Electromagnetic guidance for catheter-based transendocardial injection: A platform for intramyocardial angiogenesis therapy - Results in normal and ischemic porcine models
R. Kornowski et al., Electromagnetic guidance for catheter-based transendocardial injection: A platform for intramyocardial angiogenesis therapy - Results in normal and ischemic porcine models, J AM COL C, 35(4), 2000, pp. 1031-1039
Citations number
21
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
OBJECTIVES 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 fact
ors into ischemic myocardium during open-heart surgery.
METHODS Catheter-based. transendocardial injection of angiogenic factors ma
y provide equivalent benefit without need of surgery. A new guidance system
for intramyocardial therapy utilizes magnetic fields and catheter-tip sens
ors to locate a position in space and reconstruct three-dimensional left ve
ntricular (LV) electromechanical maps without using fluoroscopy. A retracta
ble 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 under
went catheter-based transendocardial injection and six pigs were injected u
sing transepicardial approach with the gene encoding adenovirus vascular en
dothelial growth factor-121 (Ad.VEGF(121); 1 X 10(10) viral particles X 6 s
ites) and sacrificed at 24 h. Injection sites were identified with ultravio
let 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 zone
s, and histology confirmed positive myocyte staining. Adenovirus vascular e
ndothelial growth factor-121 injected sites showed high levels of VEGF(121)
production that was of similar magnitude whether injected using the transe
ndocardial (880.4 +/- 412.2 pg VEGF(121)/mg protein) or transepicardial (83
8.3 +/- 270 pg VEGF(121)/mg protein) delivery approach (p = 0.62).
CONCLUSIONS Using this magnetic guidance catheter-based navigational system
, transgenes can effectively be transfected into designated myocardial site
s. Thus, if it is determined that direct intramyocardial injection of angio
genic 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 transepicardia
l injection approach. (C) 2000 by the American College of Cardiology.