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

右室衰竭可能表明在射血分数保留的情况下，肺动脉高压和心力衰竭等疾病的死亡率更高。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到了损害。本研究项目旨在提高我们对右室的力学行为及其如何影响其泵血功能的了解。粘弹性的概念，指的是心脏组织在收缩和松弛过程中的即时(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。这项研究将包括对右室组织的粘弹性及其对器官功能的影响的全面分析。这项研究的结果可用于护理和管理大约670万心力衰竭患者，预计随着人口老龄化，这一数字将增加。该研究小组计划吸引年轻人，并推进对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工作人员的多样性。研究的目的是发现在急性应激和慢性肺动脉高压下，室壁粘弹性特性如何变化，并影响器官功能。为了表征疾病进展和不同心率下的组织双向粘弹性，将通过应力松弛和循环拉伸实验测量右心室的被动粘弹性，并用我们验证的模型进行计算模拟。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，并对组织粘弹性的变化进行量化。一个新的多尺度本构模型将被用来预测肌纤维和胶原的粘弹性以及胶原的聚集。最后，将通过慢性高血压和急性应激改变的右室粘弹性来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生和初中生分发各种STEM工具包，参加校园内现有的K-12公共推广活动。此外，还将对代表不足的本科生和研究生进行培训和指导。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.