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Abstract：
Patients with muscular dystrophy have abnormal cardiac function and decreased high-energy phosphate metabolism. Here, we have determined whether the 8 month old mdx mouse, an animal model of muscular dystrophy, also has abnormal cardiac function and energetics. In vivo cardiac MRI revealed 33% and 104% larger right ventricular end-diastolic and end-systolic volumes, respectively, and 17% lower right ventricular ejection fractions in mdx mice compared with controls. Evidence of left ventricular diastolic dysfunction included 18% lower peak filling rates in mdx mouse hearts. Abnormal cardiac function was accompanied by necrosis and lower citrate synthase activity in the mdx mouse heart, suggesting decreased mitochondrial content. Decreased mitochondrial numbers were associated with 38% lower phosphocreatine concentration, 22% lower total creatine, 36% higher cytosolic free ADP concentration and 1.3 kJ/mol lower free-energy available from ATP hydrolysis in whole isolated, perfused mdx mouse hearts than in controls. Transsarcolemmal creatine uptake was 12% lower in mdx mouse hearts. We conclude that the absence of dystrophin in adult mdx mouse heart, as in the heart of human patient, is associated with right ventricular dilatation, left ventricular diastolic dysfunction and abnormal energy metabolism.
摘要：
肌营养不良患者心功能异常，高能磷酸盐代谢下降。这里,我们已经确定了8个月大的MDX鼠标，肌肉营养不良的动物模型,也有心脏功能和能量异常。体内心脏MRI显示右心室舒张末期和收缩末期容积分别增大33%和104%，分别,与对照组相比，mdx小鼠的右心室射血分数降低了17％。左心室舒张功能障碍的证据包括mdx小鼠心脏的峰值充盈率降低了18％。mdx小鼠心脏的心脏功能异常伴随坏死和柠檬酸合酶活性降低，表明线粒体含量下降。线粒体数量减少与磷酸肌酸浓度降低38%相关，总肌酸降低22%，36％更高的细胞溶质游离ADP浓度和1.3kJ/mol更低的自由能可从整个分离的ATP水解，灌注mdx小鼠心脏比对照组。mdx小鼠心脏的肌膜肌酸摄取降低了12％。我们得出结论，成年mdx小鼠心脏中缺乏肌营养不良蛋白，就像人类病人的心脏一样，与右心室扩张有关,左心室舒张功能障碍和能量代谢异常。
