Calcium sensitivity of isometric tension is increased in canine experimental heart failure.
Calcium sensitivity of isometric tension is increased in canine experimental heart failure.
复制标题
犬实验性心力衰竭中等长张力的钙敏感性增加。
DOI：
10.1161/01.res.76.5.781
复制
发表时间：
1995
影响因子：
20.1
通讯作者：
Moss,RL
中科院分区：
文献类型：
--
作者：
Wolff,MR;Whitesell,LF;Moss,RL
为了研究慢性心力衰竭中肌纤维功能改变的作用，我们从慢性快速起搏引起的扩张型心肌病（DCM）犬模型中测定了渗透性心肌的等长张力- pca关系。在最初的一系列实验中，7只狗以每分钟250次的节奏持续28.9±7.0天，导致超声心动图显示心室扩张，射血分数降低，心内充盈压力升高。在慢性快速起搏引起的心力衰竭之前（n=11）和之后（n=10），使用左心室活检获得的机械破坏和渗透性心肌细胞大小的制剂来测量等长张力与pca的关系。静息肌节长度（SL）设定为2.35 μm，制剂的顺应性较低（最大激活时SL为2.23±0.03 μm）。被动张力（2.1±1.0 vs 2.4±0.6 mN/mm2）和最大Ca2+激活张力（25.9±9.3 vs 27.8±6.8 mN/mm2）在对照和DCM制剂中分别相似。而衰竭心肌等径张力钙敏感性升高（pCa505.95±0.11 [DCM] vs . 5.83±0.10[对照]，P=.001）。用蛋白激酶A的催化亚基处理肌原纤维制剂，失败制剂（pca50从6.04±0.06变为5.75±0.09,n=7）比未失败制剂（5.91±0.08变为5.74±0.07,n=8）更大程度地降低了钙对张力的敏感性，两组在蛋白激酶A处理后的等长张力- pca关系无显著差异。这些数据表明，DCM中钙敏感性的增加可能至少部分是由于肾上腺素能介导的肌纤维调节蛋白磷酸化的减少。等长张力增加的钙敏感性可能部分补偿DCM中收缩钙瞬变的减少，但也可能导致伴随此病的舒张功能障碍。
To examine the role of alterations in myofibrillar function in chronic heart failure, we determined isometric tension–pCa relations in permeabilized myocardium from a canine model of dilated cardiomyopathy (DCM) produced by chronic rapid pacing. In the initial series of experiments, seven dogs were paced at 250 beats per minute for 28.9±7.0 days, resulting in ventricular dilatation and reduced ejection fractions by echocardiography and elevated intracardiac filling pressures. Isometric tension–pCa relations were measured by using mechanically disrupted and permeabilized myocyte-sized preparations obtained from left ventricular biopsies before (n=11) and after (n=10) chronic rapid pacing–induced heart failure. Resting sarcomere length (SL) was set at 2.35 μm, and preparations had low end compliance (SL was 2.23±0.03 μm during maximal activation). Passive tension (2.1±1.0 versus 2.4±0.6 mN/mm2) and maximal Ca2+-activated tension (25.9±9.3 versus 27.8±6.8 mN/mm2) were similar for control and DCM preparations, respectively. However, the calcium sensitivity of isometric tension was increased in failing myocardium (pCa505.95±0.11 [DCM] versus 5.83±0.10 [control],P=.001). Treatment of myofibrillar preparations with the catalytic subunit of protein kinase A decreased calcium sensitivity of tension to a greater degree in failing preparations (shift of pCa50from 6.04±0.06 to 5.75±0.09, n=7) than in nonfailing preparations (5.91±0.08 to 5.74±0.07, n=8), and isometric tension–pCa relations in the two groups were not significantly different after protein kinase A treatment. These data suggest that the increased calcium sensitivity in DCM may be due at least in part to a reduction of the adrenergically mediated phosphorylation of myofibrillar regulatory proteins. This increased calcium sensitivity of isometric tension may partially compensate for decreases in systolic calcium transients in DCM but may also contribute to the diastolic dysfunction that accompanies this condition.