Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins

Catheter-based percutaneous transluminal gene delivery (PTGD) into the coro nary artery still falls behind the expectations of an efficient myocardial gene delivery system. In this study gene delivery was applied by selective pressure-regulated retroinfusion through the coronary veins to prolong adhe sion of replication defective adenovirus within the targeted myocardium. Ad enoviral vectors consisted either of luciferase (Ad.rsv-Luc) or beta-galact osidase (Ad.rsv-beta Gal) reporter gene under control of an unspecific prom otor derived from the Rous sarcoma virus (RSV). In this pig model, selectiv e retrograde gene delivery into the anterior cardiac vein during a brief pe riod of ischemia substantially increased reporter gene expression in the ta rgeted myocardium (LAD region) compared with antegrade delivery as a contro l. Repeated retrograde delivery during two periods of brief ischemia result ed in a more homogeneous transmural expression predominantly observed in ca rdiomyocytes (X-gal-staining). In the nontargeted myocardium (CX region) th ere was no evidence for adenoviral transfection. From our data we infer tha t selective pressure-regulated retroinfusion is a promising approach for ef ficient percutaneous transluminal gene delivery to the myocardium.