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

Eugenio Cingolani, Kristine Yee, Michael Shehata, Sumeet S. Chugh, Eduardo Marbán, Hee Cheol Cho

Research output: Contribution to journalArticlepeer-review

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 (KAAA + 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 KAAA + 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 AAA + H2 group compared with the control (P AAA + H2 (or its individual vectors) into the ventricular myocardium failed to elicit significant pacemaker activity. Conclusions: The right-sided delivery of KAAA + 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.

Original languageEnglish (US)
Pages (from-to)1310-1318
Number of pages9
JournalHeart Rhythm
Volume9
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Biological pacemaker
  • In vivo gene transfer
  • Pacemaker device infection
  • Preclincal large animal model
  • Temporary pacing

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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