TISSUE CULTURE MODELS OF CARDIAC ARRHYTHMIAS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。折返性心律失常发生在各种情况下，通常危及心脏的血液动力学功能，有时会导致晕厥或心脏性猝死。这种节律通常非常复杂，包括阵发性发作和抵消，以及不寻常的时间特征。我们使用心律失常的组织培养模型来洞察这些复杂动力学的起源。用钙或电压荧光监测鸡胚胎心肌细胞单层中的波传播。当细胞培养成环形时，可以观察到复杂的阵发性节律，在这种节律中，折返性兴奋自发地开始和停止。这是由包含局部起搏器的非线性方程模拟的，这些起搏器显示快速刺激后兴奋性降低。在加入庚醇后，螺旋波分解成多个更小的螺旋波。庚醇是一种减少细胞间电子耦合的试剂。我们通过改变异质元胞自动机模型中的耦合来对此进行建模。随着耦合范围的减小，波分裂成多个螺旋线。耦合的进一步降低会导致所有传播的阻塞。我们还在研究药物对自发振荡的心脏细胞聚集体产生的节律的影响。这些药物的加入可能会导致从稳定的振荡节奏转变为有突发活动，然后是静默的节奏。我们感兴趣的是，这些突发活动可能与在某些心律失常中观察到的阵发性节律有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Reentrant cardiac arrhythmias occur in a variety of circumstances, often jeopardizing hemodynamic function of the heart, and sometimes leading to syncope or sudden cardiac death. Such rhythms are often extremely complex, involving paroxysmal onset and offset and unusual temporal characteristics. We use tissue culture models of cardiac arrhythmia to gain insight into the origin of these complex dynamics. Wave propagation was monitored in monolayers of chick embryonic heart cells using calcium or voltage fluorescence. When cells are cultured in the shape of a ring, complex paroxysmal rhythms are observed in which reentrant excitation spontaneously starts and stops. This is modeled by nonlinear equations incorporating localized pacemakers that show reduced excitability following rapid stimulation. Following the addition of heptanol, an agent that reduces the electrical coupling between cells, spiral waves break up into multiple smaller spiral waves. We model this by changing the coupling in a heterogeneous cellular automaton model. As the range of coupling is decreased, waves break up into multiple spirals. Further decreases in coupling lead to block of all propagation. We are also studying the effects of pharmacologic agents on the rhythms generated by aggregates of spontaneously oscillating heart cells. Addition of these agents may lead to the transition of a stable oscillating rhythm to a rhythm in which there are bursts of activity, followed by periods of silence. We are interested in the possibility that these bursts of activity may be related to paroxysmal rhythms that are observed in some cardiac arrhythmias.