Department of Radiology and Biomedical Imaging, 513 Parnassus Avenue, HSW207B, University of California, San Francisco, CA, USA.
Int J Cardiol. 2010 Sep 3;143(3):255-63. doi: 10.1016/j.ijcard.2009.02.030. Epub 2009 Apr 5.
Patients with myocardial infarcts have unfavorable left ventricular (LV) remodeling and devastating outcomes. This study was performed to determine whether VEGF-gene delivered transendocardially under MR-guidance improves LV three-dimensional (3D) strain (circumferential, longitudinal and radial), reduces infarct transmurality and increases vascular density in a canine model of permanent LAD coronary artery occlusion.
Imaging was performed using a 1.5-T MR scanner. Three days after occlusion, a percutaneous catheter was advanced under MR-guidance into the LV chamber for transendocardial delivery of VEGF-gene therapy (n=6) or LacZ-gene as control (n=6) into infarcted and peri-infarcted myocardium. MRI was performed before (3 days) and after (50 days) the delivery of therapy using cine, tagged and delayed contrast enhancement. Histochemical and pathological stains were used to assess myocardial viability and vascular density, respectively.
Transendocardial delivery of VEGF-gene therapy and LacZ-gene under MRI guidance was successful in all animals. Significant improvement in 3D strain was observed within 50 days in treated animals. On the other hand, control animals demonstrated deterioration in regional strain over time. Significant reductions in infarct transmurality and increases in capillary and arteriole densities were also observed in VEGF-treated as compared to control animals.
MR-guided transendocardial delivery of VEGF-gene improved myocardial strain and enhanced transmural infarct resorption. This minimally invasive technique may be useful for delivery of local therapies, designed to promote angiogenesis or myogenesis.
心肌梗死患者的左心室（LV）重构不良，预后较差。本研究旨在确定在磁共振（MR）引导下经心内膜递送 VEGF 基因是否能改善犬永久性左前降支冠状动脉闭塞模型的 LV 三维（3D）应变（环向、纵向和径向），减少梗死透壁性，并增加血管密度。
使用 1.5-T MR 扫描仪进行成像。闭塞后 3 天，在 MR 引导下将经皮导管推进 LV 腔，将 VEGF 基因治疗（n=6）或 LacZ 基因作为对照（n=6）递送至梗死和梗死周边心肌。在治疗前（3 天）和治疗后（50 天）使用电影、标记和延迟对比增强进行 MRI 检查。组织化学和病理染色分别用于评估心肌活力和血管密度。
在所有动物中，经心内膜递送 VEGF 基因治疗和 LacZ 基因在 MRI 引导下均获得成功。治疗动物在 50 天内观察到 3D 应变明显改善。另一方面，对照动物的区域应变随时间恶化。与对照动物相比，VEGF 治疗组的梗死透壁性降低和毛细血管及小动脉密度增加也更为明显。
MR 引导下经心内膜递送 VEGF 基因可改善心肌应变，增强透壁性梗死吸收。这种微创技术可能有助于局部治疗的递送，旨在促进血管生成或肌生成。
