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Optical capture and defibrillation in rats with monocrotaline-induced myocardial fibrosis 1 year after a single intravenous injection of adeno-associated virus channelrhodopsin-2

  • Author Footnotes
    1 Drs Jianyi Li and Long Wang contributed equally to this study.
    Jianyi Li
    Footnotes
    1 Drs Jianyi Li and Long Wang contributed equally to this study.
    Affiliations
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

    Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

    Hubei Key Laboratory of Cardiology, Wuhan, People’s Republic of China
    Search for articles by this author
  • Author Footnotes
    1 Drs Jianyi Li and Long Wang contributed equally to this study.
    Long Wang
    Footnotes
    1 Drs Jianyi Li and Long Wang contributed equally to this study.
    Affiliations
    Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

    Hubei Key Laboratory of Cardiology, Wuhan, People’s Republic of China

    Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
    Search for articles by this author
  • Junmiao Luo
    Affiliations
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

    Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

    Hubei Key Laboratory of Cardiology, Wuhan, People’s Republic of China
    Search for articles by this author
  • Haitao Li
    Affiliations
    Department of Cardiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, People’s Republic of China
    Search for articles by this author
  • Panpan Rao
    Affiliations
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

    Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

    Hubei Key Laboratory of Cardiology, Wuhan, People’s Republic of China
    Search for articles by this author
  • Yue Cheng
    Affiliations
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

    Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

    Hubei Key Laboratory of Cardiology, Wuhan, People’s Republic of China
    Search for articles by this author
  • Xi Wang
    Correspondence
    Address reprint requests and correspondence: Dr Xi Wang, Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Pengliuyang Rd 228, Wuhan, Hubei 430060, PR China.
    Affiliations
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

    Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

    Hubei Key Laboratory of Cardiology, Wuhan, People’s Republic of China
    Search for articles by this author
  • Congxin Huang
    Correspondence
    Dr Congxin Huang, Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Pengliuyang Rd 228, Wuhan, Hubei 430060, PR China.
    Affiliations
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

    Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

    Hubei Key Laboratory of Cardiology, Wuhan, People’s Republic of China
    Search for articles by this author
  • Author Footnotes
    1 Drs Jianyi Li and Long Wang contributed equally to this study.
Published:August 08, 2020DOI:https://doi.org/10.1016/j.hrthm.2020.08.002

      Background

      Optogenetics uses light to regulate cardiac rhythms and terminate malignant arrhythmias.

      Objective

      The purpose of this study was to investigate the long-term validity of optical capture properties based on virus-transfected channelrhodopsin-2 (ChR2) and evaluate the effects of optogenetic-based defibrillation in an in vivo rat model of myocardial fibrosis enhanced by monocrotaline (MCT).

      Methods

      Fifteen infant rats received jugular vein injection of adeno-associated virus (AAV). After 8 weeks, 5 rats were randomly selected to verify the effectiveness ChR2 transfection. The remaining rats were administered MCT at 11 months. Four weeks after MCT, the availability of 473-nm blue light to capture heart rhythm in these rats was verified again. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were induced by burst stimulation on the basis of enhanced myocardial fibrosis, and the termination effects of the optical manipulation were tested.

      Results

      Eight weeks after AAV injection, there was ChR2 expression throughout the ventricular myocardium as reflected by both fluorescence imaging and optical pacing. Four weeks after MCT, significant myocardial fibrosis was achieved. Light could still trigger the corresponding ectopic heart rhythm, and the pulse width and illumination area could affect the light capture rate. VT/VF was induced successfully in 1-year-observation rats, and the rate of termination of VT/VF under light was much higher than that of spontaneous termination.

      Conclusion

      Viral ChR2 transfection can play a long-term role in the rat heart, and light can successfully regulate heart rhythm and defibrillate after cardiac fibrosis.

      Keywords

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