Long-term severe diabetes only leads to mild cardiac diastolic dysfunction in Zucker diabetic fatty rats
Long-term severe diabetes only leads to mild cardiac diastolic dysfunction in Zucker diabetic fatty rats
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DOI：
10.1093/eurjhf/hfr166
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发表时间：
2012-02-01
影响因子：
18.2
通讯作者：
van Nieuwenhoven, Frans A.
中科院分区：
文献类型：
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作者：
Daniels, Anneleen;Linz, Dominik;van Nieuwenhoven, Frans A.
目的2型糖尿病（DM）导致心脏功能不全，与高血压和冠状动脉疾病无关;这被称为糖尿病心肌病。在这里，我们调查了老年Zucker糖尿病脂肪（ZDF）rats.Methods和结果体重，血糖和糖化血红蛋白（Hb（A1 c））水平，尿白蛋白排泄的糖尿病心肌病和心肌重塑的严重程度进行了定期监测ZDF大鼠（n = 19）和对照组（n = 19）年龄45周。在整个研究期间，ZDF大鼠患有重度糖尿病，并在处死时表现出体重和心脏重量下降。在44周龄时使用磁共振成像（MRI）测定左心室（LV）功能，结果显示对照组和ZDF大鼠的LV射血分数和心输出量指数相似，表明收缩功能保留。ZDF大鼠在45周龄时评估的LV压力特征显示LV舒张末期压（+45%）和舒张时间常数Tau（+54%）显著但轻度升高，表明舒张功能障碍。组织学分析显示，左心室胶原含量显着增加（+50%），但没有心肌细胞肥大ZDF rats.Conclusion本研究清楚地表明，长期，严重的DM在45周龄ZDF大鼠导致相对轻度的左心室舒张功能受损，而收缩功能保存良好。这些数据不支持糖尿病本身是诱导临床相关程度心功能不全的关键因素的观点。高血压和冠状动脉疾病等合并症可能对糖尿病患者的心肌功能有更大的影响。
Aims Type 2 diabetes mellitus (DM) leads to cardiac dysfunction irrespective of hypertension and coronary artery disease; this is called diabetic cardiomyopathy. Here, we investigated the severity of diabetic cardiomyopathy and myocardial remodelling in aged Zucker diabetic fatty (ZDF) rats.Methods and results Body weight, blood glucose and glycated haemoglobin (Hb(A1c)) levels, and urinary albumin excretion were monitored regularly in ZDF rats (n = 19) and control littermates (n = 19) up to age 45 weeks. ZDF rats were severely diabetic during the entire study period and demonstrated decreased body and heart weights at sacrifice. Left ventricular (LV) function was determined using magnetic resonance imaging (MRI) at age 44 weeks and revealed similar LV ejection fraction and cardiac output index in control and ZDF rats, indicating preserved systolic function. LV pressure characteristics assessed at age 45 weeks showed significant, but mild elevations of LV end-diastolic pressure (+45%) and relaxation time constant Tau (+54%) in ZDF rats, indicating diastolic dysfunction. Histological analyses revealed a significantly increased LV collagen content (+50%), but no cardiomyocyte hypertrophy in ZDF rats.Conclusion The present study clearly shows that long term, severe DM in 45-week-old ZDF rats resulted in relatively mild impairment of diastolic LV function, whereas systolic function was well preserved. These data do not support the notion that diabetes per se is a critical factor in the induction of a clinically relevant degree of cardiac dysfunction. Co-morbidities such as hypertension and coronary artery disease probably have larger impacts on myocardial function in diabetic individuals.