Catheter-based myocardial gene transfer utilizing nonfluoroscopic electromechanical left ventricular mapping.
OBJECTIVE
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 microg/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 microg/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.
Division of Cardiovascular Research, St. Elizabeth's Medical Center, and Tufts University School of Medicine, Boston, Massachusetts, USA.
P R
PR
Vale
D W
DW
Losordo
T
T
Tkebuchava
D
D
Chen
C E
CE
Milliken
J M
JM
Isner
D000818:Animals; D006328:Cardiac Catheterization; D004594:Electrophysiology / Q000379:methods; D005240:Feasibility Studies; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D017202:Myocardial Ischemia / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D013552:Swine; D016276:Ventricular Function; D001616:beta-Galactosidase / Q000378:metabolism
D001616:beta-Galactosidase