Mechanisms of triggered activity induction at the border zone of normal and abnormal cardiac tissue

Maldonado, Claudio; Li, Zhenyuan; Wead, William B.; Kupersmith, Joel

doi:10.1016/s0022-0736(96)80095-1

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…However, the distinction between these two terms has become less and less clear, as spontaneous triggered activity (leakiness of sarcoplasmic reticulum, Ca 21 overload, elevated I ns,Ca and I Cl(Na) , upregulation of Na 1 /Ca 21 exchanger, etc.) has been reported both experimentally (22)(23)(24) and theoretically (25). Thus, we refer to spontaneously active myocytes, regardless of underlying mechanism, as ectopic.…”

Section: Mechanisms Behind Automaticitymentioning

confidence: 86%

Genesis of Ectopic Waves: Role of Coupling, Automaticity, and Heterogeneity

Pumir¹,

Arutunyan

Krinsky³

et al. 2005

Biophysical Journal

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Many arrhythmias are believed to be triggered by ectopic sources arising from the border of the ischemic tissue. However, the development of ectopic activity from individual sources to a larger mass of cardiac tissue remains poorly understood. To address this critical issue, we used monolayers of neonatal rat cardiomyocytes to create conditions that promoted progression of ectopic activity from single cells to the network that consisted of hundreds of cells. To explain complex spatiotemporal patterns observed in these experiments we introduced a new theoretical framework. The framework's main feature is a parameter space diagram, which uses cell automaticity and coupling as two coordinates. The diagram allows one to depict network behavior, quantitatively address the heterogeneity factor, and evaluate transitions between different regimes. The well-organized wave trains were observed at moderate and high cell coupling values and network heterogeneity was found to be qualitatively unimportant for these regimes. In contrast, at lower values of coupling, spontaneous ectopic activity led to the appearance of fragmented ectopic waves. For these regimes, network heterogeneity played an essential role. The ectopic waves occasionally gave rise to spiral activity in two different regions within the parameter space via two distinct mechanisms. Together, our results suggest that localized ectopic waves represent an essential step in the progression of ectopic activity. These studies add to the understanding of initiation and progression of arrhythmias and can be applied to other phenomena that deal with assemblies of coupled oscillators.

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Section: Mechanisms Behind Automaticitymentioning

confidence: 86%

Genesis of Ectopic Waves: Role of Coupling, Automaticity, and Heterogeneity

Pumir¹,

Arutunyan

Krinsky³

et al. 2005

Biophysical Journal

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“…At present, the numerous investigations that address the mechanisms of ischemiareperfusion-induced arrhythmias fall into four major groups: 1) single cell studies (23,38); 2) mathematical modeling (1,31,33,41); 3) optical mapping or electrical recording of action potential propagation from the whole heart (19,24); and 4) use of cardiac fibers to address the origin of border zone arrhythmias (5,18). With the exception of the work by Kleber and colleagues (12,13,27) and the observation of spontaneous rotors in chick myocyte cultures (6), multicellular networks of cultured myocytes remain to be explored as a tool to address the origins of ischemia-reperfusion arrhythmias.…”

Section: Discussionmentioning

confidence: 99%

“…This, in turn, can be caused by a multitude of factors, including elevation of [Ca 2+ ] i and intracellular Na + concentration, decrease in the intracellular pH, depletion of ATP, and alterations in inward/outward currents, which bring the cell closer to its depolarization threshold (4,31). Similar factors increase the probability of either abnormal automaticity or triggered activity in ventricular and atrial cells (1,18,41). The ability of the method to identify ectopic loci can help to reveal the exact mechanisms of ectopic tachyarrhythmias because specific inhibitors can be readily included in ischemic or reperfusion solutions to test the contribution of the above factors.…”

Section: Discussionmentioning

confidence: 99%

Localized injury in cardiomyocyte network: a new experimental model of ischemia-reperfusion arrhythmias

Arutunyan¹,

Webster

Swift³

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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We developed a new experimental approach to study the effects of local injury in a multicellular preparation and tested the ability of the method to induce reperfusion arrhythmias in cardiomyocyte monolayers. A small region of injury was created using geometrically defined flows of control and ischemia-like solutions. Calcium transients were acquired simultaneously from injured, control, and border zone cells using fluo 4. Superfusion with the injury solution rapidly diminished the amplitude of calcium transients within the injury zone, followed by cessation of cell beating. Reperfusion caused an immediate tachyarrhythmic response in approximately 17% of experiments, with a wave front propagating from a single cell or small cell cluster within the former injury zone. Inclusion of a gap junction uncoupler (1 mM heptanol) in the injury solution narrowed the functional border and sharply increased the number of ectopic foci and the incidence of reperfusion arrhythmias. The model holds a potential to reveal both micro- and macroscopic features of propagation, conduction, and cell coupling in the normal and diseased myocardium and to serve as a new tool to test antiarrhythmic protocols in vitro.

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