TISSUE CULTURE MODELS OF CARDIAC ARRHYTHMIAS

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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.