Townsend DeWayne
Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota.
Physiol Rep. 2015 Aug;3(8). doi: 10.14814/phy2.12513.
Duchenne muscular dystrophy (DMD) is a progressive striated muscle disease that is characterized by skeletal muscle weakness with progressive respiratory and cardiac failure. Together respiratory and cardiac disease account for the majority of mortality in the DMD patient population. However, little is known regarding the effects of respiratory dysfunction on the dystrophic heart. The studies described here examine the effects of acute hypoxia on cardiac function. These studies demonstrate, for the first time, that a mouse model of DMD displays significant mortality following acute exposure to hypoxia. This mortality is characterized by a steady decline in systolic function. Retrospective analysis reveals that significant decreases in diastolic dysfunction, especially in the right ventricle, precede the decline in systolic pressure. The initial hemodynamic response to acute hypoxia in the mouse is similar to that observed in larger species, with significant increases in right ventricular afterload and decreases in left ventricular preload being observed. Significant increases in heart rate and contractility suggest hypoxia-induced activation of the sympathetic nervous system. These studies provide evidence that while hypoxia presents significant hemodynamic challenges to the dystrophic right ventricle, global cardiac dysfunction precedes hypoxia-induced mortality in the dystrophic heart. These findings are clinically relevant as the respiratory insufficiency evident in patients with DMD results in significant bouts of hypoxia. The results of these studies indicate that hypoxia may contribute to the acceleration of the heart disease in DMD patients. Importantly, hypoxia can be avoided through the use of ventilatory support.
杜氏肌营养不良症（DMD）是一种进行性横纹肌疾病，其特征为骨骼肌无力，并伴有进行性呼吸和心力衰竭。呼吸和心脏疾病共同构成了DMD患者群体的主要死因。然而，关于呼吸功能障碍对营养不良性心脏的影响，人们所知甚少。本文所述的研究探讨了急性缺氧对心脏功能的影响。这些研究首次表明，DMD小鼠模型在急性暴露于缺氧环境后会出现显著的死亡率。这种死亡率的特征是收缩功能持续下降。回顾性分析显示，舒张功能障碍的显著降低，尤其是右心室的舒张功能障碍，先于收缩压的下降。小鼠对急性缺氧的初始血流动力学反应与在较大物种中观察到的相似，表现为右心室后负荷显著增加和左心室前负荷降低。心率和收缩力的显著增加表明缺氧诱导了交感神经系统的激活。这些研究提供了证据，表明虽然缺氧给营养不良性右心室带来了重大的血流动力学挑战，但在营养不良性心脏中，整体心脏功能障碍先于缺氧诱导的死亡。这些发现具有临床相关性，因为DMD患者明显的呼吸功能不全导致了大量的缺氧发作。这些研究结果表明，缺氧可能会加速DMD患者心脏病的发展。重要的是，通过使用通气支持可以避免缺氧。
