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Large animal models of heart failure with preserved ejection fraction
Heart Failure Reviews ( IF 4.6 ) Pub Date : 2021-11-09 , DOI: 10.1007/s10741-021-10184-9
Chihiro Miyagi 1 , Takuma Miyamoto 1 , Taiyo Kuroda 1 , Jamshid H Karimov 1 , Randall C Starling 2, 3 , Kiyotaka Fukamachi 1
Affiliation  

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and multiple comorbidities. The number of patients is continuously increasing, with no improvement in its unfavorable prognosis, and there is a strong need for novel treatments. New devices and drugs are difficult to assess at the translational preclinical step due to the lack of high-fidelity large animal models of HFpEF. In this review, we describe the summary of historical and evolving techniques for developing large animal models. The representative methods are pressure overload models, including (1) aortic banding, (2) aortic stent, (3) renal hypertension, and (4) mineralocorticoid-induced hypertension. Diet-induced metabolic syndromes are also used. A new technique with an inflatable balloon inside the left ventricle can be used during acute/chronic in vivo surgeries to simulate HFpEF-like hemodynamics for pump-based therapies. Canines and porcine are most widely used, but other non-rodent animals (sheep, non-human primates, felines, or calves) have been used. Feline models present the most well-simulated HFpEF pathology, but small size is a concern, and the information is still very limited. The rapid and reliable establishment of large animal models for HFpEF, and novel methodology based on the past experimental attempts with large animals, are needed.



中文翻译:

射血分数保留的心力衰竭大型动物模型

射血分数保留型心力衰竭 (HFpEF) 的特点是舒张功能障碍和多种合并症。患者数量不断增加,其不良预后没有改善,迫切需要新的治疗方法。由于缺乏 HFpEF 的高保真大型动物模型,新设备和药物难以在临床前转化阶段进行评估。在这篇综述中,我们总结了开发大型动物模型的历史和不断发展的技术。具有代表性的方法是压力过载模型,包括(1)主动脉束带、(2)主动脉支架、(3)肾性高血压和(4)盐皮质激素诱发的高血压。饮食诱导的代谢综合征也被使用。在急性/慢性体内手术期间,可以使用一种在左心室内带有充气球囊的新技术来模拟基于泵的疗法的类似 HFpEF 的血流动力学。犬科动物和猪使用最广泛,但也使用了其他非啮齿动物(绵羊、非人类灵长类动物、猫科动物或小牛)。猫科动物模型呈现了最能模拟的 HFpEF 病理学,但体积小是一个问题,而且信息仍然非常有限。需要快速可靠地建立 HFpEF 大型动物模型,以及基于过去对大型动物的实验尝试的新方法。猫科动物模型呈现了最能模拟的 HFpEF 病理学,但体积小是一个问题,而且信息仍然非常有限。需要快速可靠地建立 HFpEF 大型动物模型,以及基于过去对大型动物的实验尝试的新方法。猫科动物模型呈现了最能模拟的 HFpEF 病理学,但体积小是一个问题,而且信息仍然非常有限。需要快速可靠地建立 HFpEF 大型动物模型,以及基于过去对大型动物的实验尝试的新方法。

更新日期:2021-11-10
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