STRESS AND STRAIN AS STIMULI FOR MYOCARDIAL GROWTH

描述（改编自申请人的摘要）： 这项研究是为了了解 心肌生长和可能调节这种生长的机械因素 这样人们就能最终了解 适应性心脏肥大恶化为充血性心力衰竭。 它 已经表明，调节肌细胞的主要因素之一 肥大是组织中的压力。 本提案的目的是 以确定不同的分布和多轴模式， 心肌应力和应变影响特定模式的肥大， 心脏的成熟。 由于刺激的确切性质， 肥大仍然未知，申请人认为这些结果将 帮助确定哪些机械因素，如果有的话， 刺激特定的肥大模式。 例如，舒张压 压力、应力或应变刺激离心性心脏肥大 在生理生长？ 一定的装载模式是否有组织地产生 肌原纤维的安排，而其他模式的外部负荷不？ 细胞骨架成分在这些特定的细胞分裂模式中起着什么样的作用？ 肥大？ 病理性心脏肥大可能是由于特定的 加载条件，申请人认为，这些研究将形成 为进一步研究应力和应变的作用奠定了基础， 从生理性肥大到病理性肥大的转变。 回答这些 问题，将在成熟大鼠中测量局部心肌力学 1-6周的年龄。 将通过视频测量心外膜壁应变 在收缩和被动心脏中获得表面标记物。 材料特性以及主动和被动心室 壁应力，将发现与有限元模型的增长 心 为了确定各种应变的直接影响， 肌细胞上的应力模式，分离的肌细胞培养制备物 将用于拉伸静止或跳动的新生肌细胞 在一个可变形的膜上。 申请人假设均匀拉伸 诱导肌原纤维和细胞骨架增殖， 组织，相比之下，更对齐的细胞内结构， 单轴拉伸 此外，申请人提出，细胞骨架 成分在肌原纤维的生长反应中起关键作用， 通过破坏某些细胞骨架结构来验证这一假设， 记录生长反应。 由于肥大性生长会改变 组织应力在没有外部载荷的情况下， 在重建过程中测量。 残余应力是一个因素， 由于个体肥大， 细胞将导致改变的残余应力时，细胞 在完整的组织中汇合。 申请人预计， 计算模型将显示材料特性和内部应力， 包括残余应力，在生长过程中会发生变化。

DESCRIPTION (adapted from the applicant's abstract): The long term goal of this research is to gain an understanding of the relationship between myocardial growth and the mechanical factors which may regulate this growth so that one can eventually gain an understanding of the events by which adaptive cardiac hypertrophy deteriorates into congestive heart failure. It has been suggested that one of the major factors regulating myocyte hypertrophy is the stress in the tissue. The objective of this proposal is to determine how different distributions and multi-axial patterns of myocardial stress and strain affect specific modes of hypertrophy during maturation of the heart. Since the exact nature of the stimulus to hypertrophy remains unknown, the applicant believes that these results will help define which mechanical factors, if any, are responsible for stimulating specific modes of hypertrophy. For example, is diastolic pressure, stress, or strain the stimulus for eccentric cardiac hypertrophy during physiologic growth? Do certain loading pattern produce organized myofibrillar arrangement, while other patterns of external loads do not? What role do cytoskeletal elements play in these specific modes of hypertrophy? Pathologic cardiac hypertrophy may be the result of specific loading conditions, and the applicant believes that these studies will form the basis for further investigations into the role of stress and strain in the transition from physiologic to pathologic hypertrophy. To answer these questions, regional myocardial mechanics will be measured in maturing rats 1-6 weeks of age. Epicardial wall strain will be measured with video acquisition of surface markers in both contracting and passive hearts. Estimates of material properties, as well as active and passive ventricular wall stresses, will be found with finite element models of the growing heart. In order to determine the direct effects of various strain and stress patterns on the myocytes, an isolated myocyte culture preparation will be used in which quiescent or beating neonatal myocytes are stretched on a deformable membrane. The applicant hypothesizes that uniform stretch on a myocyte induces myofibril and cytoskeletal proliferation which is not organized, compared to more aligned intracellular structures in response to a uniaxial stretch. Furthermore, the applicant proposes that cytoskeletal components play a key role in the growth response of the myofibrils and will test this hypothesis by disrupting certain cytoskeletal structures and documenting the growth response. Since hypertrophic growth will change the tissue stress in the absence of external loads, residual strains will be measured during remodeling. Residual stress is one factor that relates the isolated myocyte to the intact tissue since hypertrophy of the individual cell will result in alterations of residual stress when the cells are confluent in the intact tissue. The applicant anticipates that computational models will show material properties and internal stresses, including residual stresses, will change during the growth process.