Author + information
- Received May 11, 1999
- Revision received October 15, 1999
- Accepted December 2, 1999
- Published online March 15, 2000.
- Ran Kornowski, MD, FACC∗,†,‡,* (, )
- Martin B Leon, MD, FACC∗,†,‡,
- Shmuel Fuchs, MD∗,†,‡,
- Yoram Vodovotz, PhD∗,†,‡,
- Michael A Flynn, MSc†,
- David A Gordon, MD†,
- Anthony Pierre, BSc∗,†,‡,
- Imre Kovesdi, PhD‡,
- Joan A Keiser, PhD† and
- Stephen E Epstein, MD, FACC∗,†,‡
- ↵*Reprint requests and correspondence: Dr. Ran Kornowski, Experimental Pharmacology and Myocardial Revascularization Program, Cardiovascular Research Foundation, 110 Irving Street, Northwest, Suite 4B-1, Washington, DC 20010
To test the feasibility of myocardial angiogenic gene expression using a novel catheter-based transendocardial injection system.
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.
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 × 1010 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 × 1010 viral particles × 6 sites) and sacrificed at 24 h. Injection sites were identified with ultraviolet light by coinjection of fluorescent beads.
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).
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.
☆ This research was supported, in part, by grants from the Cardiovascular Research Foundation and The Pergament Cardiovascular Research Center, Washington Hospital Center, Washington, DC, and Biosense-Webster, Johnson and Johnson Inc., Warren, New Jersey; and Parke-Davis, Ann Arbor, Michigan.
- Received May 11, 1999.
- Revision received October 15, 1999.
- Accepted December 2, 1999.
- American College of Cardiology