Widespread regional myocardial transfection by plasmid encoding Del-1 following retrograde coronary venous delivery

Dongming Hou, Fiona Maclaughlin, Mary Thiesse, Vipul R. Panchal, Bas C.A.M. Bekkers, Elizabeth A. Wilson, Pamela I. Rogers, Michael C. Coleman, Keith L. March

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Abstract

This study quantifies myocardial transfection following percutaneous retrograde coronary venous delivery (RCVD) of a plasmid encoding human Del-1. RCVD of Del-1, GFP plasmid, or marker dye was conducted in 14 pigs. After selective cannulation of a coronary vein, a delivery site was confirmed by contrast injection and myocardial blush. Ten milliliters of plasmid hDel-1 or GFP was administered. Animals were euthanized 3 and 7 days post-RCVD. hDel-1 gene expression was evaluated by quantitative RT-PCR. An average myocardial expression of 4.5 × 105 copies hDel-1/μg total RNA was observed within the approximately 5 × 5 cm2 target tissue of the left ventricle. GFP expression was detected by fluorescent microscopy. hDel-1 protein expression was confirmed by immunohistochemistry. Regionalized myocardial expression was found in all pigs. hDel-1 RNA was not found in distant tissues except in the three pigs with prominent venovenous washout (PVW). These levels were 3 to 4 log unites lower than those found in myocardium. Single retrograde coronary venous administration resulted in efficient regional myocyte transfection of hDel-1 and GFP. This method may be useful and clinically feasible for myocardial angiogenesis therapy.

Original languageEnglish (US)
Pages (from-to)207-211
Number of pages5
JournalCatheterization and Cardiovascular Interventions
Volume58
Issue number2
DOIs
StatePublished - Feb 1 2003

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Keywords

  • Drug administration
  • Gene therapy
  • Myocardium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Hou, D., Maclaughlin, F., Thiesse, M., Panchal, V. R., Bekkers, B. C. A. M., Wilson, E. A., Rogers, P. I., Coleman, M. C., & March, K. L. (2003). Widespread regional myocardial transfection by plasmid encoding Del-1 following retrograde coronary venous delivery. Catheterization and Cardiovascular Interventions, 58(2), 207-211. https://doi.org/10.1002/ccd.10417