO2 transmyocardial激光血运重建术相结合是大于在任何单独的治疗。由于这种血管生成反应，心肌功能也随之改善。
OBJECTIVESThe purpose of this study was to investigate whether a novel fibroblast growth factor-2 gene formulation, providing a localized and sustained availability of the adenoviral vector from a collagen-based matrix, in combination with CO2transmyocardial laser revascularization would lead to an enhanced angiogenic response and improved myocardial function.METHODSFibroblast growth factor-2 gene was delivered by means of an adenoviral vector (adenoviral fibroblast growth factor-2) formulated in a collagen-based matrix. The ischemic areas of 33 animals were then treated. Group 1 was treated with CO2transmyocardial laser revascularization; group 2 was treated with intramyocardial injections of adenoviral fibroblast growth factor-2 in a collagen-based matrix; group 3 had a combination treatment of matrix adenoviral fibroblast growth factor-2 and CO2transmyocardial laser revascularization; and group 4 received injections with saline-formulated adenoviral fibroblast growth factor-2. Baseline left ventricular function was assessed by echocardiography and cine magnetic resonance imaging. Studies were repeated 6 weeks after treatment. Vascular development was assessed using anti-α-actin immunohistochemistry.RESULTSMatrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularization-treated areas had a 105% increase in arteriolar development versus either treatment alone (P < .05) and a 390% increase compared with saline-formulated adenoviral fibroblast growth factor-2 treatment alone (P < .05). Contractility was significantly improved in matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularization-treated areas as measured by myocardial wall thickening. This functional improvement was confirmed by cine magnetic resonance imaging, in which a 90% increase in the contractility of the treated segments was demonstrated after matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularation. The other treatments provided significantly less restoration of myocardial function.CONCLUSIONSThe increase in angiogenesis as a result of matrix adenoviral fibroblast growth factor-2 gene therapy in combination with CO2transmyocardial laser revascularization is greater than that seen in either therapy alone. A concomitant improvement in myocardial function was seen as a result of this angiogenic response.