title: Biological pacemaker created by percutaneous gene delivery via venous catheters in a porcine model of complete heart block.
abstract: BACKGROUND
  Pacemaker-dependent patients with device infection require temporary pacing while the infection is treated. External transthoracic pacing is painful and variably effective, while temporary pacing leads are susceptible to superinfection.
  
  
  OBJECTIVE
  To create a biological pacemaker delivered via venous catheters in a porcine model of complete heart block, providing a temporary alternative/adjunct to external pacing devices without additional indwelling hardware.
  
  
  METHODS
  Complete atrioventricular (AV) nodal block was induced in pigs by radiofrequency ablation after the implantation of a single-chamber electronic pacemaker to maintain a ventricular backup rate of 50 beats/min. An adenoviral vector cocktail (K(AAA) + H2), expressing dominant-negative inward rectifier potassium channel (Kir2.1AAA) and hyperpolarization-activated cation channel (HCN2) genes, was injected into the AV junctional region via a NOGA Myostar catheter advanced through the femoral vein.
  
  
  RESULTS
  Animals injected with K(AAA) + H2 maintained a physiologically relevant ventricular rate of 93.5 ± 7 beats/min (n = 4) compared with control animals (average rate, 59.4 ± 4 beats/min; n = 6 at day 7 postinjection; P <.05). Backup electronic pacemaker utilization decreased by almost 4-fold in the K(AAA) + H2 group compared with the control (P <.05), an effect maintained for the entire 14-day window. In contrast to the efficacy of gene delivery into the AV junctional region, open-chest, direct injection of K(AAA) + H2 (or its individual vectors) into the ventricular myocardium failed to elicit significant pacemaker activity.
  
  
  CONCLUSIONS
  The right-sided delivery of K(AAA) + H2 to the AV junctional region provided physiologically relevant biological pacing over a 14-day period. Our approach may provide temporary, bridge-to-device pacing for the effective clearance of infection prior to the reimplantation of a definitive electronic pacemaker.
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California 90048, USA.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Cingolani
authors.forename: Kristine
authors.initials: K
authors.lastname: Yee
authors.forename: Michael
authors.initials: M
authors.lastname: Shehata
authors.forename: Sumeet S
authors.initials: SS
authors.lastname: Chugh
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
authors.forename: Hee Cheol
authors.initials: HC
authors.lastname: Cho
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D017115:Catheter Ablation; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006327:Heart Block / Q000628:therapy*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D013552:Swine; D000098854:Kcnj10 Channel
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D049452:Green Fluorescent Proteins