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

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.

A new agent for atrial fibrillation: electrophysiological properties of dronedarone.

Although originally synthesized as an antianginal compound, amiodarone has emerged as an effective antiarrhythmic for both supraventricular and ventricular arrhythmias. Over the decades, the properties, the effectiveness, the merits as well as the shortcomings of the compound have been well established. The major limitations of this agent are mainly due to the systemic side effects seen with prolonged therapy. Many of the toxic effects observed are primarily caused by the high iodine content present in the amiodarone molecule. Dronedarone, the first noniodinated amiodarone congener, has been developed largely to obtain the antiarrhythmic efficacy in the control of atrial fibrillation without the known adverse side effects of dronedarone. In this part of the supplement, the focus is the electrophysiological effects of dronedarone with the characterization in normal cardiac cells, in animal models of disease, as well as in human studies.