The value of intrapericardial injection with a trans-diaphragmatic approach in the gene therapy of chronic heart failure rats

AIM: To study the feasibility, security and validity of the intrapericardial injection with a trans-diaphragmatic approach in chronic heart failure rats and its value in the study of gene therapy for heart diseases, and further investigate whether adeno-associated virual gene transfer of sarcoplasmic reticulum Ca2+-ATPase （SERCA2a） gene can improve ventricular function in chronic heart failure (HF) rats. METHODS: An animal model of heart failure was obtained by creating descending aortic constriction in rats. Recombinant adeno-associated virus, carrying enhanced green fluorescent protein (EGFP) gene and recombinant adeno-associated virus carrying SERCA2a gene, were respectively injected into pericardium of heart failure rats in different groups (group HF+EGFP and group HF+SERCA2a) by intrapericardial injection with a trans-diaphragmatic approach. After 30 days, hemodynamic parameters were measured and analyzed. Cryosection was analyzed by fluorescence microscopy to examine the expression of green fluorescent protein, and Western blotting was performed to detect the expression of SERCA2a. RESULTS: Green fluorescence was detected in cryosection of the hearts in all rats in group HF+EGFP and the expression of green fluorescent protein was ubiquitously. The expression of SERCA2a in all rats in group HF+SERCA2a was more than those in group HF and group HF+EGFP. And overexpression of SERCA2a improved the systolic and diastolic function of heart failure rats significantly and the hemodynamic parameters were similar with those of the controls. CONCLUSION: The intrapericardial injection with a trans-diaphragmatic approach suggests a simple, safe, efficient and cheap technique for the gene therapy of chronic heart failure. Gene thransfer of SERCA2a may be a new approach for the treatment of chronic heart failure.