Widespread regional myocardial transfection by plasmid encoding Del-1 following retrograde coronary venous delivery

This study quantifies myocardial transfection following percutaneous retrograde coronary venous delivery (RCVD) of a plasmid encoding human Del-1. RCVD of Del-1, GFP plasmid, or marker dye was conducted in 14 pigs. After selective cannulation of a coronary vein, a delivery site was confirmed by contrast injection and myocardial blush. Ten milliliters of plasmid hDel-1 or GFP was administered. Animals were euthanized 3 and 7 days post-RCVD. hDel-1 gene expression was evaluated by quantitative RT-PCR. An average myocardial expression of 4.5x10(5) copies hDel-1/mug total RNA was observed within the approximately 5 x 5 cm(2) target tissue of the left ventricle. GFP expression was detected by fluorescent microscopy. hDel-1 protein expression was confirmed by immunohistochemistry. Regionalized myocardial expression was found in all pigs. hDel-1 RNA was not found in distant tissues except in the three pigs with prominent venovenous washout (PVW). These levels were 3 to 4 log unites lower than those found in myocardium. Single retrograde coronary venous administration resulted in efficient regional myocyte transfection of hDel-1 and GFP. This method may be useful and clinically feasible for myocardial angiogenesis therapy.