糖尿病患者对血栓栓塞事件的易感性增加,在大多数情况下,起源于左心耳(LAA)的血栓。LAA的重塑,容易形成血栓,以前曾在糖尿病合并房颤患者中描述过,但糖尿病患者在没有房颤的情况下是否也会发生LAA重塑尚不清楚.为了调查糖尿病的贡献,与心房颤动相反,重建LAA,我们从人类到动物模型。
我们通过超声心动图研究了科恩糖尿病敏感大鼠(CD/y)在糖尿病演变过程中的多个时间点的心脏结构和功能,该大鼠提供了4个月的糖尿病饮食;CD/y提供了常规饮食和科恩糖尿病抗性(CDr/y),不会发展为糖尿病,作为控制。在整个研究期间,所有动物都处于窦性心律。
与对照相比,CDs/y在糖尿病的演变过程中产生了更大的心脏质量,左心房直径较大,较宽的左心耳孔口,LAA深度增加,舒张末期和收缩末期直径较大,和较低的E/A比-都表明左心耳和左心房(LA)的重塑,以及左心室舒张功能障碍的发展。为了调查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CD/Y中发现,但在其他任何群体中都没有,心耳中有丰富的糖原颗粒,心房和心室,这可能具有重要意义,因为糖原颗粒以前与糖尿病心脏的细胞和器官功能障碍有关。
我们得出结论,我们的啮齿动物糖尿病模型,这是窦性心律,复制了先前在患有房颤的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,LAA和LA的重塑与心房颤动无关,并且与糖原颗粒的积累有关。我们认为糖原颗粒的心肌积累与糖尿病的发展有关,可能在LAA和LA的重塑中起病理生理作用。容易导致心房颤动,糖尿病心脏的血栓栓塞事件和左心室舒张功能障碍。
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.