Gene transfer for ischemic heart failure in a preclinical model

Kiyotake Ishikawa, Dennis Ladage, Lisa Tilemann, Kenneth Fish, Yoshiaki Kawase, Roger J. Hajjar

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Various emerging technologies are being developed for patients with heart failure. Well-established preclinical evaluations are necessary to determine their efficacy and safety. Gene therapy using viral vectors is one of the most promising approaches for treating cardiac diseases. Viral delivery of various different genes by changing the carrier gene has immeasurable therapeutic potential. In this video, the full process of an animal model of heart failure creation followed by gene transfer is presented using a swine model. First, myocardial infarction is created by occluding the proximal left anterior descending coronary artery. Heart remodeling results in chronic heart failure. Unique to our model is a fairly large scar which truly reflects patients with severe heart failure who require aggressive therapy for positive outcomes. After myocardial infarct creation and development of scar tissue, an intracoronary injection of virus is demonstrated with simultaneous nitroglycerine infusion. Our injection method provides simple and efficient gene transfer with enhanced gene expression. This combination of a myocardial infarct swine model with intracoronary virus delivery has proven to be a consistent and reproducible methodology, which helps not only to test the effect of individual gene, but also compare the efficacy of many genes as therapeutic candidates.

Original languageEnglish
Article numbere2778
JournalJournal of Visualized Experiments
Issue number51
DOIs
StatePublished - May 2011

Keywords

  • Gene therapy
  • Intracoronary injection
  • Ischemic heart failure
  • Issue 51
  • Medicine
  • Myocardial infarction
  • Viral vector

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