LAUSR

Objective: We aimed to investigate the possibility of combining BMSCs transplantation (BMSCs T) with sarcoplasmic reticulum Ca2+ATase (SERCA2a) and connexins 43 (Cx43) genes transfection mediated by ultrasound-targeted microbubble destruction (UTMD) to treat heart failure (HF) and ventricular arrhythmia (VA) after MI. Methods: HF rats received BMSCs T 4 weeks after AMI. Two days later, microbubbles carried SERCA2a and Cx43 genes were injected via tail vein, then ruptured by irradiation. 63 rats were divided into 7 groups : 1)SHAM; 2)HF; 3)UTMD; 4)BMSCs + UTMD; 5)BMSCs + UTMD-SERCA2a; 6)BMSCs + UTMD-Cx43; 7)BMSCs+ UTMD-SERCA2a/Cx43-1:1. Left ventricular ejection fraction (LVEF), cardiac tolerance to electrical stimulation were examined 28 days after BMSCs T. Results: The LVEF of gene transfection groups were improved than before: BMSCs + UTMD-SERCA2a (39.6±3.6% vs. 34.3±4.3%); BMSCs + UTMD-Cx43 (40.1±5.6% vs. 35.1±5.2%); BMSCs + UTMD-SERCA2a/Cx43-1:1 (41.7±6.8% vs. 35.1±5.2%) (P < 0.05). Stimulating with 7V voltage, the frequencies of inducing VA in BMSCs + UTMD-SERCA2a, BMSCs + UTMD-Cx43 and BMSCs + UTMD-SERCA2a/Cx43-1:1 were 13.07±4.77Hz, 13.94±1.29Hz and 13.97±1.91Hz, which were higher than HF and non-gene groups (P < 0.05). With 8V, the frequencies in BMSCs + UTMD-Cx43 and BMSCs+ UTMD-SERCA2a/Cx43-1:1 were also higher than other groups but SHAM (P < 0.05). The frequency of double-gene group was higher than single-gene groups with 8V (P < 0.05). Conclusion: Our results suggest that BMSCs T assisted by UTMD-mediated SERCA2a and Cx43 genes transfection can improve HF and VA after MI, and especially for the stability of cardiac electrical activity with double-gene.