经皮心内膜 VEGF 基因治疗：MRI 引导的 3D 心肌应变的递药和特征描述。

Percutaneous transendocardial VEGF gene therapy: MRI guided delivery and characterization of 3D myocardial strain.

机构信息

Department of Radiology and Biomedical Imaging, 513 Parnassus Avenue, HSW207B, University of California, San Francisco, CA, USA.

出版信息

Int J Cardiol. 2010 Sep 3;143(3):255-63. doi: 10.1016/j.ijcard.2009.02.030. Epub 2009 Apr 5.

DOI:10.1016/j.ijcard.2009.02.030

PMID:19346019

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。