Abstract 13020: Evidence of Improvement in Diastolic Cardiac Function by Cell-Sheet Therapy in a Canine Dilated Cardiomyopathy Model
Background: Diastolic function in the left ventricle (LV) has been proved to be critical in determining prognosis of cardiac failure. On the other hand, cell transplantation therapy for chronic cardiac failure has been shown to be symptomatically effective in clinical studies, despite modest improvement in systolic function. We hypothesized that cell transplantation may ameliorate systolic and diastolic LV function in dilated cardiomyopathy (DCM).
Methods: A DCM model was generated by rapid-ventricular pacing for 4 weeks in 11 beagles. Subsequently, the canines underwent transplantation of autologous skeletal myoblast cell-sheet (SMCST) onto the lateral LV wall (SMCST group, n=6), or sham operation (sham group, n=5) with further continuation of rapid-pacing for 4 weeks. Global systolic and diastolic LV function was evaluated by standard echocardiography and catheter study, while regional function and ventricular dyssynchrony were assessed by speckle-tracking echocardiography.
Results: Ejection fraction and end-systolic elastance was significantly greater in the SMCST group (47±3% and 8±1 mmHg/ml, respectively) than the control group (20±2% and 3±1 mmHg/ml, respectively). In addition, E/E`, isovolumetric relaxation time and tau were significantly smaller in the SMCST group (11±0.4, 76±3 msec and 34±2 msec, respectively) than the control group (16±0.5, 99±2 msec and 48±4 msec, respectively). Speckle-tracking echocardiography revealed that regional systolic and diastolic function as well as LV dyssynchrony in both septal and lateral area significantly improved in the SMCST group than the control group. Amount of interstitial fibrosis was significantly smaller in both septal and lateral areas of the SMCST group (%fibrosis; septal, 11.3±0.5 %, lateral, 10.1±0.5 %, respectively) than the control group (24.0±0.3 %, 23.7±0.5 %, respectively, p <0.001).
Conclusion: SMCST improved systolic and diastolic function and attenuated LV dyssynchrony in canine DCM model, warranting assessment of diastolic function or regional function to measure the therapeutic effects of cell transplantation in clinical study.
- © 2012 by American Heart Association, Inc.