Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, People's Republic of China.
Department of Cardiology, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou City, Jiangsu Province, People's Republic of China.
Hypertens Res. 2017 May;40(5):450-456. doi: 10.1038/hr.2016.169. Epub 2016 Dec 22.
Heart failure with preserved ejection fraction (HFpEF), which is a primary driver of morbidity and mortality, accounts for approximately half of all heart failure cases. Therefore, it is essential to develop preclinical animal models for HFpEF pharmacological treatment strategies. We created a porcine model of severe hypertension and hyperlipidemia by using a combination of deoxycorticosterone acetate (DOCA, 100 mg kg), Western diet (WD) and angiotensin II infusion. Systolic blood pressure, echocardiography and invasive pressure-volume loop were assessed at baseline, 12 weeks and 18 weeks. A detailed histological assessment was also performed to determine the cardiac structural remodeling. Compared with controls (n=10), hypertensive animals (n=10) showed markedly higher systolic blood pressure (181 vs. 86 mm Hg) at 18 weeks. Concentric remodeling, characterized by a normal chamber size with a thicker wall, was observed in hypertensive animals. Left ventricle diastolic function showed a tendency toward decline, according to the echocardiographic data. Hemodynamic data showed that the end-diastolic pressure-volume relationship was elevated without changes in the end-systolic pressure-volume relationship. Histological results revealed that the fibrotic area in hypertensive animals (P<0.05 vs. controls) and the fibrotic area in the posterior wall of hypertensive animals' left atria were larger than other sites of the left atria (P<0.05 vs. other sites). This model can mimic clinical HFpEF to some degree. We found that the posterior wall of the left atrium is more susceptible to atrial remodeling associated with hypertension compared with other regions of the left atrium.
射血分数保留的心力衰竭（HFpEF）是发病率和死亡率的主要驱动因素，约占所有心力衰竭病例的一半。因此，开发用于 HFpEF 药物治疗策略的临床前动物模型至关重要。我们通过使用去氧皮质酮乙酸盐（DOCA，100mgkg）、西方饮食（WD）和血管紧张素 II 输注的组合，创建了一种严重高血压和高血脂的猪模型。在基线、12 周和 18 周时评估收缩压、超声心动图和侵入性压力-容积环。还进行了详细的组织学评估，以确定心脏结构重塑。与对照组（n=10）相比，高血压动物（n=10）在 18 周时的收缩压明显更高（181 对 86mmHg）。高血压动物表现出同心性重塑，其特征是心室大小正常但壁更厚。根据超声心动图数据，左心室舒张功能显示出下降的趋势。血流动力学数据显示，舒张末期压力-容积关系升高，而收缩末期压力-容积关系没有变化。组织学结果表明，高血压动物的纤维化面积（P<0.05 与对照组）和高血压动物左心房后壁的纤维化面积大于左心房的其他部位（P<0.05 与其他部位）。该模型在一定程度上可以模拟临床 HFpEF。我们发现与左心房的其他部位相比，高血压相关的左心房后壁更容易发生心房重塑。
