Publications

Percutaneous Endocardial Infusion of Plasmids Using Helical Needle Catheter

Didier Rouy 1, Mehrad Rezaee 2, Nicolas Borenstein 3, Peter Altman 4, Bertrand Schwartz 1

Objective: To evaluate the efficiency of helical endocardial infusion system for percutaneous catheter-based plasmid delivery to the porcine myocardium under standard fluoroscopy. Parameters studied were: 1) efficiency of gene transfer, using Luciferase as a reporter gene to quantify overall levels of expression; 2) tolerance of the injection process; 3) biocompatibility plasmid / catheter.

Methods: Three adult pigs were injected in the left ventricle myocardium with plasmids encoding luciferase using BioCardia catheter under fluoroscopic guidance. For each pig, 1mg of plasmid (1mg/ml in saline) was distributed in 10 injection sites (0.1 ml/site). Injected areas were identified on a 16 segment bull-eyes map. After the procedure, plasmid was flushed through the catheter and recovered for supercoiling analysis. Three days after injection, the animals were sacrificed, the hearts were grossly examined, and sampled according to the 16 segment bull-eyes map, for luciferase analysis.

Results: No serious adverse cardiac events were associated with the injection procedure: transient ECG abnormalities were observed during needle implantation, but normal rhythm resumed after needle removal. For all three pigs, the examination of the endocardium showed focused injection sites. Myocardium samples of the three animals injected with luciferase encoding plasmid were further analyzed for regional luciferase activity, and demonstrated consistent expression levels in 27 out of 30 injected samples. Post catheter analysis showed minimal loss of supercoiling after injection process.

Conclusion: The percutaneous helical endocardial infusion catheter system allowed intramyocardial injection of plasmid through an endomyocardial, catheter-mediated route. No serious adverse events were reported during the in vivo phase of the study. All pigs presented evidence of gene transfer into the injected left ventricular (LV) myocardium, demonstrating feasibility of targeted localized gene expression. Thus, endocardial catheter-based delivery of a plasmid using the BioCardia helical catheter was found to be feasible and efficient.

1 Gencell, a Division of Aventis, Aventis Pharma SA, Vitry / Seine, France
2 Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, United States
3 CERA, Paris, France
4 Biocardia Inc., South San Francisco, CA, United States

American Society of Gene Therapy, Boston, Massachusetts, June 7, 2002. Abstract No. 723