Reentrant Activity in Cultured Cardiac Cell Monolayers
Reentrant Activity in Cultured Cardiac Cell Monolayers
批准号:
7822250
负责人:
LESLIE TUNG
金额:
$1.53万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-06-01 至 2010-10-31
关键词:
Adherent CultureAffectAleuritesAnisotropyArrhythmiaCalciumCalcium ChannelCalcium OscillationsCardiacCell Culture TechniquesCell modelCellsCellular MembraneCharacteristicsClassificationCoculture TechniquesCouplingCultured CellsDyesEvaluationExperimental ModelsFibroblastsGoalsHeart AtriumHeterogeneityIon ChannelIslandKnowledgeLengthLocationMapsMembraneMembrane PotentialsMyoblastsMyocardialNeonatalOpticsPathway interactionsPatternPlayPropertyRattusResearchResearch PersonnelResearch Project GrantsRoleSiteSkeletal MuscleSkeletal MyoblastsSpecific qualifier valueTachycardiaTestingThromboplastinTissue EngineeringTissuesVentricularWorkbasecell typegenetically engineered virusmonolayerprogramsregional differencevoltage
中文摘要
折返机制在许多类型的心律失常中起主要作用。功能性再入,在
螺旋波的形式,是许多心动过速以及纤颤的基础,但螺旋波的动力学特性
波浪稳定性和解体仍未得到很好的描述。我们实验室以前的工作已经证明
在培养的新生儿单层中可以诱导和系统地研究持续螺旋波活动
大鼠心肌细胞。这项工作的重点将是螺旋波的性质,特别是如何
受到组织异质性孤岛的影响,包括离子通道表达的改变,缝隙连接
耦合和异位病灶。将利用组织工程学方法来进行系统的评估
特定位置的不同类型的异质性。
我们建议使用电压和钙敏感染料和多点光学标测来追踪
心肌细胞单层的折返活动。我们将检验假设,(1)细胞的区域差异
膜特性可以锚定折返波并改变周期长度,(2)组织中的异质性
微结构导致不连续的传播并放大解剖障碍的锚定效应,
(3)再入过程中的块状线起源于微非均质,其长度受
兴奋性、波长和组织各向异性,(4)离子通道表达改变的孤岛可能足以
启动螺旋波分解,特别是在细胞-细胞耦合减少的条件下,以及(5)触发
活动和后去极化可导致螺旋波破裂,但需要临界质量和临界
耦合。这些目的是利用培养的细胞单层的特性作为一种控制良好的、多功能的
以及用于临床上重要的、基于折返性心律失常的基础研究的定量实验模型。
英文摘要
Reentrant mechanisms play a primary role in many types of cardiac arrhythmias. Functional reentry, in the
form of spiral waves, underlies many tachycardias as well as fibrillation, but the dynamic properties of spiral
wave stability and breakup are still not well characterized. Previous work from our lab has demonstrated that
sustained spiral wave activity can be induced and systematically studied in monolayers of cultured neonatal
rat ventricular cells. The focus of this work will be on the properties of spiral waves, and particularly how they
are influenced by islands of tissue heterogeneities that include altered ion channel expression, gap junctional
coupling, and ectopic foci. Tissue engineering approaches will be utilized to permit a systematic evaluation of
different types of heterogeneities at specified locations.
We propose to use voltage- and calcium-sensitive dyes and multi-site optical mapping to track the
reentrant activity in cardiac cell monolayers. We will test the hypotheses, (1) Regional differences in cellular
membrane properties can anchor reentrant waves and alter cycle length, (2) Heterogeneities in tissue
microstructure result in discontinous propagation and amplify the anchoring effects of anatomical obstacles,
(3) Lines of block during reentry originate from microheterogeneities, and their length is modulated by
excitability, wavelength and tissue anisotropy, (4) Islands of altered ion channel expression may suffice to
initiate spiral wave breakup, particularly under conditions of reduced cell-cell coupling, and (5) Triggered
activity and afterdepolarizations can cause spiral wave breakup but require critical mass and critical
coupling. These aims exploit the properties of the cultured cell monolayer as a well-controlled, versatile
and quantitative experimental model for basic studies of clinically important, reentry-based arrhythmias.
期刊论文(28)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
DOI:
10.1371/journal.pone.0040477
发表时间:
2012
期刊:
PloS one
影响因子:
3.7
作者:
[Weinberg SH, Tung L]
通讯作者:
Tung L
DOI:
10.1161/circresaha.108.176248
发表时间:
2009-11-20
期刊:
Circulation research
影响因子:
20.1
作者:
[Chang MG, Zhang Y, Chang CY, Xu L, Emokpae R, Tung L, Marbán E, Abraham MR]
通讯作者:
Abraham MR
DOI:
10.1016/j.yjmcc.2013.12.025
发表时间:
2014-03
期刊:
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
影响因子:
5
作者:
[Thompson, Susan A., Blazeski, Adriana, Copeland, Craig R., Cohen, Daniel M., Chen, Christopher S., Reich, Daniel M., Tung, Leslie]
通讯作者:
Tung, Leslie
DOI:
10.1007/s13239-010-0020-8
发表时间:
2010-09
期刊:
Cardiovascular engineering and technology
影响因子:
1.8
作者:
[Limpitikul W, Christoforou N, Thompson SA, Gearhart JD, Tung L, Lipke EA]
通讯作者:
Lipke EA
Myofibrillar architecture in engineered cardiac myocytes.
工程心肌细胞中的肌原纤维结构。
DOI:
10.1161/circresaha.108.182469
发表时间:
2008-08-15
期刊:
Circulation research
影响因子:
20.1
作者:
[Parker KK, Tan J, Chen CS, Tung L]
通讯作者:
Tung L
共 7 条
Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia
-
批准号:10593346
-
项目类别:
-
资助金额:$5.89万
-
财政年份:2020
-
负责人:LESLIE TUNG
-
依托单位:
Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia
-
批准号:10593334
-
项目类别:
-
资助金额:$4.65万
-
财政年份:2020
-
负责人:LESLIE TUNG
-
依托单位:
Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia
-
批准号:10250777
-
项目类别:
-
资助金额:$1.18万
-
财政年份:2020
-
负责人:LESLIE TUNG
-
依托单位:
Mechanoelectrical Interactions Between Cardiac Myofibroblasts and Myocytes
-
批准号:9204715
-
项目类别:
-
资助金额:$50.84万
-
财政年份:2016
-
负责人:LESLIE TUNG
-
依托单位:
ARVD/C Dysfunction in Human Stem Cell-Derived Cardiac Tissue
-
批准号:9815578
-
项目类别:
-
资助金额:$1.7万
-
财政年份:2016
-
负责人:LESLIE TUNG
-
依托单位:
ARVD/C Dysfunction in Human Stem Cell-Derived Cardiac Tissue
-
批准号:9106007
-
项目类别:
-
资助金额:$40.5万
-
财政年份:2016
-
负责人:LESLIE TUNG
-
依托单位:
Mechanoelectrical Interactions Between Cardiac Myofibroblasts and Myocytes
-
批准号:9028886
-
项目类别:
-
资助金额:$52.88万
-
财政年份:2016
-
负责人:LESLIE TUNG
-
依托单位:
ARVD/C Dysfunction in Human Stem Cell-Derived Cardiac Tissue
-
批准号:9251893
-
项目类别:
-
资助金额:$40.5万
-
财政年份:2016
-
负责人:LESLIE TUNG
-
依托单位:
Functional Classification of Cardiomyocytes Derived from Stem Cells
-
批准号:8095482
-
项目类别:
-
资助金额:$24.6万
-
财政年份:2011
-
负责人:LESLIE TUNG
-
依托单位:
Functional Classification of Cardiomyocytes Derived from Stem Cells
-
批准号:8259042
-
项目类别:
-
资助金额:$20.5万
-
财政年份:2011
-
负责人:LESLIE TUNG
-
依托单位:
JHU Ultima-L Imaging System
-
批准号:7595518
-
项目类别:
-
资助金额:$15.77万
-
财政年份:2009
-
负责人:LESLIE TUNG
-
依托单位:
Electrical Control of Reentrant Spiral Waves in Cardiac Tissue
-
批准号:7086735
-
项目类别:
-
资助金额:$24.51万
-
财政年份:2006
-
负责人:LESLIE TUNG
-
依托单位:
Electrical Control of Reentrant Spiral Waves in Cardiac Tissue
-
批准号:7230157
-
项目类别:
-
资助金额:$19.89万
-
财政年份:2006
-
负责人:LESLIE TUNG
-
依托单位:
Contact Fluorescence Imaging
-
批准号:6918520
-
项目类别:
-
资助金额:$20.44万
-
财政年份:2004
-
负责人:LESLIE TUNG
-
依托单位:
Contact Fluorescence Imaging
-
批准号:6775178
-
项目类别:
-
资助金额:$20.44万
-
财政年份:2004
-
负责人:LESLIE TUNG
-
依托单位:
Contact Fluorescence Imaging
-
批准号:7090741
-
项目类别:
-
资助金额:$19.96万
-
财政年份:2004
-
负责人:LESLIE TUNG
-
依托单位:
Bioreactor for Stem Cell Tissue Engineering
-
批准号:6443230
-
项目类别:
-
资助金额:$10.4万
-
财政年份:2002
-
负责人:LESLIE TUNG
-
依托单位:
REENTRANT ACTIVITY IN CULTURED CARDIAC CELL MONOLAYERS
-
批准号:6558853
-
项目类别:
-
资助金额:$6.13万
-
财政年份:2001
-
负责人:LESLIE TUNG
-
依托单位:
Reentrant Activity in Cultured Cardiac Cell Monolayers
-
批准号:7568165
-
项目类别:
-
资助金额:$39.81万
-
财政年份:2001
-
负责人:LESLIE TUNG
-
依托单位:
Reentrant Activity in Cultured Cardiac Cell Monolayers
-
批准号:7185808
-
项目类别:
-
资助金额:$39.74万
-
财政年份:2001
-
负责人:LESLIE TUNG
-
依托单位:
海外基金