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

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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

Fingerprint

Skeletal Muscle
Extremities
Muscles
Injections
Edema
Plasmids
Staining and Labeling
Evans Blue
DNA
Muscle Cells
Histology
Neutrophils
Leukocytes
Immunohistochemistry
Macrophages
Membranes

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Toumi, H., Hegge, J., Subbotin, V., Noble, M., Herweijer, H., Best, T., & 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

Rapid intravascular injection into limb skeletal muscle : A damage assessment study. / Toumi, Hechmi; Hegge, Julia; Subbotin, Vladimir; Noble, Mark; Herweijer, Hans; Best, Thomas; Hagstrom, James E.

In: Molecular Therapy, Vol. 13, No. 1, 01.01.2006, p. 229-236.

Research output: Contribution to journalArticle

Toumi, H, Hegge, J, Subbotin, V, Noble, M, Herweijer, H, Best, T & Hagstrom, JE 2006, 'Rapid intravascular injection into limb skeletal muscle: A damage assessment study', Molecular Therapy, vol. 13, no. 1, pp. 229-236. https://doi.org/10.1016/j.ymthe.2005.07.699
Toumi, Hechmi ; Hegge, Julia ; Subbotin, Vladimir ; Noble, Mark ; Herweijer, Hans ; Best, Thomas ; Hagstrom, James E. / Rapid intravascular injection into limb skeletal muscle : A damage assessment study. In: Molecular Therapy. 2006 ; Vol. 13, No. 1. pp. 229-236.
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