Khuchua Z A, Vasiljeva E V, Clark J F, Korchazhkina O V, Branishte T, Kapelko V I, Kuznetsov A V, Ventura-Clapier R, Lakomkin V L
Laboratory of Bioenergetics, USSR Research Center for Cardiology, Moscow.
Am J Cardiovasc Pathol. 1992;4(3):223-34.
Changes in the creatine kinase system, cellular energetics, regulation of respiration and alterations in parameters of contractility in experimental animals (myopathic hamsters), and in patients with dilated cardiomyopathy were studied. 31P-NMR methods were used to show that cardiomyopathic hearts are characterized by decreased work index, lower tissue ATP, phosphocreatine, and total creatine contents and diminished creatine kinase activity and energy fluxes. In isolated mitochondria, only the creatine kinase activity was decreased. Both in cardiomyopathic hamsters and human hearts a share of mitochondrial creatine kinase in the total tissue enzyme activity was decreased from 33% to 18% and that of BB elevated from 5% in control to 20%, at an unchanged relative level of MM. In saponins-skinned cardiac fibers on cardiomyocytes creatine (Cr, 25 mM) decreased Km for ADP in regulation of respiration from 133 +/- 20 to 20 +/- 4 microM due to activation of coupled mitochondrial creatine kinase-oxidative phosphorylation reactions in control hamster hearts. In the case of cardiomyopathy it decreased Km for ADP only to 81 +/- 13 microM. In endocardial biopsy samples from the hearts of patients with dilated cardiomyopathy taken during angiography, creatine stimulated respiration was decreased by 36% of control value, which correlated well with increase of end-diastolic pressure and fall in ejection fraction. Thus, changes in mitochondrial creatine kinase expression diminished the efficiency of cellular regulation of respiration in cardiomyopathic hearts that may have functional consequences for hemodynamics or may be adaptive alterations in response to decreased contractility.
对实验动物（患肌病的仓鼠）以及扩张型心肌病患者体内肌酸激酶系统的变化、细胞能量代谢、呼吸调节和收缩性参数改变进行了研究。采用³¹P-NMR方法表明，患心肌病的心脏具有工作指数降低、组织ATP、磷酸肌酸和总肌酸含量较低、肌酸激酶活性和能量通量减少的特征。在分离的线粒体中，只有肌酸激酶活性降低。在患心肌病的仓鼠和人类心脏中，线粒体肌酸激酶在总组织酶活性中的占比从33%降至18%，而BB型的占比从对照组的5%升至20%，MM型的相对水平保持不变。在对照仓鼠心脏中，皂苷透皮处理的心肌细胞肌纤维上的肌酸（Cr，25 mM）可将呼吸调节中ADP的Km值从133±20 μM降至20±4 μM，这是由于线粒体肌酸激酶 - 氧化磷酸化偶联反应的激活。在心肌病的情况下，它仅将ADP的Km值降至81±13 μM。在血管造影期间取自扩张型心肌病患者心脏的心内膜活检样本中，肌酸刺激的呼吸降低至对照值的36%，这与舒张末期压力升高和射血分数下降密切相关。因此，线粒体肌酸激酶表达的变化降低了患心肌病心脏中细胞呼吸调节的效率，这可能对血液动力学产生功能影响，或者可能是对收缩性降低的适应性改变。
