Background: Left ventricular wall motion is depressed in patients with dilated cardiomyopathy (DCM). However, whether or not the depressed left ventricular wall motion is caused by impairment of sarcomere dynamics remains to be fully clarified.

Methods and Results: We analyzed the mechanical properties of single sarcomere dynamics during sarcomeric auto-oscillations (calcium spontaneous oscillatory contractions [Ca-SPOC]) that occurred at partial activation under the isometric condition in myofibrils from donor hearts and from patients with severe DCM (New York Heart Association classification III-IV). Ca-SPOC reproducibly occurred in the presence of 1 μmol/L free Ca²⁺ in both nonfailing and DCM myofibrils, and sarcomeres exhibited a saw-tooth waveform along single myofibrils composed of quick lengthening and slow shortening. The period of Ca-SPOC was longer in DCM myofibrils than in nonfailing myofibrils, in association with prolonged shortening time. Lengthening time was similar in both groups. Then, we performed Tn (troponin) exchange in myofibrils with a DCM-causing homozygous mutation (K36Q) in cTnI (cardiac TnI). On exchange with the Tn complex from healthy porcine ventricles, period, shortening time, and shortening velocity in cTnI-K36Q myofibrils became similar to those in Tn-reconstituted nonfailing myofibrils. Protein kinase A abbreviated period in both Tn-reconstituted nonfailing and cTnI-K36Q myofibrils, demonstrating acceleration of cross-bridge kinetics.

Conclusions: Sarcomere dynamics was found to be depressed under loaded conditions in DCM myofibrils because of impairment of thick-thin filament sliding. Thus, microscopic analysis of Ca-SPOC in human cardiac myofibrils is beneficial to systematically unveil the kinetic properties of single sarcomeres in various types of heart disease.

背景：扩张型心肌病（DCM）患者的左心室壁运动受压。但是，是否由肌节动力学的损害引起左心室壁运动下降尚有待充分阐明。

方法和结果：我们分析了在等轴测条件下肌原纤维中供体心脏和重度DCM（重度DCM（纽约心脏协会分类III-IV）。在1μmol/ L游离Ca ²⁺存在下可重复发生Ca-SPOC在未失败和DCM的肌原纤维中，肉瘤沿单个肌原纤维表现出锯齿状波形，包括快速延长和缓慢缩短。DCM肌原纤维中Ca-SPOC的时间比未失败的肌原纤维中的Ca-SPOC的时间更长，且缩短的时间也较长。两组的延长时间相似。然后，我们在肌原纤维中进行了Tn（肌钙蛋白）交换，并在DCM中引起了cTnI（心脏TnI）的纯合突变（K36Q）。与健康猪脑室中的Tn复合物交换后，cTnI-K36Q肌原纤维中的周期，缩短时间和缩短速度变得与Tn重构的未失败肌原纤维中的相似。在Tn重构的未失败和cTnI-K36Q肌原纤维中，蛋白激酶A的缩短期，证明了跨桥动力学的加速。

结论：发现在负荷条件下，DCM肌原纤维的肌节动力学降低，这是由于细丝滑动的受损所致。因此，人类心脏肌原纤维中Ca-SPOC的显微分析有利于系统地揭示各种类型心脏病中单个肉瘤的动力学特性。