An Experimental Study Of Transplantation Of Skeletal Myoblasts Transfected By VEGF Gene Combined With Left Ventricular Repair Surgery On Ischemic Congestive Heart Failure

Objective: To study the effect of combined treatment of cell transplantation (enhanced by VEGF gene transfection) and surgical left ventricular repair on ischemic congestive heart failure. Methods: Skeletal myoblasts of new born Lewis rats was isolated and cultured in vitro; then transfected with Ad.VEGF₁₆₅ and the transfection efficiency and protein expression were tested; a rat model of left ventricular repair surgery on post infarction failure hearts was created by plicating the ventricular aneurysm; 60 Lewis rats with an infarction size of about 20-40% of the left ventricle were screened out by echocardiography and randomized into five groups(12 in each group): group â…  to group â…£ received left ventricular repair surgery, then different treatments were administered concomitantly (Group â…  , transplanted with myoblasts transfected by Ad.VEGF₁₆₅; Group â…¡, transplanted with myoblasts alone; Groupâ…¢, injected with Ad.VEGF₁₆₅ alone; Groupâ…£, injected with PBS); groupâ…¤ received rethoracotomy without LV repair, then myoblasts transfected by Ad.VEGF₁₆₅ was injected directly into the border zone of the infarction area. All animals were followed 4 weeks after the second operation. Cardiac function was assessed by echocardiography and examination of hemodynamics; survival of transplantated cells, expression of VEGF protein, angiogenesis and apoptosis of myocardium were assessed by pathological examination. Results: After left ventricular repair surgery, the size of left ventricular chamber decreased significantly and LV function improved. But if no additional treatments were given, the effects deteriorated as time passes, the LV dimension and systolic function would return to the pre-operation level 4 weeks after the second surgery. Myoblasts transplantation or VEGF gene transfection were helpful to preserve the surgical results, especially when administered in a combination manner, LV chamber size and function in group I were significantly superior to others at the fourth week of the treatment(p<0.01). There were more survived myoblast cells detected in Ad.VEGF₁₆₅ transfected group; more VEGF protein expression, enhanced neovascularization and less apoptosis of myocardium were also confirmed. Conclusions: Combination of transplantation of skeletal myoblasts transfected by VEGF gene and left ventricular repair can improve the cardiac function of the ischemic congestive heart failure rats significantly. Skeletal myoblasts cultured in vitro can survive in the transplanted heart, improve the elasticity of the diseased myocardium and preserve the surgical results. Transfection of Ad.VEGF|65 can improve the survival of the transplanted cells, give rise to angiogenesis and preserve the cardiac function better.