title: In vivo electroporation mediated gene delivery to the beating heart.
abstract: Gene therapy may represent a promising alternative strategy for cardiac muscle regeneration. In vivo electroporation, a physical method of gene transfer, has recently evolved as an efficient method for gene transfer. In the current study, we investigated the efficiency and safety of a protocol involving in vivo electroporation for gene transfer to the beating heart. Adult male rats were anesthetised and the heart exposed through a left thoracotomy. Naked plasmid DNA was injected retrograde into the transiently occluded coronary sinus before the electric pulses were applied. Animals were sacrificed at specific time points and gene expression was detected. Results were compared to the group of animals where no electric pulses were applied. No post-procedure arrhythmia was observed. Left ventricular function was temporarily altered only in the group were high pulses were applied; CK-MB (Creatine kinase) and TNT (Troponin T) were also altered only in this group. Histology showed no signs of toxicity. Gene expression was highest at day one. Our results provide evidence that in vivo electroporation with an optimized protocol is a safe and effective tool for nonviral gene delivery to the beating heart. This method may be promising for clinical settings especially for perioperative gene delivery.
authors.affiliation: Department of Cardiovascular Surgery, University Hospital of Berne, Berne, Switzerland.
authors.forename: Erick L
authors.initials: EL
authors.lastname: Ayuni
authors.forename: Amiq
authors.initials: A
authors.lastname: Gazdhar
authors.forename: Marie Noelle
authors.initials: MN
authors.lastname: Giraud
authors.forename: Alexander
authors.initials: A
authors.lastname: Kadner
authors.forename: Mathias
authors.initials: M
authors.lastname: Gugger
authors.forename: Marco
authors.initials: M
authors.lastname: Cecchini
authors.forename: Thierry
authors.initials: T
authors.lastname: Caus
authors.forename: Thierry P
authors.initials: TP
authors.lastname: Carrel
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Schmid
authors.forename: Hendrik T
authors.initials: HT
authors.lastname: Tevaearai
mesh_terms: D000818:Animals; D018274:Electroporation; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000628:therapy; D006439:Hemodynamics; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology; D010957:Plasmids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000502:physiology