Abstract 3454: Biological Pacing by Implantation of Autologous Sinoatrial Node Cells into the Canine Right Ventricle
Introduction: Implantation of an electronic pacemaker is a widely utilized therapy for the treatment of bradyarrhythmias. We hypothesized that isolated, autologous sinoatrial nodal (SAN) cells implanted into the right ventricle (RV) provide reliable pacing activity. Our intent was to use the results as a comparator for our earlier studies of biological pacing using HCN2 genes expressed in adult human mesenchymal stem cells (hMSC).
Methods: Radiofrequency ablation was performed to induce complete heart block and electronic pacemakers were implanted in the RV of adult mongrel dogs. Individual SAN cells were isolated by enzymatic digestion and studied by patch clamp to confirm SAN identity. Dissociated SAN cells (3–5 x105 cells) were injected into the RV subepicardial free wall and injection site pace-mapping was performed with bipolar electrodes. Dogs were Holter monitored for 2 weeks. Implanted SAN pacemaker function was assessed by overdrive suppression and an IV epinephrine challenge. The RV injection site was harvested at termination and examined for viable SAN cells.
Results: A preliminary study of 6 control and 12 dogs with SAN cell implantation showed faster resting heart rates (HR) at 3 weeks post-implantation than control dogs (Control 44.4+/−1.2 bpm, X+/−SEM, vs. SAN 61+/−2.6 bpm, P<.05). 6 additional dogs with implanted SAN cells were studied in greater detail over a 2 week period. Dissociated SAN cells exhibited robust If (current density 4.3±0.6 pA/pF at -105 mV, n=13). 3/6 dogs had significant pacemaker function from implanted SAN cells. Torpedo-shaped Poincare plots of implanted SAN heart rates reflected minimal parasympathetic influence. The 3 dogs with pacemaker function showed an increase in HR to epinephrine at 1.5 mcg/kg/min (resting 43+/−1 bpm vs epinephrine 66+/−3 bpm, P<.05). Microscopic examination of the RV showed disaggregated SAN cells beating spontaneously.
Conclusions: In dogs receiving autologous implantation of SAN cells into the RV, the ventricular pacing rates and catecholamine responsiveness are no better than biological pacemakers derived from comparable numbers of hMSCs expressing HCN2 or adenovirus expressing HCN2 delivered to the ventricular wall or left bundle branch.