Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension

右心室衰竭可提示肺动脉高压和保留射血分数的心力衰竭等疾病的死亡风险较高。患有这些疾病的人经常报告运动不耐受，这表明他们对身体压力的反应受损。本研究项目旨在提高我们对右心室的机械行为及其如何影响其泵送功能的理解。粘弹性的概念是指心脏组织在收缩和松弛期间的即时（弹性）和延迟（粘性）阻力，将用于研究细胞行为和心脏的整体性能如何受到影响。该研究将包括对右心室组织的粘弹性及其对器官功能的影响的全面分析。该研究结果可用于约670万心力衰竭患者的护理和管理，预计随着人口老龄化，心力衰竭患者将增加。该研究团队计划吸引年轻人，推进下一代生物工程师的教育，重点是指导女性和第一代学生，以增强STEM劳动力的多样性。本研究旨在探讨急性应激和慢性肺动脉高压对心室壁粘弹性特性的影响及对脏器功能的影响。为了描述疾病进展和不同心率下的组织双轴粘弹性，右心室的被动粘弹性将通过应力松弛和周期性拉伸试验进行实验测量，并使用我们验证的模型进行模拟计算。为了揭示细胞和细胞外成分对组织粘弹性的贡献，将进行药物治疗以解聚微管和降解胶原，并量化组织粘弹性的变化。将建立一个新的多尺度本构模型来预测肌纤维和胶原蛋白的粘弹性以及胶原蛋白的募集。最后，用慢性高血压和急性应激改变的右心室粘弹性测量器官功能的变化。教育活动包括向科罗拉多州北部的小学和初高中学生分发各种STEM工具包，参与校园内现有的K-12公共宣传活动。此外，还将对代表性不足的本科生和研究生进行培训和指导。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The failure of the right ventricle can indicate a higher risk of mortality in diseases like pulmonary hypertension and heart failure with preserved ejection fraction. People with these diseases often report exercise intolerance, which suggests that their response to physical stress is impaired. This research project aims to improve our understanding of the mechanical behavior of the right ventricle and how it affects its pumping function. The concept of viscoelasticity, which refers to the immediate (elastic) and delayed (viscous) resistance of cardiac tissue during contraction and relaxation, will be used to study how cellular behavior and the overall performance of the heart are affected. The research will include a comprehensive analysis of the viscoelasticity of the right ventricle tissue and its implications in organ function. The findings of this study could be used to the care and management of approximately 6.7 million heart failure patients, which are projected to increase with the aging population. The research team plans to engage young minds and advance the education of the next generation of bioengineers, with a focus on mentoring women and first-generation students to enhance diversity in the STEM workforce.The aim of the research is to discover how the ventricle wall viscoelastic properties change under acute stress and chronic pulmonary hypertension and impact organ function. To characterize the tissue biaxial viscoelasticity with disease progression and at varied heart rates, the passive viscoelasticity of the right ventricle will be measured experimentally by stress relaxation and cyclical tensile tests and simulated computationally with our validated models. To reveal the cellular and extracellular components’ contributions to tissue viscoelasticity, drug treatment will be performed to depolymerize microtubules and degrade collagen and changes in tissue viscoelasticity will be quantified. A new multiscale constitutive model will be developed to predict the viscoelasticity of myofibers and collagen as well as collagen recruitment. Finally, organ function changes will be measured with right ventricle viscoelasticity altered by chronic hypertension and acute stress. Educational activities include the distribution of various STEM kits to elementary and middle-to-high school students in northern Colorado, participation in existing K-12 public outreach events on campus. Additionally, there will be training and mentoring of underrepresented undergraduate and graduate students.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.