Patrice Tremble

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 β‐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), β‐Gal plasmid (5 mg/ml) was injected at 10 sites (200 μl/site) in the anterior left ventricular wall. Animals were euthanized after 5 days. The percentage of β‐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 β‐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.