Hoashi Takaya, Matsumiya Goro, Miyagawa Shigeru, Ichikawa Hajime, Ueno Takayoshi, Ono Masamichi, Saito Atsuhiro, Shimizu Tatsuya, Okano Teruo, Kawaguchi Naomasa, Matsuura Nariaki, Sawa Yoshiki
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
J Thorac Cardiovasc Surg. 2009 Aug;138(2):460-7. doi: 10.1016/j.jtcvs.2009.02.018.
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.
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).
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.
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.
右心室功能障碍已成为复杂先天性心脏病手术修复后的常见问题。最近一项研究报告称，组织工程化骨骼肌成肌细胞片移植可改善扩张型和缺血性心肌病患者的左心室功能。因此，成肌细胞片移植可能也会改善压力负荷过重右心室大鼠模型的心室功能。
7周龄雄性Lewis大鼠接受肺动脉环扎术。肺动脉环扎术后4周，成肌细胞片移植组（n = 20）将成肌细胞片移植到右心室，而假手术组（n = 20）进行假手术。
手术后4周，通过压力-容积环进行的血流动力学评估显示两组的收缩功能均有代偿性增加。然而，只有成肌细胞片移植组的舒张功能有显著改善：舒张末期压力（假手术组与成肌细胞片移植组，10.3±3.1 vs 5.0±3.7 mmHg；P <.001）、等容舒张时间常数（11.1±2.5 vs 7.6±1.2 ms，P <.001）和舒张末期压力-容积关系（16.1±4.5 vs 7.6±2.4/mL，P <.005）。两组的右心室重量和细胞大小同样增加。组织学评估显示，与假手术组相比，成肌细胞片移植组的心室纤维化明显受到抑制，毛细血管密度增加。逆转录-聚合酶链反应显示，成肌细胞片移植组心肌中肝细胞生长因子和血管内皮生长因子的基因表达增加，而假手术组未增加。
在压力负荷过重右心室大鼠模型中，骨骼肌成肌细胞片移植改善了舒张功能障碍，抑制了心室纤维化，并增加了毛细血管密度。该方法可能成为先天性心脏病患者右心室衰竭心肌再生的新策略。
