Percutaneous adenoviral gene transfer into porcine coronary arteries: Is catheter-based gene delivery adapted to coronary circulation?

Recombinant adenoviral (Ad) vectors represent an efficient gene transfer sy stem for targeting the cardiovascular system. Phenotypic modulation of coro nary vascular cells in vivo is, however, critically dependent on the effica cy of local delivery devices. Four local drug delivery catheters were teste d for intracoronary gene transfer efficiency: the Infiltrator (INF, n = 10) , the Crescendo (CRE, n = 10), the Infusasleeve (SLE, n = 8), and the Remed y balloon (channel balloon [CHA], n = 8), After balloon injury of the LAD, Ad vector containing the firefly luciferase cDNA (AdCMVluc, 1.5 x 10(10) pl aque-forming units) was administered at the site of injury. On day 4, tissu e samples from different regions in the heart and from the liver were assay ed for luciferase activity to evaluate local and systemic gene transfer. IN F, CRE, and SLE catheters showed higher transduction levels of the target L AD segment than did the CHA catheter (median luciferase activity = 4.2 x 10 (6), 11 x 10(6), and 1.3 x 10(6) light units [LU]/vessel versus 0.09 x 10(6 ) LU/vessel, respectively, p < 0.05), Luciferase activity was occasionally observed in nontarget tissues (right and left ventricular free wall, distal LAD, and liver) and was not significantly different between groups. The vi ral circulatory half-life was similar for the four groups (<1 min). Gene tr ansfer efficiency was positively correlated with the degree of injury for t he intralumenal catheters (CRE, SLE, and CHA) but was independent of the ve ssel wall injury for the intramural INF, Local drug delivery catheters enab le efficient vascular gene transfer in balloon-injured coronary arteries, a prerequisite for further development of intracoronary gene therapy for res tenosis.