title: Adenovirus-catheter compatibility increases gene expression after delivery to porcine myocardium.
abstract: Endomyocardial injection of adenoviral gene vectors enables localized delivery to comprised myocardial tissue. However, many materials used in endomyocardial delivery catheters may not be compatible with adenoviral gene vectors. In this study, a series of catheter-based endocardial and epicardial (direct visualization) procedures were performed to assess catheter-adenovirus compatibility in an in vivo model. A standard Nitinol-stainless steel (Ni-SS) catheter was compared with a novel Stiletto catheter designed for improved biocompatibility. In 4 animals 40 endocardial injections of adenovirus encoding beta-galactosidase (beta-Gal) were performed with the 2 catheters. After sectioning of the hearts only 8 of 20 Ni-SS beta-Gal+ sites could be identified (40% retrieval) whereas 16 of the 20 Stiletto injection sites were identified (80%). Within these areas successful transfection was observed (12.2 +/- 4.0 beta-Gal+ cells/high-power field [HPF] in the Ni-SS group vs. 30.1 +/- 6.8 beta-Gal+ cells/HPF in the Stiletto group; p = 0.03). After epicardial delivery to distinct areas of the myocardium adenoviral delivery as assayed by beta-galactosidase protein activity was >21 +/- 16-fold (range, 5 to >43-fold) greater than after Stiletto delivery. In conclusion, this study highlights the importance of adenovirus-material compatibility in gene delivery to the myocardium. Efficiency was greater when using the catheter designed to enhance biocompatibility.
authors.affiliation: Boston Scientific Corporation, Natick, MA 01760, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Naimark
authors.forename: John J
authors.initials: JJ
authors.lastname: Lepore
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Klugherz
authors.forename: Zihua
authors.initials: Z
authors.lastname: Wang
authors.forename: T Sloane
authors.initials: TS
authors.lastname: Guy
authors.forename: Hashim
authors.initials: H
authors.lastname: Osman
authors.forename: Sina L
authors.initials: SL
authors.lastname: Moainie
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.forename: Guy
authors.initials: G
authors.lastname: Reed
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.forename: Maria
authors.initials: M
authors.lastname: Palasis
authors.forename: Michael S
authors.initials: MS
authors.lastname: Parmacek
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wilensky
mesh_terms: D000256:Adenoviridae; D000497:Alloys; D000818:Animals; D006328:Cardiac Catheterization; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000008:administration & dosage; D009206:Myocardium / Q000378:metabolism*; D013193:Stainless Steel; D013552:Swine
chemical_list: D000497:Alloys; D013193:Stainless Steel; C013616:nitinol