Vascular reactions to in vivo electroporation: Characterization and consequences for drug and gene delivery

Julie Gehl, Torben Skovsgaard, Lluis M. Mir

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    Abstrakt

    In vivo electroporation (EP) is gaining momentum for drug and gene delivery. In particular, DNA transfer by EP to muscle tissue can lead to highly efficient long-term gene expression. We characterized a vascular effect of in vivo EP and its consequences for drug and gene delivery. Pulses of 10-20 000 μs and 0.1-1.6 kV/cm were applied over hind- and forelimb of mice and perfusion was examined by dye injection. The role of a sympathetically mediated vasoconstrictory reflex was investigated by pretreatment with reserpine. Expression of a transferred gene (luciferase), permeabilization (determined using 51Cr-EDTA), membrane resealing and effects on perfusion were compared to assess the significance of the vascular effects. Above the permeabilization threshold, a sympathetically mediated Raynaud-like phenomenon with perfusion delays of 1-2 min was observed. Resolution of this phase followed kinetics of membrane resealing. Above a second threshold, irreversible permeabilization led to long perfusion delays. These vascular reactions (1) affect kinetics of drug delivery, (2) predict efficient DNA transfer, which is optimal during short perfusion delays, and (3) might explain electrocardiographic ST segment depressions after defibrillation as being caused by vascular effects of EP of cardiac muscle.

    OriginalsprogEngelsk
    Sider (fra-til)51-58
    Antal sider8
    TidsskriftBiochimica et Biophysica Acta - General Subjects
    Vol/bind1569
    Udgave nummer1-3
    DOI
    StatusUdgivet - 15 jan. 2002

    Fingeraftryk Udforsk hvilke forskningsemner 'Vascular reactions to in vivo electroporation: Characterization and consequences for drug and gene delivery' indeholder.

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