title: Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins: comparison with surgical and percutaneous intramyocardial gene delivery.
abstract: OBJECTIVE
  We 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.
  
  
  BACKGROUND
  Intramyocardial 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.
  
  
  METHODS
  In 15 pigs, adenoviral vectors (Ad2-CMV beta-galactosidase [beta-gal] 5 x 10(9) pfu) were applied via surgical IMD (n = 5), PIMD (n = 5), and selective pressure-regulated retroinfusion (n = 5). Seven days after gene transfer, myocardial beta-gal expression was measured by ELISA.
  
  
  RESULTS
  Selective retroinfusion into the anterior cardiac vein substantially increased reporter gene expression (1,039 +/- 79 pg beta-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 beta-gal expression, particularly along the injection sites, while retroinfusion resulted in a more homogenous transmural gene expression.
  
  
  CONCLUSIONS
  Percutaneous 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.
authors.affiliation: Internal Medicine I, Grosshadern University Hospital, Munich, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Raake
authors.forename: Georges
authors.initials: G
authors.lastname: von Degenfeld
authors.forename: Rabea
authors.initials: R
authors.lastname: Hinkel
authors.forename: Robert
authors.initials: R
authors.lastname: Vachenauer
authors.forename: Torleif
authors.initials: T
authors.lastname: Sandner
authors.forename: Sabrina
authors.initials: S
authors.lastname: Beller
authors.forename: Martin
authors.initials: M
authors.lastname: Andrees
authors.forename: Christian
authors.initials: C
authors.lastname: Kupatt
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.forename: Peter
authors.initials: P
authors.lastname: Boekstegers
mesh_terms: D000256:Adenoviridae; D000818:Animals; D003331:Coronary Vessels; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D007150:Immunohistochemistry; D007262:Infusions, Intravenous / Q000379:methods; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D011312:Pressure; D013552:Swine; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase