Document Detail

Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models.
MedLine Citation:
PMID:  10732905     Owner:  NLM     Status:  MEDLINE    
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 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.
R Kornowski; M B Leon; S Fuchs; Y Vodovotz; M A Flynn; D A Gordon; A Pierre; I Kovesdi; J A Keiser; S E Epstein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  35     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-03-31     Completed Date:  2000-03-31     Revised Date:  2007-05-02    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1031-9     Citation Subset:  AIM; IM    
Cardiovascular Research Foundation, Washington Hospital Center, Washington, DC 20010, USA.
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MeSH Terms
Body Surface Potential Mapping / instrumentation*
Coronary Circulation / genetics
Endocardium / pathology
Endothelial Growth Factors / administration & dosage*,  genetics
Equipment Design
Feasibility Studies
Gene Therapy / instrumentation*
Gene Transfer Techniques / instrumentation
Heart Catheterization / instrumentation*
Image Processing, Computer-Assisted / instrumentation*
Lymphokines / administration & dosage*,  genetics
Myocardial Ischemia / genetics,  pathology,  therapy*
Pericardium / pathology
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Reg. No./Substance:
0/Endothelial Growth Factors; 0/Lymphokines; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors

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