Impact of Blood Viscosity and Vascular Compliance on Fontan Circulation Dysfunction in Children
血液粘度和血管顺应性对儿童Fontan循环障碍的影响
基本信息
- 批准号:10350382
- 负责人:
- 金额:$ 16.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-01 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:4D MRIAccountingAffectBehaviorBiomechanicsBloodBlood CirculationBlood VesselsBlood ViscosityBlood flowCaliforniaCardiacCardiac Catheterization ProceduresCardiac OutputCardiopulmonaryCaringCessation of lifeChildChildhoodChronically IllClinicalClinical MarkersComplexComputer ModelsCongenital Heart DefectsCyanosisDataDevelopmentDevelopment PlansDiagnosisEducational CurriculumElectrical EngineeringEngineeringExerciseExercise TestFaceFailureFunctional disorderFundingGeometryGoalsHeartHeart DiseasesHeart TransplantationIn VitroInterdisciplinary StudyLiquid substanceLiver FailureLos AngelesLungLymphaticMagnetic Resonance ImagingMentored Patient-Oriented Research Career Development AwardMissionModelingNational Heart, Lung, and Blood InstituteOperative Surgical ProceduresOrganOutcomePatientsPediatric HospitalsPediatric cardiologyPediatric cohortPerformancePersonsPharmacologyPhysiciansPhysiologic pulsePopulationPredictive ValuePreventionPrognostic MarkerPropertyPublic HealthPublishingPulmonary artery structureResearchResearch DesignResearch PersonnelResearch Project GrantsRestRiskRoleScientistSingle ventricle congenital heart diseaseTestingTherapeutic InterventionTrainingTranslatingUniversitiesVariantVascular DiseasesVenousVentricular DysfunctionViscosityWisconsinagedbasecardiac magnetic resonance imagingcareer developmentcohortcongenital heart disorderethnic diversityexercise capacityexperienceimprovedin vivomortalitymultidisciplinarynovelprematurepreventshear stressstatisticstool
项目摘要
PROJECT SUMMARY/ABSTRACT
The Fontan surgical procedure has greatly improved survival in children born with univentricular congenital heart
defects. Unfortunately, most will develop multiorgan dysfunction, and all face a progressively increasing risk of
Fontan failure and premature death. Due to an incomplete understanding of the pathophysiology, Fontan failure
remains difficult to predict and treat. While the surgery creates the same fundamentally abnormal circulation and
vascular dysfunction in all patients by redirecting low-shear systemic venous blood from the heart to the lungs,
the variability in timing and presentation of Fontan failure is unexplained. Computational fluid dynamic (CFD)
modeling has been used to demonstrate that power loss across the Fontan conduit and pulmonary vasculature
is a significant but incomplete determinant of circulation performance. Although power loss is due to viscous
energy loss from shear forces in blood, prior studies have overlooked several important features of blood
viscosity, most notably its property of increasing exponentially at low shear rates (“non-Newtonian behavior”
[NNB]), such as in the Fontan circulation. The objectives of this project are to (i) elucidate the extent to which
NNB affects Fontan circulation performance in vivo; and (ii) correlate performance metrics with clinical markers
of Fontan failure. Based on published and preliminary in vitro observations, the central hypothesis is that patient-
specific variation in the NNB of blood, modulated by vascular compliance and cardiac output, determines Fontan
circulatory performance and clinical outcomes. The rationale for this proposal is that characterization of the role
of non-Newtonian viscosity in Fontan circulation pathophysiology will serve as a framework for developing
sensitive tools to screen for Fontan failure and pharmacologic therapies to prevent Fontan failure. This proposal
will harness the strengths of a multidisciplinary team from Children’s Hospital Los Angeles, University of
Southern California, University of California - Irvine, and University of Wisconsin. Using a combination of CFD
modeling, 4D flow magnetic resonance imaging, blood viscosity analysis, and exercise testing to study an
ethnically diverse cross-sectional cohort of pediatric Fontan patients, the central hypothesis will be tested by
pursuing these specific aims: (1) Determine the extent to which patient-specific differences in NNB explain
variability in Fontan circulation performance; (2) Determine the extent to which regional vascular compliance
modulates NNB; and (3) Determine the predictive value of non-Newtonian power loss on exercise capacity. The
K23 mechanism will allow the PI to complete a robust career development plan including formalized curricula in
study design, statistics, and engineering, and hands-on training in CFD modeling and 4D flow MRI. Together,
the research plan and career development activities will support the PI’s long-term goal of becoming an
independently funded physician-scientist, focusing on studying vascular biomechanics in children with congenital
heart disease in order to improve the diagnosis and management of cardiac decompensation.
项目概要/摘要
Fontan 手术极大地提高了单心室先天性心脏病儿童的生存率
缺陷。不幸的是,大多数人都会出现多器官功能障碍,并且所有人都面临着逐渐增加的风险
Fontan 衰竭和过早死亡。由于对病理生理学的不完全了解,Fontan 失败
仍然难以预测和治疗。虽然手术造成了同样的根本性异常循环和
通过将低剪切全身静脉血从心脏重新引导至肺部来治疗所有患者的血管功能障碍,
Fontan 衰竭的时间和表现的变化无法解释。计算流体动力学 (CFD)
模型已用于证明 Fontan 导管和肺脉管系统的功率损失
是循环性能的重要但不完整的决定因素。虽然功率损失是由于粘性造成的
由于血液中剪切力造成的能量损失,先前的研究忽略了血液的几个重要特征
粘度,最显着的是其在低剪切速率下呈指数增加的特性(“非牛顿行为”
[NNB]),例如在 Fontan 循环中。该项目的目标是 (i) 阐明在多大程度上
NNB影响体内Fontan循环性能; (ii) 将表现指标与临床标志物相关联
Fontan 失败。根据已发表的和初步的体外观察,中心假设是患者
血液 NNB 的特定变化由血管顺应性和心输出量调节,决定了 Fontan
循环性能和临床结果。该提案的基本原理是角色的特征
Fontan 循环病理生理学中非牛顿粘度的研究将作为开发框架
筛选 Fontan 失败的敏感工具和预防 Fontan 失败的药物疗法。这个提议
将利用洛杉矶大学儿童医院多学科团队的优势
南加州大学、加州大学欧文分校和威斯康星大学。结合使用 CFD
建模、4D 血流磁共振成像、血液粘度分析和运动测试来研究
种族多样化的儿童 Fontan 患者横断面队列,中心假设将通过
追求这些具体目标:(1) 确定 NNB 中患者特异性差异的解释程度
Fontan 循环性能的可变性; (2)确定局部血管顺应性的程度
调节 NNB; (3)确定非牛顿功率损失对运动能力的预测价值。这
K23机制将允许PI完成稳健的职业发展计划,包括正式课程
研究设计、统计学和工程,以及 CFD 建模和 4D 流 MRI 方面的实践培训。一起,
研究计划和职业发展活动将支持 PI 成为一名
独立资助的医师科学家,专注于研究先天性儿童血管生物力学
心脏病,以改善心脏失代偿的诊断和治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Andrew L Cheng其他文献
Comparison of MOLLI and ShMOLLI at 1.5 and 3 Tesla for detection of early cardiac iron deposition in patients with transfusional siderosis
- DOI:
10.1186/1532-429x-18-s1-p123 - 发表时间:
2016-01-27 - 期刊:
- 影响因子:
- 作者:
Andrew L Cheng;John Wood - 通讯作者:
John Wood
Andrew L Cheng的其他文献
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{{ truncateString('Andrew L Cheng', 18)}}的其他基金
Impact of Blood Viscosity and Vascular Compliance on Fontan Circulation Dysfunction in Children
血液粘度和血管顺应性对儿童Fontan循环障碍的影响
- 批准号:
10579966 - 财政年份:2022
- 资助金额:
$ 16.98万 - 项目类别:
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