Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins Comparison with surgical and percutaneous intramyocardial gene delivery

ObjectivesWe sought to study adenoviral gene delivery using percutaneous selective pressure-regulated retroinfusion and to compare it directly with surgical and percutaneous intramyocardial delivery (PIMD) for the first time.BackgroundIntramyocardial delivery (IMD) has been recommended to be the preferred gene delivery strategy so far. However, surgical and percutaneous intramyocardial injection lead to incomplete retention of the injected viral vectors and to limited spatial myocardial distribution. Percutaneous selective pressure-regulated retroinfusion of the coronary veins was developed recently to provide an effective and more homogenous regional myocardial gene transfer.MethodsIn 15 pigs, adenoviral vectors (Ad2-CMV beta-galactosidase [β-gal] 5 × 109pfu) were applied via surgical IMD (n = 5), PIMD (n = 5), and selective pressure-regulated retroinfusion (n = 5). Seven days after gene transfer, myocardial β-gal expression was measured by ELISA.ResultsSelective retroinfusion into the anterior cardiac vein substantially increased reporter gene expression (1,039 ± 79 pg β-gal/mg protein) in the targeted left anterior descending coronary artery territory when compared with surgical (448 ± 127, p < 0.05) and PIMD (842 ± 145, p < 0.05). Both IMD approaches showed an inhomogenous β-gal expression, particularly along the injection sites, while retroinfusion resulted in a more homogenous transmural gene expression.ConclusionsPercutaneous selective pressure-regulated retroinfusion compares favorably with surgical and percutaneous intramyocardial injection techniques by providing a more homogenous and even more efficient adenoviral gene delivery