Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models.
OBJECTIVE
To test the feasibility of myocardial angiogenic gene expression using a novel catheter-based transendocardial injection system.


BACKGROUND
Angiogenesis has been induced by direct injection of growth factors into ischemic myocardium during open-heart surgery. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without need of surgery.


METHODS
A new guidance system for intramyocardial therapy utilizes magnetic fields and catheter-tip sensors to locate a position in space and reconstruct three-dimensional left ventricular (LV) electromechanical maps without using fluoroscopy. A retractable 27G needle was coupled with the guidance system for LV transendocardial injection. In 12 pigs, the catheter was used to inject 0.1 ml of methylene-blue (MB) dye and 8 pigs had myocardial injections of adenoviral vector (1 x 10(10) particles per site) containing the LacZ transgene. Ten pigs underwent catheter-based transendocardial injection and six pigs were injected using transepicardial approach with the gene encoding adenovirus vascular endothelial growth factor-121 (Ad.VEGF121; 1 x 10(10) viral particles x 6 sites) and sacrificed at 24 h. Injection sites were identified with ultraviolet light by coinjection of fluorescent beads.


RESULTS
Overall, 138 of 152 attempted injection MB tracks (91%) were found after sacrifice. Tissue staining was 7.1+/-2.1 mm in depth and 2.3+/-1.8 mm in width. No animal had pericardial effusion or tamponade. In Ad.LacZ injected animals, gross pathology showed positive staining in injected zones, and histology confirmed positive myocyte staining. Adenovirus vascular endothelial growth factor-121 injected sites showed high levels of VEGF121 production that was of similar magnitude whether injected using the transendocardial (880.4+/-412.2 pg VEGF121/mg protein) or transepicardial (838.3+/-270 pg VEGF121/mg protein) delivery approach (p = 0.62).


CONCLUSIONS
Using this magnetic guidance catheter-based navigational system, transgenes can effectively be transfected into designated myocardial sites. Thus, if it is determined that direct intramyocardial injection of angiogenic factors enhances collateral function in patients, this less invasive catheter-based system offers a similar gene delivery efficiency and, thus, may have clear advantages compared with the surgically-based transepicardial injection approach.
Kornowski
R
R
Cardiovascular Research Foundation, Washington Hospital Center, Washington, DC 20010, USA. rxk3@mhg.edu
Leon
M B
MB
Fuchs
S
S
Vodovotz
Y
Y
Flynn
M A
MA
Gordon
D A
DA
Pierre
A
A
Kovesdi
I
I
Keiser
J A
JA
Epstein
S E
SE
D000818:Animals; D018780:Body Surface Potential Mapping / Q000295:instrumentation*; D006328:Cardiac Catheterization / Q000295:instrumentation*; D003326:Coronary Circulation / Q000235:genetics; D004699:Endocardium / Q000473:pathology; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000235:genetics; D004867:Equipment Design; D005240:Feasibility Studies; D018014:Gene Transfer Techniques / Q000295:instrumentation; D015316:Genetic Therapy / Q000295:instrumentation*; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation*; D007267:Injections; D008222:Lymphokines / Q000008:administration & dosage* / Q000235:genetics; D017202:Myocardial Ischemia / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010496:Pericardium / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors