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Transthoracic direct current shock facilitates intramyocardial transfection of naked plasmid DNA infused via coronary vessels in canines

Gene Therapy volume 13, pages 906–916 (2006)Cite this article

Abstract

Catheter-mediated, percutaneous, transluminal delivery of naked plasmid DNA (pDNA) into myocardium may offer a valuable strategy to heart diseases. Here, we examined whether clinically available transthoracic direct current (DC) shock improves intracoronary naked DNA transfection into myocardium. Plasmid vector encoding the GL3 luciferase was infused retrogradely into the coronary veins of beagle dogs, whereas another pDNA solution was infused into the left coronary artery. During and after these procedures, the coronary venous sinus was occluded by balloon, and transthoracic DC shock of 200 J was applied immediately after the infusions. Without DC shock, no remarkable increase in luciferase activity was demonstrated in any part of the left ventricular myocardium. In the presence of DC pulsation, significant luciferase expression was detected in the regions that were supplied by left anterior descending coronary artery (LAD), whereas the gene expression in the right coronary artery (RCA) regions was much less drastic. X-gal (5-bromo-4-chloro-3-indolyl-β-D-galactoside) staining of cardiac cross-sections also revealed regional expression of β-galactosidase. Immunohistochemical examinations of heart cryosections revealed that cardiomyocytes in LAD regions successfully expressed transgene product. The present system may enable a new strategy for myocardial gene therapy, without any special device or technique other than cardiac catheterization and DC cardioversion that are generally performed in ordinary hospitals.

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Acknowledgements

We thank Drs Yoshiki Itokawa and Hiroshi Nakano (Departments of Surgery and Otorhinolaryngology, Kyoto Prefectural University of Medicine, respectively) for assisting in the animal experiments.

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Author notes

  1. Y Iida, Y Oda, S Nakamori and S Tsunoda: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Cardiology and Vascular Regenerative Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Y Iida, Y Oda, S Nakamori, S Tsunoda & H Matsubara

  2. Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Y Iida, S Nakamori, S Tsunoda, T Kishida, M Shin-Ya, H Asada, J Imanishi & O Mazda

  3. Louis Pasteur Center for Medical Research, Kyoto, Japan

    T Kishida

  4. Department of Cardiovascular Surgery, Saitama Medical Center, Kawagoe, Saitama, Japan

    S Gojo

  5. Department of Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    T Yoshikawa

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  1. Y Iida
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  2. Y Oda
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Correspondence to O Mazda.

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Iida, Y., Oda, Y., Nakamori, S. et al. Transthoracic direct current shock facilitates intramyocardial transfection of naked plasmid DNA infused via coronary vessels in canines. Gene Ther 13, 906–916 (2006). https://doi.org/10.1038/sj.gt.3302742

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