TISSUE CULTURE MODELS OF CARDIAC ARRHYTHMIAS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。折返性心律失常发生在多种情况下，经常危及心脏的血流动力学功能，有时导致晕厥或心源性猝死。这种节律通常非常复杂，包括阵发性发作和偏移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深入了解这些复杂动力学的起源。波的传播进行了监测，在单层鸡胚心脏细胞使用钙或电压荧光。当细胞培养成环状时，可以观察到复杂的阵发性节律，其中折返性兴奋自发地开始和停止。这是模拟的非线性方程，结合本地化的起搏器，显示减少兴奋性快速刺激。加入庚醇（一种降低细胞间电耦合的试剂）后，螺旋波分裂成多个较小的螺旋波。我们通过改变异构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。耦合的进一步减小导致所有传播的阻塞。我们也正在研究药物对自发振荡心脏细胞聚集体产生的节律的影响。这些药物的加入可能导致稳定的振荡节律转变为一种节律，其中有活动的爆发，随后是沉默期。我们感兴趣的可能性，这些突发的活动可能与阵发性心律失常中观察到的。

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.