Abstract 1350: Cardiomyoplasty Using Embryonic Cardiomyocytes Restores Electrical Stability to the Infarcted Mouse Heart
Background: Cellular replacement strategies after myocardial infarction are currently focussed on restoring primarily myocardial contractile function. The potential consequences of this approach on the electrical stability has been only little explored to date. We have therefore tested the ventricular vulnerability in mice after cryo-infarction and injection of embryonic cardiomyocytes, myoblasts and whole bone marrow cells.
Methods: 101 adult male mice (CD1; HIM:OF1) were electrophysiologically investigated (EPI) in vivo, using transvenous catheterization and atrial/ventricular stimulation. Inducibility of ventricular tachycardias (VT) was evaluated in all animals. 18 mice were non-infarcted animals (control), a left ventricular cryo-infarction of defined size (4mm) was induced in 83 mice, 11–14 days prior to EPI. 28 out of these remained untreated (cryo), 22 animals underwent transplantation of embryonic cardiomyocytes (eCM) in the infarcted area, in 16 mice skeletal myoblasts (SM) and in 17 mice whole bone marrow (wBM) were injected.
Results: No major differences were observed among the groups with regard to ECG and standard EPI parameters, despite a significantly shorter VRP in the SM group versus control, cryo and eCM (P<0.05) and in the wBM group versus control and eCM (P<0.05). 96.4% of cryo were susceptible to induction of VT. Transplantation of eCM reduced VT-inducibility in infarcted animals significantly (36.4%; p=0.0001) compared to control (wt: 38.9%). This effect was not found in all the other groups with significantly elevated VT-inducibility in the SM 93.8% and in wBM 82.4% (p>0.016 for all groups vs. control and eCM).
Conclusion: We conclude, that cell replacement with eCM in mouse reduces strongly electrical vulnerability after myocardial infarction. This protective effect is missing after the transfer of SM and wBM possibly pointing towards the importance of electrical coupling. The precise cellular mechanism responsible for this powerful protective effect is currently under investigation.