Perreault C L, Bing O H, Brooks W W, Ransil B J, Morgan J P
Charles A. Dana Research Institute, Boston, Mass.
Circ Res. 1990 Sep;67(3):707-12. doi: 10.1161/01.res.67.3.707.
We studied calcium responsiveness of skinned muscle preparations from the right and left ventricles of rats with cardiac hypertrophy and cardiac hypertrophy plus failure. To test the hypothesis that differences in contractile function are due to changes in myofilament calcium responsiveness, we compared preparations from spontaneously hypertensive rats with cardiac failure, spontaneously hypertensive rats without cardiac failure, and age-matched normotensive Wistar-Kyoto control rats 18-24 months of age. Rats with failure had pleural/pericardial effusions, left atrial thrombi, and right and left ventricular hypertrophy. Muscles were skinned by saponin (250 micrograms/ml) and activated with a series of calcium buffers. Data were plotted as pCa (-log[Ca2+]) versus isometric force and then fit to a modified Hill equation. Values for 50% maximal activation (calcium sensitivity), maximal calcium-activated force, and the slope of the calcium-force relation were compared. Our data indicate that with the development of hypertrophy, calcium sensitivity of left ventricular muscles remains unaffected, but maximal calcium-activated force is increased. In contrast, maximal calcium-activated force declines toward control levels with the development of left ventricular failure, despite the continued presence of significant hypertrophy. In the normotensive rats, the left ventricle is more sensitive to calcium than the right ventricle (pCa50 = 6.0 +/- 0.05 versus 5.7 +/- 0.09; p less than 0.05); however, both the calcium sensitivity and maximal calcium-activated force of the right ventricle increase with the development of compensatory hypertrophy secondary to left ventricular failure. These changes that occur in rats with cardiac hypertrophy and failure may represent important physiological adaptive mechanisms.
我们研究了患有心肌肥厚以及心肌肥厚伴心力衰竭的大鼠左右心室的去表皮肌肉制剂的钙反应性。为了验证收缩功能差异是由于肌丝钙反应性变化这一假设，我们比较了来自患有心力衰竭的自发性高血压大鼠、无心力衰竭的自发性高血压大鼠以及年龄匹配的18 - 24月龄正常血压Wistar - Kyoto对照大鼠的制剂。患有心力衰竭的大鼠有胸腔/心包积液、左心房血栓以及左右心室肥厚。肌肉用皂角苷（250微克/毫升）去表皮，并用一系列钙缓冲液激活。数据绘制成pCa（-log[Ca2 +]）对等长力的曲线，然后拟合到修正的希尔方程。比较了50%最大激活值（钙敏感性）、最大钙激活力以及钙 - 力关系的斜率。我们的数据表明，随着肥厚的发展，左心室肌肉的钙敏感性保持不变，但最大钙激活力增加。相比之下，尽管左心室持续存在显著肥厚，但随着左心室衰竭的发展，最大钙激活力下降至对照水平。在正常血压大鼠中，左心室对钙比右心室更敏感（pCa50 = 6.0±0.05对5.7±0.09；p < 0.05）；然而，继发于左心室衰竭的代偿性肥厚发展过程中，右心室的钙敏感性和最大钙激活力均增加。心肌肥厚和衰竭大鼠中发生的这些变化可能代表重要的生理适应性机制。
