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

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.