Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis. Aortic stenosis is known to increase the pressure load of the left ventricle, causing a compensative response of the cardiac muscle, which progressively will lead to dilation and heart failure. In a cellular level, this corresponds to a considerable increase in the size of cardiomyocytes, named cardiomyocyte hypertrophy, as their proliferation capacity is attenuated upon the first developmental stages. Cardiomyocytes, in order to cope with the increased workload (overload), suffer alterations in their morphology, nuclear content, energy metabolism, intracellular homeostatic mechanisms, contractile activity and cell death mechanisms. Moreover, modifications in the cardiomyocyte niche, involving inflammation, immune infiltration, fibrosis and angiogenesis, contribute to the subsequent events of a pathologic hypertrophic response. Considering the emerging need for a better understanding of the condition and treatment improvement, as the only available treatment option of aortic stenosis consists of surgical interventions at a late stage of the disease, when the cardiac muscle state is irreversible, large animal models have been developed to mimic the human condition, to the greatest extend. Smaller animal models lack physiology and cellular and molecular mechanisms that sufficiently resemblance humans; in vitro techniques yet fail to provide adequate complexity. Animals, such as the ferret (Mustello purtorius furo), lapine (rabbit, Oryctolagus cunigulus), feline (cat, Felis catus), canine (dog, Canis lupus familiaris), ovine (sheep, Ovis aries) and porcine (pig, Sus scrofa), have contributed to the research by elucidating implicated cellular and molecular mechanisms of the condition. Essential discoveries of each model are reported and discussed briefly in this review. Results of large animal experimentation could further be interpreted aiming to the prevention of the disease progress or, alternatively, to the regression of the implicated pathologic mechanisms to a physiologic state. This review summarizes the important aspects of the pathophysiology of LV hypertrophy and the applied surgical large animal models that better mimic the condition until the present moment.

中文翻译：

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压力超负荷引起的心脏左心室肥大的大型动物模型，用于研究主动脉瓣狭窄的人心脏重塑

病理性心脏肥大是许多心血管疾病（包括主动脉瓣狭窄）的常见后果。众所周知，主动脉瓣狭窄会增加左心室的压力负荷，引起心肌的代偿反应，从而逐渐导致扩张和心力衰竭。在细胞水平上，这对应于心肌细胞大小的显着增加，称为心肌细胞肥大，因为它们的增殖能力在第一个发育阶段减弱。为了应对增加的工作负荷（超负荷），心肌细胞的形态、核含量、能量代谢、细胞内稳态机制、收缩活性和细胞死亡机制都会发生改变。此外，心肌细胞生态位的改变，包括炎症、免疫浸润、纤维化和血管生成，导致病理性肥大反应的后续事件。考虑到更好地了解病情和改进治疗的需求，由于主动脉瓣狭窄唯一可用的治疗选择包括在疾病晚期进行手术干预，此时心肌状态不可逆转，因此开发了大型动物模型最大程度地模仿人类的状况。较小的动物模型缺乏与人类足够相似的生理学、细胞和分子机制；体外技术尚未提供足够的复杂性。动物，如雪貂 (Mustello purtorius Furo)、拉皮恩 (兔子、Oryctolagus cunigulus)、猫科动物 (猫、Felis catus)、犬科动物 (狗、Canis lupusamilis)、绵羊 (绵羊、Ovis aries) 和猪 (猪、Sus) scrofa）通过阐明该疾病的相关细胞和分子机制为研究做出了贡献。本综述简要报告并讨论了每个模型的重要发现。大型动物实验的结果可以进一步解释，旨在预防疾病进展，或者使所涉及的病理机制回归生理状态。这篇综述总结了左心室肥厚病理生理学的重要方面以及迄今为止更好地模拟这种情况的外科大型动物模型的应用。