Rapid intravascular injection into limb skeletal muscle: A damage assessment study

Hechmi Toumi, Julia Hegge, Vladimir Subbotin, Mark Noble, Hans Herweijer, Thomas M. Best, James E. Hagstrom

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

We have recently developed a simple and highly efficient methodology for delivering plasmid DNA (pDNA) to skeletal muscle cells of mammalian limbs. The procedure involves the rapid intravascular injection of a large volume of saline (containing pDNA) into the vasculature of the distal limb. As a result of the robust delivery methodology involved, it is important to understand the effects of the injection procedure on the skeletal muscle tissue in the targeted limb. In previous studies, only modest and transient muscle damage was noted. In this study we quantitatively assessed the degree of muscle damage in rat limbs following intravascular injections using muscle histology (H&E staining), membrane integrity (Evans blue staining), and leukocyte infiltration (immunohistochemistry) assays. The rapid extravasation of fluid during the injection process resulted in edema of the muscle tissue of the targeted limb; however, the edema was transient and resolved within 24 h. Consistent with observations from previous studies, minimal levels of myofiber damage were detected. Immunohistochemical labeling indicated that increased numbers of neutrophils (CD43+) and macrophages (ED1+ and ED2+) were present in the muscle tissue interstitium shortly after injection but that elevations were relatively modest and resolved by 2 weeks postinjection.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalMolecular Therapy
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Toumi, H., Hegge, J., Subbotin, V., Noble, M., Herweijer, H., Best, T. M., & Hagstrom, J. E. (2006). Rapid intravascular injection into limb skeletal muscle: A damage assessment study. Molecular Therapy, 13(1), 229-236. https://doi.org/10.1016/j.ymthe.2005.07.699