Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart
Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart
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DOI：
10.1016/j.jtcvs.2009.02.018
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发表时间：
2009-08-01
影响因子：
6
通讯作者：
Sawa, Yoshiki
中科院分区：
文献类型：
--
作者：
Hoashi, Takaya;Matsumiya, Goro;Sawa, Yoshiki
目的：复杂先天性心脏病（先心病）手术后右心功能不全的发生已成为一个常见问题。最近的一项研究报告称，组织工程化骨骼成肌细胞片移植可改善扩张性和缺血性心肌病患者的左心室功能。因此，成肌细胞片移植也可能改善大鼠模型的压力负荷过重的右ventricular.Methods：七周龄雄性刘易斯大鼠进行肺动脉结扎的心室性能。肺动脉结扎术后4周，成肌细胞片移植组（n = 20）行成肌细胞片移植至右心室，假手术组（n = 20）行假手术。结果：术后4周，两组大鼠的血流动力学均显示收缩功能代偿性增强。然而，只有成肌细胞片移植组显示舒张功能显著改善：舒张末期压（假手术组与成肌细胞片移植组，10.3 ± 3.1 vs 5.0 ± 3.7 mm Hg;等容舒张时间常数（11.1 +/- 2.5 vs 7.6 +/- 1.2 ms，P <0.001）和舒张末期压力-容积关系（16.1 +/- 4.5 vs 7.6 +/- 2.4/mL，P <0.005）。两组的右心室重量和细胞大小相似地增加。组织学评估表明，与假手术组相比，成肌细胞片移植组的心室纤维化明显抑制，毛细血管密度增加。逆转录-聚合酶链反应显示，心肌基因表达的肝细胞生长因子和血管内皮生长因子在成肌细胞片移植组，但不是在sham group.Conclusions：Skeleton成肌细胞片移植改善舒张功能障碍和抑制心室纤维化与增加毛细血管密度在大鼠模型的压力超负荷右心室。该方法有望成为先天性心脏病右心室衰竭心肌再生的新策略。
Objective: The development of right ventricular dysfunction has become a common problem after surgical repair of complex congenital heart disease. A recent study reported that tissue-engineered skeletal myoblast sheet transplantation improves left ventricular function in patients with dilated and ischemic cardiomyopathy. Therefore myoblast sheet transplantation might also improve ventricular performance in a rat model of a pressure-overloaded right ventricle.Methods: Seven-week-old male Lewis rats underwent pulmonary artery banding. Four weeks after pulmonary artery banding, myoblast sheet transplantation to the right ventricle was performed in the myoblast sheet transplantation group (n = 20), whereas a sham operation was performed in the sham group (n = 20).Results: Four weeks after performing the procedure, a hemodynamic assessment with a pressure-volume loop showed a compensatory increase in systolic function in both groups. However, only the myoblast sheet transplantation group showed a significant improvement in the diastolic function: end-diastolic pressure (sham vs myoblast sheet transplantation, 10.3 +/- 3.1 vs 5.0 +/- 3.7 mm Hg; P < .001), time constant of isovolumic relaxation (11.1 +/- 2.5 vs 7.6 +/- 1.2 ms, P < .001), and end-diastolic pressure-volume relationship (16.1 +/- 4.5 vs 7.6 +/- 2.4/mL, P < .005). The right ventricular weight and cell size similarly increased in both groups. A histologic assessment demonstrated significantly suppressed ventricular fibrosis and increased capillary density in the myoblast sheet transplantation group in comparison with those in the sham group. Reverse transcription-polymerase chain reaction demonstrated an increased myocardial gene expression of hepatocyte growth factor and vascular endothelial growth factor in the myoblast sheet transplantation group but not in the sham group.Conclusions: Skeletal myoblast sheet transplantation improved the diastolic dysfunction and suppressed ventricular fibrosis with increased capillary density in a rat model of a pressure-overloaded right ventricle. This method might become a novel strategy for the myocardial regeneration of right ventricular failure in patients with congenital heart disease.