Objective: To investigate the effects of autologous bone mesenchymal stem cells (MSC) transplantation on malignant arrhythmia induced by electrophysiological (EP) stimulation and cardiomyocyte ion channels remodeling in a mini-swine model of acute myocardial infarction (AMI).
Methods: Immediately after AMI (LAD occluded for 120 min), MSC (10 x 10(7), labeled by colloidal gold and co-cultivated with 5-azacytidine, 5-aza, n = 12) or equal volume saline (n = 10) were injected through over-the-wire (OTW) balloon in LAD at distal over D(1). EP stimulation is performed after 2 hours and 4 weeks in both groups to induce arrhythmia. The variance of heterogeneity of sodium currents (I(Na)) and I(Na) steady-state inactivation curves in different zones of infracted wall were investigated by patch clamp technology and the relationship between ionic channel and ventricular arrhythmia is analyzed.
Results: EP induced malignant ventricular arrhythmia (VT) rate was similar (MSC 75% vs. saline 90%, P = 0.455) at 2 hours post AMI and was significantly lower in MSC group (25% vs. 80%, P = 0.012) at 4 weeks post AMI. The Peak I(Na) current densities of the Endo, Media and Epi were significantly lower in MSC group [(-14.04 +/- 3.82) pA/pF, (-29.26 +/- 5.70) pA/pF, (-12.43 +/- 3.04) pA/pF] compared those in saline group [(-9.71 +/- 3.38) pA/pF, (-18.98 +/- 4.05) pA/pF, (-8.47 +/- 3.34) pA/pF, all P < 0.05]. The I(Na) steady-state inactivation curves of the Epi, Endo and Media in mini-swine with VT in MSC group [(-126.2 +/- 10.9) mV, (-106.7 +/- 11.9) mV, (-105.4 +/- 11.0) mV] were similar as those in saline group with VT [(-129.1 +/- 10.9) mV, (-112.2 +/- 9.9) mV, (-109.7 +/- 9.2) mV, all P > 0.05] while significantly lower compared to MSC group without VT [(-93.1 +/- 13.8) mV, (-95.2 +/- 15.5) mV, (-103.4 +/- 8.7) mV, all P < 0.05]. The multiple logistic regression analysis showed that I(Na) current density (RR = 1.449, 95% CI 1.276 - 2.079, P = 0.029) and I(Na) steady-state inactivation curves (RR = 1.092, 95% CI 1.008 - 1.917, P = 0.012) were the independent factors for reduced VT.
Conclusions: Autologous MSC attenuated malignant ventricular arrhythmia induced by EP at 4 weeks in mini-swine with AMI which might due to altered cardiomyocyte ion channels remodeling induced by MSC.