Objective Concerns that intramyocardial delivery of immature cells could cause potentially life-threatening ventricular arrhythmias have been repeatedly raised. The aim of this study is to investigate the electrophysiological and arrhythmogenic effects for MSCs therapy in AMI.
Methods GFP tagged MSCs were injected into a murine heart with left anterior descending (LAD) ligation. Two weeks after transplantation, effective refractory period (ERP), ventricular arrhythmias (VAs) inducibility and ventricular fibrillation threshold (VFT) were assessed by programmed electrical stimulation (PES), respectively. Epicardial monophasic action potential (MAP) recordings were obtained from infarcted border zone (IBZ) and none infarcted zone (NIZ) of left ventricular epicardium for calculation action potential duration (APD) and activation time (AT). Immunofluorescence and immunoblots were used to determine the expression and distribution of Cx43, collagen I and Kv4.2.
Results PES showed a significant reduced VTs, raised VFT and VERP in MSCs treated rats compared to PBS treated animals. MSCs implantation led to markedly longer APD and shorter AT in IBZ than PBS treated hearts. Histological study revealed that fibrotic area and collagen deposition in infarcted region were significantly lower in MI-MSCs group than in MI-PBS group. Abnormal alterations of Cx43 including reduction and lateralisation were significantly attenuated by MSCs treatment. Inhibition of Kv4.2 expression was partly ameliorated by MSCs therapy.
Conclusions This study provide strong evidence that MSCs implantation ameliorates interstitial fibrosis and the remodelling of gap junction and Kv4.2 expression, attenuates focal heterogeneity of reporlarisation and conduction and reduces vulnerability to VTs. These results suggest that MSC transplantation might be emerge as a new preventive strategy against VAs besides improving cardiac performance in ischaemic heart disease.