Biological pacemaker created by fetal cardiomyocyte transplantation.

BACKGROUND

The aim of this study was to investigate the feasibility of an alternative approach to electronic pacemaker by using spontaneously excitable cell grafts as a biological pacemaker in a large animal model of complete atrioventricular block.

METHODS AND RESULTS

Dissociated male human atrial cardiomyocytes including sinus nodal cells were grafted into the free wall of the left ventricle in five female pigs. Three weeks after the injection of cell-grafted solution/control medium the pigs underwent catheter ablation of the atrioventricular node (AV-node). After complete AV block was created, the idioventricular beat rate was more rapid in cell-grafted pigs than that in control pigs (86+/-21 vs. 30+/-10 bpm; P<0.001). Administering of isoprenalin significantly increased idioventricular rate from 86+/-21 to 117+/-18 bpm in the cell-grafted animals (P<0.01). Electrophysiological mapping studies demonstrated that the idioventricular rhythm originated from the cell-injection site. Polymerase chain reaction verifying the existence of SRY DNA in the cell injection site indicated that the grafted male cells were survived. Furthermore, the connexin-43 and N-cadherin positive junctions between donor cardiomyocytes and host cells were identified.

CONCLUSION

Xenografted fetal human atrial cardiomyocytes are able to survive and integrate into the host myocardium, and show a pacing function that can be modulated by autonomic agents.