Percutaneous endocardial transfer and expression of genes to the myocardium utilizing fluoroscopic guidance

Experimental studies indicate that administration of angiogenic proteins or genes by the epicardial or intracoronary route can stimulate development o f new collateral vessels and improve myocardial perfusion. An endocardial c atheter-based approach to this therapy would obviate the need for surgery, while preserving the effectiveness of direct intramyocardial administration . Fluoroscopic guidance and prototype, preformed, coaxial catheters were us ed to examine the feasibility of percutaneous catheter-based adenovirus (Ad )-mediated gene transfer and expression in normal swine myocardium. The fea sibility of intramyocardial administration (100 mul/injection) of a radioco ntrast agent and black tissue dye to all regions of the left ventricle (sep tum, anterior, lateral, and inferior wall) was confirmed fluoroscopically a nd on postmortem examination. Injections of replication-deficient adenoviru s (10 injections of 10(11) particle units/100 mul each) coding for beta -ga lactosidase (Ad beta gal) or vascular endothelial growth factor (Ad(GV)VEGF 121.10) were administered to the left ventricular free wall to examine endo cardial based gene transfer and expression. beta -Galactosidase activity wa s detected by histochemical staining and quantitative assay in targeted reg ions of the myocardium. Regional VEGF expression was found to be significan tly greater in targeted regions (1.3 +/- 0.4 ng/mg protein) as compared wit h non-targeted regions (0.3 +/- 0.1 ng/mg protein) or regions injected with control (Ad beta gal) virus (0.2 +/- 0.03 ng/mg protein, P < 0.001). Cathe ter-based Ad mediated endocardial gene transfer and expression is feasible using percutaneous, fluoroscopically guided, preformed, coaxial catheters. This approach should be clinically useful to administer angiogenic genes to the ischemic myocardium. Cathet Cardiovasc Intervent 2001;52:260-266. (C) 2001 Wiley-Liss, Inc.