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

合作研究：急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响

• 批准号: 2244996
• 负责人: Naomi Chesler
• 金额: $ 8.34万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2244996&HistoricalAwards=false
• 关键词: Collaborative; Research; Changes; Impact; Right

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.

右心室衰竭可能表明肺动脉高压和射血分数正常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到损害。该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功能的理解。粘弹性的概念是指心脏组织在收缩和舒张期间的即时（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。这项研究将包括对右心室组织粘弹性及其对器官功能的影响的综合分析。这项研究的结果可用于约670万心力衰竭患者的护理和管理，预计随着人口老龄化而增加。该研究团队计划吸引年轻人的参与，并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。该研究的目的是发现心室壁粘弹性如何在急性应激和慢性肺动脉高压下发生变化，并影响器官功能。为了表征随着疾病进展和在不同心率下的组织双轴粘弹性，将通过应力松弛和循环拉伸试验实验测量右心室的被动粘弹性，并使用我们验证的模型进行计算模拟。为了揭示细胞和细胞外组分对组织粘弹性的贡献，将进行药物治疗以使微管脱髓鞘并降解胶原蛋白，并量化组织粘弹性的变化。一个新的多尺度本构模型将被开发来预测肌纤维和胶原的粘弹性以及胶原的募集。最后，器官功能的变化将通过慢性高血压和急性应激改变的右心室粘弹性来测量。教育活动包括向北方科罗拉多的小学和初中到高中学生分发各种STEM工具包，参加校园内现有的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NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。