Adenoviral-mediated gene transfer in human and animal vein grafts using clinically relevant exposure times, pressures, and viral concentrations

This study examined the efficiency of adenoviral-mediated gene transfer in experimental vein grafts and cultured human saphenous vein under physiologi c: conditions using clinically relevant exposure times, pressures, and vira l concentrations. The external jugular veins of 25 male New Zealand White r abbits were exposed to 0.5 mL of replication-deficient adenovirus vectors e ncoding beta -galactosidase (AdlacZ), control adenovirus (AdBglll), or vehi cle at pressures ranging from 0 to 120 mmHg for 10 min. Veins were excised and grafted into the carotid circulation. After 5 days, the vessels were re exposed, excised, and stained with X-gal chromagen for beta -galactosidase (beta -gal) activity. Gene transfer was also performed in 13 segments of hu man saphenous vein discarded at the time of bypass grafting. The veins were cultured for 0-21 days and assayed for beta -gal activity as above. Rabbit vein grafts exposed to high-pressure AdlacZ transfection showed significan t transgene expression in 100% of grafts (39 +/- 2% positive cells/hpf) whi le only 60% of those transfected at low pressure expressed beta -gal (9 +/- 3% positive cells/hpf). All human veins exposed to AdlacZ expressed beta - gal to a variable degree (range 10-50% positive cells/hpf). No control graf ts or veins expressed the transgene. Efficient adenoviral-mediated gene tra nsfer in experimental vein grafts and human saphenous vein segments can be achieved using clinically feasible parameters of exposure time, pressure, a nd viral concentration.