Hajjar R J, Gwathmey J K
Medical Services, Massachusetts General Hospital, Boston.
Circulation. 1992 Dec;86(6):1819-26. doi: 10.1161/01.cir.86.6.1819.
To investigate whether altered cross-bridge kinetics contribute to the contractile abnormalities observed in heart failure, we determined the mechanical properties of cardiac muscles from control and myopathic hearts.
Muscle fibers from normal (n = 5) and dilated cardiomyopathy (n = 6) hearts were obtained and chemically skinned with saponin. The muscles were then maximally activated at saturating calcium concentrations. Unloaded shortening velocities (V0) were determined in both groups. V0 in control was 0.72 +/- 0.09 Lmax/sec, whereas in myopathic muscles, V0 was 0.41 +/- 0.06 Lmax/sec at 22 degrees C. The muscles were also sinusoidally oscillated at frequencies ranging between 0.01 and 100 Hz. The dynamic stiffness of the muscles was calculated from the ratio of force response amplitude to length oscillation amplitude. At low frequencies (< 0.2 Hz) the stiffness was constant but was larger in myopathic muscles. In the range of 0.2-1 Hz, there was a drop in the magnitude of dynamic stiffness to approximately one quarter of the low-frequency baseline. This range reflects cross-bridge turnover kinetics. In control muscles, the frequency of minimum stiffness was 0.78 +/- 0.06 Hz, whereas it was 0.42 +/- 0.07 Hz in myopathic muscles. At higher frequencies, the dynamic stiffness increased and reached a plateau at 30 Hz. There were no differences in the plateau reached between control and myopathic muscles.
Because myopathic hearts have a markedly diminished energy reserve, the slowing of the cross-bridge cycling rate plays an important adaptational role in the observed contractility changes in human heart failure. Although the potential to generate maximal Ca(2+)-activated force is similar in normal and myopathic hearts, alterations in contractile protein composition could explain the diminished cross-bridge cycling rate in failing hearts.
为研究横桥动力学改变是否导致心力衰竭时观察到的收缩异常，我们测定了对照心脏和病变心脏心肌的力学特性。
获取正常（n = 5）和扩张型心肌病（n = 6）心脏的肌纤维，用皂角苷进行化学去膜处理。然后在饱和钙浓度下使肌肉最大程度激活。测定两组肌肉的无负荷缩短速度（V0）。在22℃时，对照组的V0为0.72±0.09 Lmax/秒，而病变肌肉的V0为0.41±0.06 Lmax/秒。还使肌肉以0.01至100 Hz的频率进行正弦振荡。根据力响应幅度与长度振荡幅度的比值计算肌肉的动态刚度。在低频（<0.2 Hz）时，刚度恒定，但病变肌肉的刚度更大。在0.2 - 1 Hz范围内，动态刚度的大小下降至低频基线的约四分之一。该范围反映横桥周转动力学。对照肌肉中，最小刚度频率为0.78±0.06 Hz，而病变肌肉中为0.42±0.07 Hz。在更高频率时，动态刚度增加并在30 Hz时达到平台期。对照肌肉和病变肌肉达到的平台期无差异。
由于病变心脏的能量储备明显减少，横桥循环速率减慢在人类心力衰竭时观察到的收缩性变化中起重要的适应性作用。尽管正常心脏和病变心脏产生最大钙激活力的潜力相似，但收缩蛋白组成的改变可解释衰竭心脏中横桥循环速率的降低。
