Enhancing myocardial plasmid expression by retrograde coronary venous delivery

Myocardial delivery of genes holds great promise for treating many heart diseases; however, the optimal delivery technique, which maximizes safety and efficacy, has not been established. Two delivery techniques were evaluated in swine; percutaneous retrograde coronary venous delivery (RCVD) and direct intramyocardial injection (IM). RCVD was performed in the anterior interventricular vein (AIV) with an end-hole occlusion balloon catheter. The plasmid gWiz, encoding beta-galactosidase (10 ml; 1 mg/ml), was injected using either manual high pressure (HP-RCVD; n = 5) or pressure wire-guided low pressure (LP-RCVD; n = 4). For the IM group (n = 4), beta-Gal plasmid (5 mg/ml) was injected at 10 sites (200 microl/site) in the anterior left ventricular wall. Animals were euthanized after 5 days. The percentage of beta-Gal expressing cells in the delivered region was higher in the HP-RCVD (0.26% +/- 0.05%) than the LP-RCVD (0.05% +/- 0.03%; P = 0.07) and IM groups (0.02% +/- 0.01%; P = 0.01). Myocardium from the HP-RCVD group contained 7- and 17-fold higher levels of beta-Gal activity than either LP-RCVD and IM groups, respectively (P = 0.05 for both). The results of this study confirm the safety and efficacy of RCVD for myocardial gene delivery.