Mesenchymal stem cell injection ameliorates the inducibility of ventricular arrhythmias after myocardial infarction in rats

Background: Mesenchymal stem cell transplantation is a promising new therapy to improve cardiac function after myocardial infarction (MI). The electrophysiological consequences of MSC implantation has not been systematically studied. Methods: We investigated the electrophysiological and arrhythmogenic effects of mesenchymal stem cells (MSCs) therapy in experimental infarction model. Rats were subjected to MI operation by LAD ligation and randomly allocated to receive intramyocardially injection PBS (MI-PBS) or 5x10(5) EGFP labeled MSCs (MI-MSCs). Electrophysiological study, histological examination, and western blotting were performed 2 weeks after cell transplantation. Results: Programmed electrical stimulation (PES) showed a significant reduced inducible ventricular tachycardias (VTs), raised ventricular fibrillation threshold (VFT) and prolonged ventricular effective refractory period (VERP) in MSC-treated rats compared to PBS-treated animals. MSC implantation led to markedly longer action potential duration (APD) and shorter activation time (AT) in infarcted border zone (IBZ) of left ventricular epicardium compared with PBS-treated hearts. Histological study revealed that fibrotic area and collagen deposition in infarcted region were significantly lower in MI-MSC group than in MI-PBS group. Abnormal alterations of Connexin 43 including reduction and lateralization were significantly attenuated by MSC treatment. Conclusions: This study provide strong evidence that MSC implantation ameliorates interstitial fibrosis and the remodeling of gap junction, attenuates focal heterogeneity of reporlarization and conduction and reduces vulnerability to VTs. The results suggest that MSC transplantation might emerge as a new preventive strategy against VAs besides improving cardiac performance in ischemic heart disease. (C) 2010 Elsevier Ireland Ltd. All rights reserved.