Ndongson-Dongmo Bernadin, Bauer Reinhard, Levy Finn Olav
Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Pharmacology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway.
Exp Physiol. 2025 Sep 17. doi: 10.1113/EP092628.
Millions of people are affected by atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF), two disorders frequently found simultaneously. However, the interrelationship between these intertwined disorders is poorly understood, partly owing to the lack of preclinical models. We aimed to evaluate whether a recently developed mouse model of HFpEF could also be used as a model of AF and, potentially, to study the co-occurrence and interrelationship between the two conditions. Mice were fed a dietary regimen of high-fat diet and N-nitro-l-arginine methyl ester in the drinking water to induce HFpEF. Twenty-four-hour ECG recordings acquired by telemetry were analysed for autonomic imbalance. After 24 h ECG recording, mice received isoprenaline, and a further 1 h of recording was assessed for chronotropic incompetence, susceptibility to atrial arrhythmia and conduction impairment. Evaluation of diastolic function was achieved by transcarotid catheterization and histological analysis performed on the hearts. Resting heart rate was significantly increased after 3 weeks of the dietary regimen, with a trend observed as early as 1 week. Premature atrial contractions, sinus pauses and atrioventricular blocks occurred significantly after 3 weeks of the dietary regimen. Significant diastolic dysfunction, chronotropic incompetence and higher occurrence of AF after isoprenaline stimulation were observed in the HFpEF group at 6 weeks of the dietary regimen. Our study revealed that sinoatrial node and atrial dysfunction precede the simultaneous occurrence of AF, diastolic dysfunction and chronotropic incompetence. This mouse HFpEF model might be helpful for studying the interdependence between AF and HFpEF.
数以百万计的人受到心房颤动（AF）和射血分数保留的心力衰竭（HFpEF）的影响，这两种疾病经常同时出现。然而，人们对这些相互交织的疾病之间的相互关系了解甚少，部分原因是缺乏临床前模型。我们旨在评估最近开发的HFpEF小鼠模型是否也可用于AF模型，并有可能研究这两种情况的同时发生及相互关系。给小鼠喂食高脂肪饮食，并在饮用水中添加N-硝基-L-精氨酸甲酯以诱导HFpEF。通过遥测获取的24小时心电图记录用于分析自主神经失衡。在24小时心电图记录后，小鼠接受异丙肾上腺素，再进行1小时记录，以评估变时功能不全、心房心律失常易感性和传导障碍。通过经颈动脉插管和对心脏进行组织学分析来评估舒张功能。饮食方案3周后静息心率显著增加，早在1周时就观察到这种趋势。饮食方案3周后，房性早搏、窦性停搏和房室传导阻滞显著发生。在饮食方案6周时，HFpEF组在异丙肾上腺素刺激后出现显著的舒张功能障碍、变时功能不全和更高的AF发生率。我们的研究表明，窦房结和心房功能障碍先于AF、舒张功能障碍和变时功能不全同时出现。这种小鼠HFpEF模型可能有助于研究AF和HFpEF之间的相互依存关系。
