The feasibility and safety of transendocardial gene injection in canine using a multifunctional intracardiac echocardiography catheter.

ABSTRACT

BACKGROUND: Transendocardial gene delivery may expose patients to the risk of pericardial perfusion due to excessive needle injections. This study investigated the feasibility and safety of transendocardial gene injection using a newly developed multifunctional intracardiac echocardiography catheter. METHODS: This new system integrated intracardiac echocardiography, a retractable 29-G needle, and other accessories into a single catheter (10F) that could be delivered into the left ventricle via a retrograde aortic approach. In three canines, the catheter was used to inject 0.2 ml of Evan's blue; six canines received myocardial injections of plasmid containing the EGFP transgene. In addition, two canines received transendocardial injections of a pAdTrace-bFGF plasmid. All canines receiving gene delivery were sacrificed after 3 days. The hearts were harvested for gross, histological examination and gene expression assessment. RESULTS: This catheter provided visual guidance for accurate needle-tip positioning within the target myocardium; the needle position was subsequently confirmed by microbubble infusion. No animal had pericardial effusion or sustained ventricular arrhythmia. Tissue staining showed well-demarcated margins within the target myocardium. In animals injected with pEGFP-N1, confocal microscopy demonstrated successful gene expression. In zones where pAdTrace-bFGF was injected, immunohistochemistry also showed positive staining. Compared to normal tissue (0.38±0.04), RT-PCR showed high levels of bFGF expression (0.63±0.02) in the target area (P<0.01). CONCLUSIONS: Transendocardial gene injection using a multifunctional intracardiac echocardiography catheter is feasible and could improve procedure-related safety which may provide a new strategy for transgene delivery in future.