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EXPERIMENTAL STUDIES

Catheter-based myocardial gene transfer utilizing nonfluoroscopic electromechanical left ventricular mapping

^a Division of Cardiovascular Research, St. Elizabeth’s Medical Center, and Tufts University School of Medicine, Boston, Massachusetts, USA

Manuscript received October 5, 1998; revised manuscript received February 2, 1999, accepted March 15, 1999.

Reprint requests and correspondence: Dr. Jeffrey M. Isner, St. Elizabeth’s Medical Center, 736 Cambridge Street, Boston, Massachusetts 02135
jisner{at}opal.tufts.com

OBJECTIVES

This study investigated the feasibility and safety of percutaneous, catheter-based myocardial gene transfer.

BACKGROUND

Direct myocardial gene transfer has, to date, required direct injection via an open thoracotomy.

METHODS

Electroanatomical mapping was performed to establish the site of left ventricular (LV) gene transfer. A steerable, deformable 7F catheter with a 27G needle, which can be advanced 3 to 5 mm beyond its distal tip, was then directed to previously acquired map sites, the needle was advanced, and injections were made into the LV myocardium.

RESULTS

In two pigs in which methylene blue dye was injected, discretely stained LV sites were observed at necropsy in each pig, corresponding to the injection sites indicated prospectively by the endocardial map. In six pigs in which the injection catheter was used to deliver plasmid using cytomegalovirus promoter/enhancer, encoding nuclear-specific LacZ gene (pCMV-nlsLacZ) (50 µg/ml) to a single LV myocardial region, peak beta-galactosidase activity after five days (relative light units [RLU], mean 135,333 ± 28,239, range = 31,508 to 192,748) was documented in the target area of myocardial injection in each pig. Percutaneous gene transfer of pCMV-nlsLacZ (50 µg/ml) was also performed in two pigs with an ameroid constrictor applied to the left circumflex coronary artery; in each pig, peak beta-galactosidase activity after five days (214,851 and 23,140 RLU) was documented at the injection site. All pigs survived until sacrifice, and no complications were observed with either the mapping or the injection procedures.

CONCLUSIONS

Percutaneous myocardial gene transfer can be successfully achieved in normal and ischemic myocardium without significant morbidity or mortality. These findings establish the potential for minimally invasive cardiovascular gene transfer.

Abbreviations and Acronyms   LV = left ventricle   LCx = left circumflex coronary artery   pCMV-nlsLacZ = plasmid using cytomegalovirus promoter/enhancer, encoding nuclear-specific LacZ gene   RLU = relative light units   VEGF = vascular endothelial growth factor

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