Distinct time courses and mechanics of right ventricular hypertrophy and diastolic stiffening in a male rat model of pulmonary arterial hypertension
Distinct time courses and mechanics of right ventricular hypertrophy and diastolic stiffening in a male rat model of pulmonary arterial hypertension
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DOI：
10.1152/ajpheart.00046.2021
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发表时间：
2021-10-01
影响因子：
4.8
通讯作者：
Valdez-Jasso, Daniela
中科院分区：
文献类型：
--
作者：
Kwan, Ethan D.;Velez-Rendon, Daniela;Valdez-Jasso, Daniela
虽然肺动脉高压（PAH）导致右心室（RV）肥大和结构重塑，心肌几何和力学性质的变化对收缩和舒张室功能障碍的相对贡献及其时间过程仍然未知。使用测量的RV血流动力学和形态学的变化超过10周的雄性大鼠模型的PAH和RV力学的数学模型，我们歧视的RV几何重塑和心肌材料特性的改变，在收缩和舒张室功能的变化的贡献。显著和快速的右心室肥厚壁增厚足以稳定射血分数，以应对第4周肺动脉压升高，而收缩期肌丝激活无显著变化。第4周后，RV舒张末期压显著增加，舒张末期容积无相应变化。到第5周时，RV舒张室显著僵硬不能用RV肥大解释。相反，模型分析表明，RV舒张末期室僵硬度的增加完全归因于静息心肌材料僵硬度的增加，而这与显著的心肌纤维化或心肌胶原蛋白含量或类型的变化无关。这些研究结果表明，虽然该RV压力超负荷模型中的收缩期容积通过早期RV肥大而稳定，但随后的静息心肌硬化会阻止舒张期扩张。新&值得注意的是，在雄性大鼠模型中使用10周内血液动力学和形态学测量的新型组合。肺动脉高压和RV力学的数学模型，我们发现，代偿性收缩功能几乎完全由右心室肥大解释，但随后右心室舒张末期力学的改变主要由被动心肌硬化解释，这与胶原细胞外基质的显著积累无关。
Although 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 wk 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.NEW & NOTEWORTHY Using a novel combination of hemodynamic and morphological measurements over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we found that compensated systolic function was almost entirely explained by RV hypertrophy, but subsequently altered RV end-diastolic mechanics were primarily explained by passive myocardial stiffening that was not associated with significant collagen extracellular matrix accumulation.