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.
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.