Myoblast Sheet Can Prevent the Impairment of Cardiac Diastolic Function and Late Remodeling After Left Ventricular Restoration in Ischemic Cardiomyopathy

Abstract

Impairment of diastolic function and late remodeling are concerns after left ventricular restoration (LVR) for ischemic cardiomyopathy. This study aims to evaluate the effects of combined surgery of myoblast sheets (MS) implantation and LVR. Rat myocardial infarction model was established 2 weeks after left anterior descending artery ligation. They were divided into three groups: sham operation (n=15; group sham), LVR by plicating the infracted area (n=15; group LVR), and MS implantation with LVR (n=15; group LVR+MS). Serial echocardiographic study revealed significant LV redilatation and decrease of ejection fraction 4 weeks after LVR in group LVR. MS implantation combined with LVR prevented those later deteriorations of LV function in group LVR+MS. Four weeks after the operation, a hemodynamic assessment using a pressure-volume loop showed significantly preserved diastolic function in group LVR+MS; end-diastolic pressure (LVR vs. LVR+MS: 9.0±6.6 mm Hg vs. 2.0±1.0 mm Hg, P<0.05), end-diastolic pressure-volume relationship (LVR vs. LVR+MS 42±23 vs. 13±6, P<0.05). Histological examination revealed cellular hypertrophy and LV fibrosis were significantly less and vascular density was significantly higher in group LVR+MS than in the other two groups. Reverse transcription polymerase chain reaction demonstrated significantly suppressed expression of transforming growth factor-beta, Smad2, and reversion-inducing cysteine-rich protein with Kazal motifs in group LVR+MS. MS implantation decreased cardiac fibrosis by suppressing the profibrotic gene expression and attenuated the impairment of diastolic function and the late remodeling after LVR. It is suggesting that MS implantation may improve long-term outcome of LVR for ischemic heart disease.