Autologous Skeletal Myoblast Transplantation Improved Left Ventricular Function In Chronic Heart Failure Dogs

Aim: In present study, we tested the effects of ASMT on hemodynamics, LV function and remodeling in coronary microembolization-induced CHF in conscious dogs. Method: â‘  Induction of CHF model: 32 dogs were included. Each dog underwent baseline assessment in a conscious state. CHF (20% to 25% reduction in dP/dt_max and LV end-diastolic pressure >14 mm Hg) was created by weekly coronary microembolizations via a coronary catheter. Finally, CHF were successfully induced in 19 dogs. â‘¡ Culture of autologous skeletal myoblast: skeletal muscle biopsy was performed under anaesthesia and myoblasts were isolated and expanded in vitro.â‘¢. Autologous skeletal myoblast transplantation: 19 dogs were put into 2 groups (ASMT group 9, control group 10). Then 4.5×10⁸ to 5.8 x 10 myoblasts were injected into the embolismed region of 9 dogs after establishment of CHF. Saline injection (sham) was performed in 10 control dogs. Animals were evaluated after 4-6weeks. Global ejection fraction was determined by echocardiography. The levels of neurohormone were tested by radioimmunity and HPLC-ECD. Results: â‘ CHF were successfully induced in 19 dogs. Other dogs died of severe infection, ventricular fibrillation, over- anaesthesia and severe heart failure. â‘¡ Compared with the base line, the levels of norepinephrine (NE), angiotonin II (AgII), endothelin-1 (ET-1), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were significantly increased in 19 CHF dogs (P<0.01). EF, dP/dtmax ,mean arterial pressure (MAP) (P<0.01) , and left ventricular systolic pressure (LVSP) were markedly decreased. End-systolic area (ESA), end-diastolic area (EDA) and LVEDP all increased (P<0.01); heart rate (HR) had no changes (P>0.05 ). â‘¢ Compared with saline injection, ASMT significantly increased dP/dtmax MAP, LVSP and EF (P<0.01), in the same time,significantly decreased NE, AgII, ET-1, ANP, BNP, ESA, EDA, and LVEDP (P<0.01) at 4-6weeks after myoblast transplantation. â‘£By desmin and Brd-U immunofluorescent staining, myoblast was proved survived in injucted site. Compared with saline injection, ASMT significantly lessened the injury of myocardium. Conclusion: â‘  Stable CHF can be created by weekly coronary microembolizations via a coronary catheter, which is similar to the human' CHF in the manifestation and pathogenesis. â‘¡ Autologous skeletal myoblast can survive in injucted site. â‘¢ASMT provided mild improvements in hemodynamics and LV function and reduced LV remodeling in conscious dogs with CHF.