PDF(Pubmed)
Abstract：
Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis (AS). AS 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. At a cellular level, this corresponds to a considerable increase in the size of cardiomyocytes, known as cardiomyocyte hypertrophy, while 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 AS 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 physiological, cellular and molecular mechanisms that sufficiently resemblance humans and 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 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 at prevention of the disease progress or, alternatively, at 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 currently better mimic the condition.
摘要：
病理性心肌肥厚是许多心血管疾病的常见后果，包括主动脉狭窄.已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，这将逐渐导致扩张和心力衰竭。在细胞层面，这对应于心肌细胞大小的显著增加，命名为心肌细胞肥大，因为它们的增殖能力在第一个发育阶段减弱。心肌细胞,为了应对增加的工作量(过载)，遭受形态的改变，核含量,能量代谢，细胞内稳态机制，收缩活动和细胞死亡机制。此外，心肌细胞生态位的改变，涉及炎症，免疫浸润，纤维化和血管生成，有助于病理性肥大反应的后续事件。考虑到需要更好地了解病情和治疗改善，由于主动脉狭窄的唯一可用治疗选择包括疾病晚期的手术干预，当心肌状态不可逆时，已经开发了大型动物模型来模仿人类状况，到最大程度。较小的动物模型缺乏与人类足够相似的生理学以及细胞和分子机制;体外技术还不能提供足够的复杂性。动物,例如雪貂（Mustellopurtoriusfuro），lapine(兔子，Oryctolaguscunigulus)，猫科动物（猫，Feliscatus)，犬（狗，犬狼疮家族），绵羊（绵羊，Ovisaries)和猪(猪，Susscrofa)，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。在这篇综述中简要报告和讨论了每个模型的基本发现。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，或者，涉及的病理机制回归到生理状态。这篇综述总结了LV肥大的病理生理学的重要方面，以及应用于外科手术的大型动物模型，这些模型可以更好地模拟目前的状况。
