STRESS AND STRAIN AS STIMULI FOR MYOCARDIAL GROWTH

描述(改编自申请人的摘要)：长期目标 这项研究是为了了解两者之间的关系 心肌生长及其可能调节的机械因素 这样一来，人们最终就可以对事件有一个了解 适应性心肌肥厚恶化为充血性心力衰竭。它 已被认为是调节心肌细胞的主要因素之一 肥大是组织中的压力。这项提议的目标是 确定不同的分布和多轴模式 心肌应力和应变影响心肌肥厚的特定模式 心脏的成熟。由于刺激的确切性质是 肥大尚不清楚，申请人相信这些结果将 帮助定义哪些机械因素(如果有的话)负责 刺激特定的肥大模式。例如，是舒张期 压力、应激或使刺激产生偏心性心肌肥厚 在生理生长过程中？一定的装车模式是否有条理？ 肌原纤维排列，而其他模式的外部负荷不是吗？ 细胞骨架元素在这些特定模式中扮演什么角色？ 肥大？病理性心肌肥大可能是特发性心肌肥大的结果 加载条件，申请人相信这些研究将形成 进一步研究应力和应变在 从生理性肥大到病理性肥大的转变。要回答这些问题 问题，将在成熟的大鼠中测量局部心肌力学 1-6周龄。心外膜壁应变将通过视频测量 在收缩和被动心脏中获得表面标记。 材料特性的估计，以及主动和被动心脏 墙体应力，会随着有限元模型的增长而增长 心。为了确定各种菌株的直接影响和 分离的心肌细胞培养制剂--心肌细胞的应力模式 将用于拉伸静止或跳动的新生儿心肌细胞 在可变形的薄膜上。申请者假设制服伸展 在肌细胞上诱导肌原纤维和细胞骨架的增殖，而不是 有组织的，与细胞内更排列的结构相比，以响应 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着关键作用 通过破坏某些细胞骨架结构来验证这一假设 记录增长反应。因为肥大的生长会改变 组织应力在没有外载荷的情况下，残余应变会 在改建过程中测量。残余应力是影响材料性能的因素之一。 自个体肥大以来分离的心肌细胞至完整组织 当细胞被分解时，细胞会引起残余应力的变化 融合在完整的组织中。申请人预计到 计算模型将显示材料属性和内部应力， 包括残余应力在内，都会在生长过程中发生变化。

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.