Gene therapy with iNOS enhances regional contractility and reduces delayed contrast enhancement in a model of postischemic congestive heart failure

Abstract

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.