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.

右心室的失败可能表明诸如肺动高压和心力衰竭的疾病中死亡的风险更高，并保留了射血分数。患有这些疾病的人经常报告运动肠，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机械行为及其如何影响其抽水功能的理解。粘弹性的概念是指在收缩和放松期间心脏组织的直接（弹性）和延迟（粘性）耐药性，将用于研究细胞行为和心脏的整体表现如何受到影响。该研究将包括对右通气组织的粘弹性及其对器官功能的影响的全面分析。这项研究的发现可用于大约670万心力衰竭患者的护理和管理，这些患者预计随着老龄化的人口而增加。研究团队计划吸引年轻人的思想并推进下一代生物工程师的教育，重点是使妇女和第一代学生进行心理化，以增强STEM劳动力的多样性。该研究的目的是发现通风壁粘弹性特性在急性压力下如何变化，并在急性肺部高血压和持续性高血压和影响器官功能下发生变化。为了表征通过疾病进展和心率变化的组织双轴粘弹性，右通气的被动粘弹性将通过应力放松和周期性拉伸测试进行实验测量，并通过我们经过验证的模型在计算上进行计算。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蛋白，并将量化组织粘弹性的变化。将开发一个新的多尺度组成模型，以预测肌纤维和胶原蛋白以及胶原蛋白招募的粘弹性。最后，将通过透镜高血压和急性应激改变的右通气粘弹性来测量器官功能变化。教育活动包括在科罗拉多州北部的小学和中学学生分发各种STEM套件，参加校园现有的K-12公共外展活动。此外，该奖项反映了NSF的法定任务，并通过基金会的知识分子优点和更广泛的影响评估标准来反映NSF的法定任务。