Diabetic patients have an increased predisposition to thromboembolic events, in most cases originating from thrombi in the left atrial appendage (LAA). Remodeling of the LAA, which predisposes to thrombi formation, has been previously described in diabetic patients with atrial fibrillation, but whether remodeling of the LAA occurs in diabetics also in the absence of atrial fibrillation is unknown. To investigate the contribution of diabetes, as opposed to atrial fibrillation, to remodeling of the LAA, we went from humans to the animal model. We studied by echocardiography the structure and function of the heart over multiple time points during the evolution of diabetes in the Cohen diabetic sensitive rat (CDs/y) provided diabetogenic diet over a period of 4 months; CDs/y provided regular diet and the Cohen diabetic resistant (CDr/y), which do not develop diabetes, served as controls. All animals were in sinus rhythm throughout the study period. Compared to controls, CDs/y developed during the evolution of diabetes a greater heart mass, larger left atrial diameter, wider LAA orifice, increased LAA depth, greater end-diastolic and end-systolic diameter, and lower E/A ratio—all indicative of remodeling of the LAA and left atrium (LA), as well as the development of left ventricular diastolic dysfunction. To investigate the pathophysiology involved, we studied the histology of the hearts at the end of the study. We found in diabetic CDs/y, but not in any of the other groups, abundance of glycogen granules in the atrial appendages , atria and ventricles, which may be of significance as glycogen granules have previously been associated with cell and organ dysfunction in the diabetic heart. We conclude that our rodent model of diabetes, which was in sinus rhythm, reproduced structural and functional alterations previously observed in hearts of human diabetics with atrial fibrillation. Remodeling of the LAA and of the LA in our model was unrelated to atrial fibrillation and associated with accumulation of glycogen granules. We suggest that myocardial accumulation of glycogen granules is related to the development of diabetes and may play a pathophysiological role in remodeling of the LAA and LA, which predisposes to atrial fibrillation, thromboembolic events and left ventricular diastolic dysfunction in the diabetic heart.

中文翻译：

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在 2 型糖尿病啮齿动物模型中，糖尿病诱导左心耳重塑，与心房颤动无关


糖尿病患者更容易发生血栓栓塞事件，大多数情况下源自左心耳 (LAA) 的血栓。先前已在患有心房颤动的糖尿病患者中描述了容易形成血栓的左心耳重塑，但在没有心房颤动的糖尿病患者中是否也会发生左心耳重塑尚不清楚。为了研究糖尿病（而不是心房颤动）对左心耳重塑的影响，我们从人类模型转向动物模型。我们通过超声心动图研究了在 4 个月内提供致糖尿病饮食的 Cohen 糖尿病敏感大鼠 (CDs/y) 在糖尿病演变过程中多个时间点的心脏结构和功能； CDs/y 提供常规饮食，而 Cohen 糖尿病抵抗者 (CDr/y)（不会发展为糖尿病）作为对照。在整个研究期间所有动物均处于窦性心律。与对照组相比，CDs/y 在糖尿病的发展过程中出现了更大的心脏质量、更大的左心房直径、更宽的左心耳孔、增加的左心耳深度、更大的舒张末期和收缩末期直径以及更低的 E/A 比——所有这些都表明LAA 和左心房 (LA) 的重塑，以及左心室舒张功能障碍的发展。为了研究所涉及的病理生理学，我们在研究结束时研究了心脏的组织学。我们在糖尿病 CDs/y 中发现心耳、心房和心室中存在丰富的糖原颗粒，但在任何其他组中均未发现，这可能具有重要意义，因为糖原颗粒先前已被认为与糖尿病患者的细胞和器官功能障碍有关。心。 我们得出的结论是，我们的糖尿病啮齿动物模型处于窦性节律，再现了先前在患有房颤的人类糖尿​​病患者心脏中观察到的结构和功能改变。在我们的模型中，左心耳和左心耳的重塑与心房颤动无关，但与糖原颗粒的积累有关。我们认为，心肌糖原颗粒的积累与糖尿病的发生有关，并且可能在左心耳和左心耳的重塑中发挥病理生理作用，从而诱发糖尿病心脏的心房颤动、血栓栓塞事件和左心室舒张功能障碍。