While pulmonary arterial hypertension (PAH) leads to right ventricle (RV) hypertrophy and structural remodeling, the relative contributions of changes in myocardial geometric and mechanical properties to systolic and diastolic chamber dysfunction and their time courses remain unknown. Using measurements of RV hemodynamic and morphological changes over 10 weeks in a male rat model of PAH and a mathematical model of RV mechanics, we discriminated the contributions of RV geometric remodeling and alterations of myocardial material properties to changes in systolic and diastolic chamber function. Significant and rapid RV hypertrophic wall thickening was sufficient to stabilize ejection fraction in response to increased pulmonary arterial pressure by week 4 without significant changes in systolic myofilament activation. After week 4, RV end-diastolic pressure increased significantly with no corresponding changes in end-diastolic volume. Significant RV diastolic chamber stiffening by week 5 was not explained by RV hypertrophy. Instead, model analysis showed that the increases in RV end-diastolic chamber stiffness were entirely attributable to increased resting myocardial material stiffness that was not associated with significant myocardial fibrosis or changes in myocardial collagen content or type. These findings suggest that whereas systolic volume in this model of RV pressure overload is stabilized by early RV hypertrophy, diastolic dilation is prevented by subsequent resting myocardial stiffening.

中文翻译：

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肺动脉高压雄性大鼠模型右心室肥厚和舒张期强直的不同时间进程和机制

虽然肺动脉高压 (PAH) 导致右心室 (RV) 肥大和结构重塑，但心肌几何和机械特性的变化对收缩和舒张腔功能障碍及其时间过程的相对贡献仍然未知。使用 PAH 雄性大鼠模型 10 周内 RV 血流动力学和形态学变化的测量值和 RV 力学的数学模型，我们区分了 RV 几何重构和心肌材料特性改变对收缩和舒张腔功能变化的贡献。到第 4 周，显着且快速的 RV 肥厚壁增厚足以稳定射血分数，以响应肺动脉压升高，而收缩肌丝激活没有显着变化。第 4 周后，RV 舒张末期压力显着增加，而舒张末期容积没有相应变化。RV 肥大不能解释第 5 周显着的 RV 舒张室僵硬。相反，模型分析显示 RV 舒张末期腔室硬度的增加完全归因于静息心肌材料硬度的增加，而这与显着的心肌纤维化或心肌胶原含量或类型的变化无关。这些发现表明，虽然这种 RV 压力超负荷模型中的收缩容积通过早期 RV 肥大稳定，但随后的静息心肌僵硬阻止了舒张期扩张。相反，模型分析显示 RV 舒张末期腔室硬度的增加完全归因于静息心肌材料硬度的增加，而这与显着的心肌纤维化或心肌胶原含量或类型的变化无关。这些发现表明，虽然这种 RV 压力超负荷模型中的收缩容积通过早期 RV 肥大稳定，但随后的静息心肌僵硬阻止了舒张期扩张。相反，模型分析显示 RV 舒张末期腔室硬度的增加完全归因于静息心肌材料硬度的增加，而这与显着的心肌纤维化或心肌胶原含量或类型的变化无关。这些发现表明，虽然这种 RV 压力超负荷模型中的收缩容积通过早期 RV 肥大稳定，但随后的静息心肌僵硬阻止了舒张期扩张。