Department of Medicine II, Johannes Gutenberg-University Mainz, Mainz, Germany.
Clin Hemorheol Microcirc. 2011;49(1-4):271-8. doi: 10.3233/CH-2011-1477.
The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia.
Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control.
The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. Wall thickness at end-systole (6.8 mm vs. 5.9 mm, p < 0.001) and at end-diastole (5.4 mm vs. 4.2 mm, p < 0.001) were significantly higher in the therapy group. Additionally, the regional wall motion at the level of the ischemic region was 3.5 mm in the therapy group while it was significantly less (3.0 mm, p < 0.001) in the control group.
Our findings demonstrate that transient iNOS overexpression potentially leads to a significant decrease of regional late enhancement with a positive effect on regional cardiac function in the ischemic area in a large animal model of postischemic heart failure.
本研究旨在评估瞬时局部心肌基因转移诱导型一氧化氮合酶 (iNOS) 对慢性缺血诱导的心力衰竭大哺乳动物动物模型心功能的影响。
16 头长白猪采用微创模型诱导慢性心肌缺血。在心力衰竭表现出现后，8 头动物通过局部心肌内注射脂质体介导的 iNOS 基因转移进行治疗；8 头动物接受假手术作为对照。
iNOS 治疗组缺血区的晚期增强透壁率（对照组：46.4%，iNOS：35.9%；p<0.05）显著降低。收缩末期壁厚度（6.8 毫米对 5.9 毫米，p<0.001）和舒张末期壁厚度（5.4 毫米对 4.2 毫米，p<0.001）在治疗组明显更高。此外，治疗组缺血区的节段壁运动为 3.5 毫米，而对照组明显更低（3.0 毫米，p<0.001）。
我们的研究结果表明，瞬时 iNOS 过表达可能导致局部晚期增强显著减少，并对缺血后心力衰竭大动物模型缺血区的局部心功能产生积极影响。
