Abstract 3130: Skeletal Myoblast Sheet Transplantation Suppressed Endocardial Fibrosis And Improved Diastolic Function In Pressure-induced Right Heart Failure: A Strategy Of Myocardial Regeneration In Congenital Heart Disease
Background: Development of right ventricular dysfunction by pressure overload is often seen even after definitive repair for congenital heart defects. After a compensated hypertrophy period, prolonged exposure to the excess pressure overload finally results in an irreversible RV failure. Recently, tissue-engineered skeletal myoblast sheet (MS) transplantation is reported to improve the left ventricular function in dilated and ischemic cardiomyopathy. We investigated whether this regeneration therapy could also be applied to improve the RV function deteriorated by pressure overload.
Methods: Pulmonary arterial banding (PAB) was performed in seven-week-old male Lewis rats. MSs were created using temperature-responsive culture dishes. Four weeks after PAB, MSs grafting onto the anterior wall of RV was performed in MS group, or sham operation in sham group. The measurement of hemodynamic assessment using pressure and conductance catheters for RV pressure-volume loop (PV loop) analysis, the fibrosis using Masson Trichrome stain and the plasma brain natriuretic peptide (pBNP) level were performed 4 weeks after the procedure.
Results: PV loop analysis showed a compensatory increase in systolic function in both group. However, end-diastolic pressure volume relationship (EDPVR) and time constant of isovolumic relaxation (τ) were increased in sham group, whereas these indices remain unchanged in MS group. (EDPVR: 56.9 ± 20.9 versus 25.1 ± 7.9 mmHg/ml; P<.002, τ: 11.7 ± 2.2 versus 7.6 ± 1.2 msec; P<.001). Interstitial fibrosis was suppressed in MS group (4.0 ± 1.1 versus 3.0 ± 0.9 %; P<.01). Furthermore, aggregated subendocardial myocardial fibrosis, which was confirmed in PAB group, was not detected in MS group. The pBNP level remained lower in MS group than in PAB group (175.6 ± 47.2 versus 230.0 ± 49.0 pg/ml; P<.03).
Conclusions: Impairment of right ventricular diastolic function after chronic pressure overload was revealed by the pressure-volume loop analysis. Skeletal myoblast sheet transplantation attenuated the diastolic dysfunction, which is supposed to be caused by suppressed myocardial fibrosis. Therefore, this method may promise a strategy of myocardial regeneration for right ventricle failure in congenital heart disease patients.