Abstract 13717: Autologous Skeletal Myoblast Patch Remodeled Swine Pressure-overloaded Right Heart by Amelioration in Myocardial Ischemia

Abstract

Introduction: Myocardial ischemia (MI) is majorly seen in the right ventricular (RV) dysfunction in patients with congenital heart disease secondary to residual hemodynamic stressors in form of pressure-overloaded, suggesting therapeutic target for RV dysfunction may be how to control MI. Autologous skeletal myoblast patch showed the angiogenetic effect for left ventricular dysfunction by cytokine paracrine effects, which are expected to be sufficiently effective against pressure-overloaded RV dysfunction. Hypothesis: An autologous skeletal myoblast patch alleviates the MI in a pressure-overloaded right heart in swine model, leading to amelioration of metabolic and functional dysfunction. Methods: Five-month-old mini-pigs underwent pulmonary artery banding. Two months after banding, myoblast patch derived from autologous skeletal muscles were placed on the epicardium of RV free wall. Groups were as follows: control (C, n=6), sheet implantation (S, n=6). Two months after sheet implantation, cardiac function exam and C11-Acetate positron emission tomography (PET) were done, and hearts were dissected for histologic and real-time polymerase chain reaction (RT-PCR) analysis. Results: Two months after sheet implantation, RV dysfunction was significantly ameliorated in group S than group C (RVEF; S 44.9+/-2.2 vs C 31.9+/-2.1 % [p=0.0042]). PET revealed the deterioration of myocardial blood flow (Rest/Stress; S 3.22+/-0.39 vs C 2.13+/-0.92 min -1 [p=0.0421]) and myocardial oxidative metabolism (K mono -Rest/Stress: S 3.17+/-0.69 vs C 2.03+/-0.65 min -1 [p=0.0421]) were suppressed in group S than group C. In histologic analysis, group S presented more angiogenesis in CD31 expression (S 18.3+/-1.5 vs C 10.7+/-2.8 units/cells [p=0.0122]). In RT-PCR analysis, mRNA expression of vascular endothelial growth factor (S 1.28+/-0.35 vs C 0.75+/-0.17 folds [p=0.030]), hepatocyte growth factor (S 1.70+/-0.79 vs C 0.74+/-0.10 folds [p=0.030]), and chemokine stromal cell-derived factor-1 (S 1.49+/-0.97 vs C 0.35+/-0.20 folds [p=0.030]) were upregulated in group S than group C. Conclusions: Autologous skeletal myoblast patch ameliorated metabolic and functional dysfunction in a swine model of pressure-overloaded right heart by alleviation of MI.