BACKGROUND: The impact of autologous skeletal myoblasts (ASM) on cardiac function and geometry has not been defined in animals with dilated ischemic heart failure (HF). METHODS: HF (LVEF < 35%, LVESVI > 80ml/m²) was created in sheep via coronary microembolizations. After instrumentation/HF induction, five sheep underwent ASM injection (3.0x10^8 cells) (n=5, ASM), while six others were used as controls (n=6, Control). Hemodynamic variables, cardiac geometry (sonomicrometry) and pressure-volume relationships (IVC occluder) were studied weekly in all animals for 6 weeks, and analyzed using a two-way (time-group) ANOVA (p<0.05).
RESULTS: At week 6, differentiated myoblasts (aligned and in close apposition with remaining myocytes) were found in all ASM sheep. However, ASM fibers did not stain for connexin43, and no functional parameter studied (LVEF, ESPVR, PRSW or LV segment shortening), was significantly improved versus control animals. In ASM animals, LV dilatation at week 6 (14±7 %wk.1) was attenuated versus controls (31±16 %wk.1). Furthermore, attenuation was limited to the short-axis and correlated with ASM survival at week 6 (see Figure, where "ASM-high" and "ASM-low" represent ~6% (n=2) and ~1% (n=3) survival, respectively).
CONCLUSIONS: In severe dilated ischemic HF, ASM transplantation significantly attenuated LV short-axis dilatation, despite a lack of significant (vs. control) improvement in cardiac function. Thus, effects on cardiac remodeling and function after ASM transplantation may be independent of each other.

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