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藏猪小型心力衰竭伴射血分数保留的手术模型。

A Surgical Model of Heart Failure with Preserved Ejection Fraction in Tibetan Minipigs.

机构信息

Guangdong Laboratory Animals Monitoring Institute; Department of Cardiovascular Surgery, the First Affiliated Hospital, Jinan University.

Guangdong Laboratory Animals Monitoring Institute; College of Veterinary Medicine, South China Agricultural University.

出版信息

J Vis Exp. 2022 Feb 18(180). doi: 10.3791/63526.

Abstract

More than half of heart failure (HF) cases are classified as heart failure with preserved ejection fraction (HFpEF) worldwide. Large animal models are limited for investigating the fundamental mechanisms of HFpEF and identifying potential therapeutic targets. This work provides a detailed description of the surgical procedure of descending aortic constriction (DAC) in Tibetan minipigs to establish a large animal model of HFpEF. This model used a precisely controlled constriction of the descending aorta to induce chronic pressure overload in the left ventricle. Echocardiography was used to evaluate the morphological and functional changes in the heart. After 12 weeks of DAC stress, the ventricular septum was hypertrophic, but the thickness of the posterior wall was significantly reduced, accompanied by dilation of the left ventricle. However, the LV ejection fraction of the model hearts was maintained at >50% during the 12-week period. Furthermore, the DAC model displayed cardiac damage, including fibrosis, inflammation, and cardiomyocyte hypertrophy. Heart failure marker levels were significantly elevated in the DAC group. This DAC-induced HFpEF in minipigs is a powerful tool for investigating molecular mechanisms of this disease and for preclinical testing.

摘要

全球范围内,超过一半的心衰(HF)病例被归类为射血分数保留的心衰(HFpEF)。大型动物模型在研究 HFpEF 的基本机制和确定潜在治疗靶点方面受到限制。本研究详细描述了在西藏小型猪中进行降主动脉缩窄(DAC)的手术过程,以建立 HFpEF 的大型动物模型。该模型通过精确控制降主动脉的缩窄来诱导左心室的慢性压力超负荷。超声心动图用于评估心脏的形态和功能变化。在 DAC 应激 12 周后,室间隔肥厚,但后壁厚度显著减少,左心室扩张。然而,模型心脏的 LV 射血分数在 12 周期间保持在>50%。此外,DAC 模型显示出心脏损伤,包括纤维化、炎症和心肌细胞肥大。心衰标志物水平在 DAC 组显著升高。这种 DAC 诱导的小型猪 HFpEF 是研究该疾病分子机制和临床前测试的有力工具。

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