Catheter-based transendocardial myocardial gene transfer

Area of Science:

• Cardiovascular Research
• Gene Therapy
• Molecular Cardiology

Background:

• Local modulation of myocardial function via gene transfer or cell deposition offers a potential cardiac treatment strategy.
• Catheter-based transendocardial injection (NOGA) is explored for myocardial plasmid gene transfer.

Purpose of the Study:

• To investigate the morphological characteristics of myocardial plasmid gene transfer using catheter-based transendocardial injection.
• To assess the distribution and localization of gene expression within the myocardium after injection.

Main Methods:

• Left ventricular morphology, electrical, and mechanical characteristics were mapped in 3D.
• In pigs, injections of toluidine blue, saline with pCMV-LacZ (beta-galactosidase), and phVEGF-A165 were administered transendocardially.
• Gene expression was determined 3 days post-injection.

Main Results:

• Macroscopically, injection sites on the endocardial surface were accurately targeted.
• Transmyocardial injections of colorant and plasmid DNA were distributed randomly throughout the left ventricular wall.
• Gene expression of beta-galactosidase was observed in a localized myocardial volume (approx. 5x5x5 mm) around each injection site.
• Microscopically, transfected cells were primarily found at the injection scar's tip, with 10-20 cells per scar.

Conclusions:

• Magnetic guidance allows precise localization of myocardial gene transfer on the left ventricular endocardial surface.
• Gene expression within the myocardium is localized to the injection scar's distal tip and occurs randomly at various depths.
• This suggests limitations in achieving widespread, depth-specific gene delivery with the current transendocardial injection method.