Contractile dysfunction of cardiomyopathic hamster myocytes is pronounced under high load conditions
Contractile dysfunction of cardiomyopathic hamster myocytes is pronounced under high load conditions
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DOI：
10.1016/j.yjmcc.2005.03.022
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发表时间：
2005-08-01
影响因子：
5
通讯作者：
Sugiura, S
中科院分区：
文献类型：
--
作者：
Nishimura, S;Yamashita, H;Sugiura, S
为了了解遗传性心肌病的病理生理，我们在细胞水平上研究了心肌病仓鼠的收缩功能。然而，迄今为止的大多数研究都描述了在无负荷条件下细胞的缩短。利用一种新型的单个心肌细胞力长度测量系统，我们研究了心肌病仓鼠心肌细胞在大范围负荷条件下的收缩功能。从8至10周龄的心肌病（CMP）仓鼠（Bio to -2菌株）和对照（CTRL）叙利亚仓鼠的心室中分离心肌细胞。将一对碳纤维附着在单个心肌细胞的两端，通过控制纤维运动改变后负荷，记录其收缩特性。在无负荷条件下，CMP仓鼠心肌细胞的缩短率（CMP 9.2 +/- 0.5%比CTRL 10.7 +/- 0.8%, P = 0.06）和最大缩短速度（CMP 98.2 +/- 7.3 mum /s比CTRL 147.2 +/- 6.5 mum /s, P < 0.05）降低。生理负荷条件下的峰值力(CMP 35.8 +/- 2.2 mN/mm（2) vs CTRL 69.0 +/- 8.4 mN/mm(2), p < 0.05）和外功(CMP 898 +/- 130 J/m（3) vs CTRL 3058 +/- 576 J/m(3), p < 0.05）也有所降低，但在负荷条件下差异更为明显。吲哚-1测定的钙瞬变显示CMP肌细胞舒张水平升高，峰值水平降低，舒张衰减减慢，因此与观察到的收缩功能障碍一致。这些结果清楚地表明负荷条件在评估CMP仓鼠肌细胞收缩功能中的重要性，并可能为该疾病收缩功能障碍的机制提供见解。(c) 2005 Elsevier Ltd版权所有。
To understand the pathophysiology of hereditary cardiomyopathy, the contractile function of cardiomyopathic hamsters has been studied at the cellular level. However, most of the studies to date have described the cell shortening under the unloaded condition. Using a novel force-length measurement system for single cardiomyocytes, we studied the contractile function of cardiomyopathic hamster myocytes over a wide range of loading conditions. Cardiomyocytes were isolated from the ventricles of eight- to 10-week-old cardiomyopathic (CMP) hamsters (Bio TO-2 strain), as well as control (CTRL) Syrian hamsters. A pair of carbon fibers was attached to both ends of single cardiomyocytes and their contractile characteristics were recorded while changing the after-load by controlling the fiber motion. Under the unloaded condition, the shortening fraction (CMP 9.2 +/- 0.5% vs. CTRL 10.7 +/- 0.8%, P = 0.06) and maximum shortening velocity (CMP 98.2 +/- 7.3 mu m/s vs. CTRL 147.2 +/- 6.5 mu m/s, P < 0.05) were decreased in CMP hamster myocytes. The peak force under the isometric condition (CMP 35.8 +/- 2.2 mN/mm(2) vs. CTRL 69.0 +/- 8.4 mN/mm(2), p < 0.05) and external work (CMP 898 +/- 130 J/m(3) VS. CTRL 3058 +/- 576 J/m(3), p < 0.05) under physiologically loaded conditions were also decreased, but the differences were more pronounced under the loaded conditions. Calcium transients measured by Indo-1 revealed elevated diastolic level, decreased peak level, and slower diastolic decay in CMP myocytes thus being consistent with the observed contractile dysfunction. These results clearly indicate the importance of the loading conditions in evaluating the contractile function of CMP hamster myocytes, and may provide insights into the mechanism of contractile dysfunction in this disease. (c) 2005 Elsevier Ltd. All rights reserved.