Catheter-based intracoronary myocardial adenoviral gene delivery: Importance of intraluminal seal and infusion flow rate

Sitaram M. Emani, Ashish S. Shah, Michael K. Bowman, Sitaramesh Emani, Katrina Wilson, Donald D. Glower, Walter J. Koch

Research output: Contribution to journalArticle

Abstract

Although percutaneous, adenoviral-mediated intracoronary gene delivery to the heart has been demonstrated in some species, consistent and safe methodology is needed before clinical applicability is possible. In this study, we examine the effects of altering intracoronary flow rate and obtaining an adequate seal between the catheter and the coronary lumen on successful cardiac gene delivery and myocardial injury in both piglets and adult rabbits. To study the efficacy of in vivo myocardial gene transfer, we utilized adenoviral vectors containing either the β2-adrenergic receptor or β-galactosidase. The left circumflex coronary artery of piglets and the right coronary artery of rabbits were catheterized under fluoroscopic guidance and adenovirus solutions were injected using varying flow rates with or without balloon inflation. Successful transgene delivery to the heart was determined ∼1 week after coronary infusions. Histologic analysis was also performed in all animals to determine the extent of myocardial injury. Our results indicate that efficient and reproducible cardiac transgene expression utilizing intracoronary delivery is dependent upon the infusion flow rate and, in larger animals, requires an intraluminal seal. Excessive flow rate is associated with greater myocardial injury. Thus, conditions can be established and controlled to improve future investigational and clinical application of catheter-based intracoronary myocardial gene therapy.

Original languageEnglish (US)
Pages (from-to)306-313
Number of pages8
JournalMolecular Therapy
Volume8
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Catheters
Transgenes
Coronary Vessels
Wounds and Injuries
Galactosidases
Genes
Rabbits
Economic Inflation
Adenoviridae
Genetic Therapy
Adrenergic Receptors

Keywords

  • β-adrenergic
  • Gene therapy
  • Heart failure
  • Myocardium
  • Receptor

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Catheter-based intracoronary myocardial adenoviral gene delivery : Importance of intraluminal seal and infusion flow rate. / Emani, Sitaram M.; Shah, Ashish S.; Bowman, Michael K.; Emani, Sitaramesh; Wilson, Katrina; Glower, Donald D.; Koch, Walter J.

In: Molecular Therapy, Vol. 8, No. 2, 01.08.2003, p. 306-313.

Research output: Contribution to journalArticle

Emani, Sitaram M. ; Shah, Ashish S. ; Bowman, Michael K. ; Emani, Sitaramesh ; Wilson, Katrina ; Glower, Donald D. ; Koch, Walter J. / Catheter-based intracoronary myocardial adenoviral gene delivery : Importance of intraluminal seal and infusion flow rate. In: Molecular Therapy. 2003 ; Vol. 8, No. 2. pp. 306-313.
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