Transplanted neonatal cardiomyocytes as a potential biological pacemaker in pigs with complete atrioventricular block

Background. Sinus node dysfunction and severe heart block are major indications for electronic pacemaker implantation. The aim of the present study was to investigate the feasibility of an alternative approach by using spontaneously excitable cell grafts to serve as a biological pacemaker. Methods. Enzymatically isolated neonatal atrial cardiomyocytes (including sinus nodal cells) were grafted into the free wall of the left ventricle of 5 male pigs. In the control group (n=4), the medium was used for injecting. Three weeks after the transplantation the pigs underwent catheter ablation of the atrioventricular (AV) node. Microelectrode technique was used to record the transmembrane action potential of myocytes from cell- and medium-injected preparations. Immunohistochemistry was used to verify the grafted cells and the establishment of the gap junctions between donor and host cardiomyocytes. Results. After the creation of complete AV-block, a higher average idioventricular rate was observed in cell-grafted pigs than that in control pigs (89 +/- 13 vs. 30 +/- 11 bpm, P < 0.05). Administering isoprenaline caused a significant increase in the idioventricular rate from 89 13 to 120 18 bpm in the cell-grafted animals (P < 0.05). Microelectrode recordings showed that the spontaneously beating rate was significantly higher in the cell-implanted than that in the control preparations (82 +/- 17 vs. 33 +/- 13 bpm, P < 0.05). Furthermore, the immuno fluorescence microscopy identified the DAPI-labeled donor cells, and the connexin-43 and N-cadherin positive junctions between them and host cardiomyocytes. Conclusion. Grafted neonatal atrial cardiomyocytes are able to survive and integrate into the host myocardium, and show a pacing function that can be modulated by autonomic agents.