Biological pacemaker created by percutaneous gene delivery via venous catheters in a porcine model of complete heart block

Heart Rhythm. 2012 Aug;9(8):1310-8. doi: 10.1016/j.hrthm.2012.04.020. Epub 2012 Apr 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Biological Clocks / genetics*
  • Catheter Ablation
  • Disease Models, Animal
  • Electrophysiologic Techniques, Cardiac
  • Gene Transfer Techniques
  • Genetic Vectors*
  • Green Fluorescent Proteins
  • Heart Block / therapy*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels / genetics
  • Potassium Channels, Inwardly Rectifying / genetics
  • Swine

Substances

  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Kcnj10 (channel)
  • Potassium Channels, Inwardly Rectifying
  • Green Fluorescent Proteins