CELL GEOMETRY AND CONTRACTILE ABNORMALITIES OF MYOCYTES FROM FAILING HUMAN LEFT-VENTRICLE
CELL GEOMETRY AND CONTRACTILE ABNORMALITIES OF MYOCYTES FROM FAILING HUMAN LEFT-VENTRICLE
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DOI：
10.1016/0008-6363(95)00040-2
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发表时间：
1995-08-01
影响因子：
10.8
通讯作者：
HARDING, SE
中科院分区：
文献类型：
--
作者：
DELMONTE, F;OGARA, P;HARDING, SE
目的：衰竭的人类心脏的收缩和舒张功能障碍可能是由于肌细胞功能的变化，或由于细胞外的影响，如坏死、纤维化或活细胞的重新定位。为了确定细胞因子的贡献，我们已经表征了从衰竭的人左心室分离的单个肌细胞的收缩幅度、收缩和舒张速度。方法：从42名受试者的左心室酶法分离心肌细胞，在32 ℃下灌流，以0.2 Hz起搏。使用视频/边缘跟踪系统，我们获得了收缩幅度和收缩和松弛速度以及达到峰值收缩的时间（TTP）和达到50%和90%松弛的时间（R50和R90）。构建了每个细胞对Ca 2+的浓度-响应曲线。结果如下：在这种低频率下，在任何Ca 2+浓度下，衰竭和非衰竭心脏的细胞之间的收缩幅度几乎没有差异。在最大激活Ca 2+浓度（6-20 mM）下，轻度-中度（P < 0.001）和重度（P <0.001）充血性心力衰竭患者的心肌细胞舒张速度减慢30%。心力衰竭心肌细胞的收缩和舒张时间增加[TTP：0.46 +/- 0.02 s（n = 34名患者）对比0.35 +/- 0.02 s（n = 6），P < 0.01和R50：0.25 +/- 0.02 s（n = 34）对比0.16 +/- 0.02 s（n = 6），P < 0.001]。在大多数病因中观察到舒张受损，包括缺血性和扩张性心肌病和二尖瓣疾病。心肌细胞从失败的肥厚的心室受到更严重的影响比那些从失败的非肥厚的心脏收缩和舒张速度。尽管两组间细胞长度和肌节长度相似，但来自衰竭肥厚心室的细胞的面积显著大于来自非衰竭或衰竭非肥厚心室的细胞。较大的心肌细胞并没有表现出更明显的变化，在松弛速度比正常大小的细胞从同一肥厚的心室。结论：在收缩幅度正常的条件下，在衰竭的人心脏的心室肌细胞中可以观察到显著的舒张受损。该缺陷并不局限于一种病因的疾病，但在肥大过程中加剧。虽然在肥大心室的肌细胞中观察到细胞大小的增加，但其本身并不能解释舒张的变化。细胞的变化会导致衰竭的人类心脏的舒张功能障碍。
Objectives: Systolic and diastolic dysfunction of the failing human heart may be due to changes in myocyte function, or to extracellular influences such as necrosis, fibrosis or repositioning of viable cells. In order to determine the contribution of cellular factors we have characterised the contraction amplitudes, and contraction and relaxation velocities of single myocytes isolated from failing human left ventricle. Methods: Myocytes were enzymatically isolated from the left ventricles of 42 subjects, superfused at 32 degrees C and paced at 0.2 Hz. Using a video/edge tracking system we obtained contraction amplitude and contraction and relaxation velocities as well as times to peak contraction (TTP) and to 50% and 90% relaxation (R50 and R90). Concentration-response curves to Ca2+ were constructed for each cell. Results: There was little difference in contraction amplitude at any Ca2+ concentration between cells from failing and non-failing hearts at this low frequency. At maximally activating Ca2+ concentrations (6-20 mM) there was a 30% slowing of relaxation velocity in myocytes from patients with both mild-moderate (P < 0.001) and severe (P < 0.001) congestive heart failure. Contraction and relaxation times were increased in myocytes from failing hearts [TTP: 0.46 +/- 0.02 s (n = 34 patients) vs. 0.35 +/- 0.02 s (n = 6), P < 0.01 and R50: 0.25 +/- 0.02 s (n = 34) vs. 0.16 +/- 0.02 s (n = 6), P < 0.001]. Impaired relaxation was seen with most etiologies, including ischemic and dilated cardiomyopathies and mitral valve disease. Myocytes from failing hypertrophied ventricles were more severely affected than those from failing non-hypertrophied hearts for both contraction and relaxation velocities. Cells from failing hypertrophied ventricles had a significantly larger area than from non-failing or failing non-hypertrophied ventricles, although cell length and sarcomere length were similar between groups. Larger myocytes did not show a more pronounced change in relaxation velocity than normally sized cells from the same hypertrophied ventricle. Conclusions: Significant impairment of relaxation can be observed in ventricular myocytes from failing human heart under conditions where contraction amplitude appears normal. The defect is not confined to one etiology of disease, but is exacerbated during hypertrophy. An increase in cell size, although observed in myocytes from hypertrophied ventricle, does not itself account for changes in relaxation. Cellular changes contribute to diastolic dysfunction in the failing human heart.