ABSTRACT 93

EPICARDIAL PLASMID GENE TRANSFER BY MICROSEEDING

Michael Hsin, Reitu Agrawal, Scott Visovatti, Rita Laurence, Jon Wee, Jerome Sepic, Mark Eskander, Lawrence Cohn, Elof Eriksson, Lishan Aklog  Harvard Medical School, Boston, USA

Protocols for epicardial delivery of therapeutic products employing direct needle injections in beating hearts suffer from imprecision regarding location, depth and amount of product delivered. Here we evaluate the feasibility and efficiency of a microseeding device for in vivo delivery of plasmid expressing b-galactosidase gene to pig myocardium.

Materials and Methods
7 pigs underwent left thoracotomy. Plasmid DNA was delivered using a set of oscillating solid needles driven by a modified tattooing device to the circumflex territory (0.2-1mg, 2X2 cm2 area, 3mm depth), or by direct needle injection. 3 pigs underwent ameroid constrictor implantation on the circumflex artery 6 weeks previously to render them chroincally ischemic, the remainder had non-ischemic hearts. 3 days after microseeding the hearts were harvested for b-galactosidase expression staining.

Results
All microseeded myocardium showed b-galactosidase expression. Gross and microscopic analysis showed b-galactosidase staining with clearly defined margins, predetermined depth and more uniformly distributed expression compared to direct injection controls.

Conclusion
Microseeding provides controlled and precise epicardial gene delivery for normal and ischemic myocardium.