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

Saito, Shunsuke1; Miyagawa, Shigeru1; Sakaguchi, Taichi1; Imanishi, Yukiko1; Iseoka, Hiroko1; Nishi, Hiroyuki1; Yoshikawa, Yasushi1; Fukushima, Satsuki1; Saito, Atsuhiro1; Shimizu, Tatsuya2; Okano, Teruo2; Sawa, Yoshiki1,3

doi: 10.1097/TP.0b013e31824fd803
Basic and Experimental Research

Background 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.

Methods 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).

Results 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.

Conclusions 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.

1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

2 Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan.

The authors declare no funding or conflicts of interest.

3 Address correspondence to: Yoshiki Sawa, M.D., Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine (E1), 2-2 Yamada-Oka, Suita, Osaka 565-0871, Japan.

E-mail: sawa@surg1.med.osaka-u.ac.jp

S.S. participated in research design, the performance of the research, data analysis, and the writing of the manuscript; T.S. participated in research design and data analysis; S.M. participated in research design and data analysis, and the writing of the manuscript; Y.I. performed quantitative analysis of engrafted myoblasts survival; H.I. performed histological analysis of engrafted myoblasts survival; H.N. participated in the performance of the research; Y.Y. participated in the performance of the research; S.F. participated in the performance of the research; A.S. participated in research design and data analysis; T.S. contributed to the development of the temperature-responsive culture dish and cell sheet implantation technique; T.O. contributed to the development of the temperature-responsive culture dish and cell sheet implantation technique; and Y.S. participated in research design, data analysis, and the writing of themanuscript.

Received 28 June 2011. Revision requested 20 July 2011.

Accepted 10 February 2012.

© 2012 Lippincott Williams & Wilkins, Inc.