Thorac Cardiovasc Surg 2016; 64 - OP106
DOI: 10.1055/s-0036-1571559

Long-term Reduction of Post-infarct Ventricular Tachycardia by Direct Lentiviral Connexin 43 Gene Transfer

B. Engelbrecht 1, A. Klein 2, M. Breitbach 2, A. Parikh 3, J. Lee 4, K. Zimmermann 5, A. Ottersbach 2, D. Dürr 1, A. Welz 1, A. Pfeifer 5, G. Salama 3, M. Kotlikoff 4, B. K. Fleischmann 2, W. Röll 1
  • 1University of Bonn, Department of Cardiac Surgery, Bonn, Germany
  • 2University of Bonn, Department of Physiology I, Bonn, Germany
  • 3University of Pittsburgh, Department of Medicine, Heart and Vascular Institute and the McGowan Institute for Regenerative Medicine, Pittsburgh, United States
  • 4Cornell University, Department of Biomedical Sciences, College of Veterinary Medicine, Ithaca, United States
  • 5University of Bonn, Department of Pharmacology and Toxicology, Bonn, Germany

Objective: Re-entry ventricular tachycardias (VT) caused by varying conduction velocities of native and lesioned myocardium represent a frequent and potentially lethal complication in myocardial infarction. To modulate this conduction inhomogeneity lentivirus based transduction of resident cells within the lesion with the gap junction protein Connexin 43 (Cx43) was performed.

Methods: Cryolesions were generated within the free left ventricular wall of CD1 wild type (WT) mice. 2–3 days postoperatively the chest was reopened and lentiviral gene transfer was performed by direct intramyocardial injection of 5µl of CMV-Cx43-IRES-EGFP or CMV-EGFP lentivirus solution. In vivo electrophysiological investigation was performed two and eight weeks after myocardial infarction. Ventricular function was evaluated by LV catheterization or echocardiography. Furthermore hearts were analyzed morphologically and expression of the transgene was proven by qPCR.

Results: Direct lentiviral Cx43 transduction of the lesioned area resulted after two and eight weeks in significant protection against post-infarct VT. Cx43 expression was proven in (myo-) fibroblasts and non-cardiac cells within the scar area. Integration of the lentiviral constructs and expression of the encoded proteins within the infarct area was shown by qPCR and immunohistochemistry. Left ventricular function of CMV-Cx43-IRES-EGFP and CMV-EGFP treated animals was comparable.

Conclusions: Direct intramyocardial lentivirus based Cx43 gene transfer in acute myocardial infarction, represents a simple and clinically applicable biological therapy, which persistently reduces post-infarction VT. Left ventricular function is not altered.