The application of local gene transfer to the investigation or therapy of coronary vascular disease will require high efficiency of gene transfer in vivo. This is a function of the technique of local drug delivery, the vector employed and the underlying vascular disease.We employed an adenoviral vector carrying the gene for p Galactosidase driven by the rous sarcoma virus promoter (Avl.PGal) and showed 80% of cultured pig vascular smooth muscle cells expressing the transgene (MOI 200). 4 large white landrace pigs (15-20 kg) underwent angioplasty of a single coronary artery, (left anterior descending (LAD), circumflex (Cx)) with a 3 m m balloon catheter (balloon to artery ratio 1.3). They were allowed to recover for 14 -21 days. Further angioplasty at the same angiographic site (3mm balloon, balloon to artery ration 1.3) and also of the proximal segment of the previously uninjured left coronary branch.Immediately after angioplasty approximately 1.5ml of a suspension of 4 x 108 pfu A v l . p a l was delivered to the site using a 2.75mm double skinned microporous balloon, the MIC2 catheter (Cordis). Three days later the animals were killed and the coronary arteries retrieved and placed in X-Gal prior to processing for histology.Previously injured vessels showed neointimal hyperplasia. Four of 7 vessels examined showed successful gene transfer as evidenced by prussian blue nuclear staining. Three of these four positive vessels had sustained a primary injury prior to gene transfer, the fourth had a pre-existing neointimal lesion. In three of the vessels medial nuclear staining was sparse and seen in relationship to angioplasty-induced dissection. In the pre-injured vesssel sparse neointima cells showed positive staining. In the fourth vessel, a primary injury with extensive dissection, the adventitial fibromyoblasts showed evidence of approximately 25% gene transfer. Vessels without evidence of gene transfer were generally larger, suggesting poor apposition of the delivery catheter. Distal myocyte staining (with myositis) implied that intralumenal delivery had occurred. ARTERY THE EFFECT OF PRE-ESISTING LESIONS.
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