Reentrant waves in a ring of embryonic chick ventricular cells imaged with a Ca2+ sensitive dye

González, Hortensia; Nagai, Yoshihiko; Bub, Gil; Glass, Leon; Shrier, Alvin

doi:10.1016/s0303-2647(03)00111-4

Cited by 25 publications

(17 citation statements)

References 26 publications

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“…Traditional techniques usually require permanent, physical patterning of the cells, through surface modification [28] or physical constrains [29]. In contrast, this method induces reversible, reconfigurable blocks without any particular tissue preparation.…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation

Dura

Kovacs²,

Giovangrandi

2012

PLoS ONE

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BackgroundMethods for the electrical inhibition of cardiac excitation have long been sought to control excitability and conduction, but to date remain largely impractical. High-amplitude alternating current (AC) stimulation has been known to extend cardiac action potentials (APs), and has been recently exploited to terminate reentrant arrhythmias by producing reversible conduction blocks. Yet, low-amplitude currents at similar frequencies have been shown to entrain cardiac tissues by generation of repetitive APs, leading in some cases to ventricular fibrillation and hemodynamic collapse in vivo. Therefore, an inhibition method that does not lead to entrainment – irrespective of the stimulation amplitude (bound to fluctuate in an in vivo setting) – is highly desirable.Methodology/Principal FindingsWe investigated the effects of broader amplitude and frequency ranges on the inhibitory effects of extracellular AC stimulation on HL-1 cardiomyocytes cultured on microelectrode arrays, using both sinusoidal and square waveforms. Our results indicate that, at sufficiently high frequencies, cardiac tissue exhibits a binary response to stimulus amplitude with either prolonged APs or no effect, thereby effectively avoiding the risks of entrainment by repetitive firing observed at lower frequencies. We further demonstrate the ability to precisely define reversible local conduction blocks in beating cultures without influencing the propagation activity in non-blocked areas. The conduction blocks were spatiotemporally controlled by electrode geometry and stimuli duration, respectively, and sustainable for long durations (300 s).Conclusion/SignificanceInhibition of cardiac excitation induced by high-frequency AC stimulation exhibits a binary response to amplitude above a threshold frequency, enabling the generation of reversible conduction blocks without the risks of entrainment. This inhibition method could yield novel approaches for arrhythmia modeling in vitro, as well as safer and more efficacious tools for in vivo cardiac mapping and radio-frequency ablation guidance applications.

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Section: Discussionmentioning

confidence: 99%

Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation

Dura

Kovacs²,

Giovangrandi

2012

PLoS ONE

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“…On the other hand, spiral waves [re-entrant waves (ReWs)] within cardiac tissue have long been investigated as a model for arrhythmia studies [27][28][29][30][31] , and the rapid beating caused by in vivo spiral wave could lead to dysfunction of heart and even death of a patient. However, when used in an in vitro condition, the rapid beating caused by spiral wave, similar to rapid electrical stimulation 14 , could be beneficial for cardiomyocytes' maturation.…”

mentioning

confidence: 99%

Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring

Zhang

et al. 2020

Commun Biol

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Directed differentiation methods allow acquisition of high-purity cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs); however, their immaturity characteristic limits their application for drug screening and regenerative therapy. The rapid electrical pacing of cardiomyocytes has been used for efficiently promoting the maturation of cardiomyocytes, here we describe a simple device in modified culture plate on which hiPSCderived cardiomyocytes can form three-dimensional self-organized tissue rings (SOTRs). Using calcium imaging, we show that within the ring, reentrant waves (ReWs) of action potential spontaneously originated and ran robustly at a frequency up to 4 Hz. After 2 weeks, SOTRs with ReWs show higher maturation including structural organization, increased cardiac-specific gene expression, enhanced Ca 2+-handling properties, an increased oxygenconsumption rate, and enhanced contractile force. We subsequently use a mathematical model to interpret the origination, propagation, and long-term behavior of the ReWs within the SOTRs.

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“…In Mines' circus movement model, an extrastimulus can have one of three effects on reentry: (A) leave the reentry unaffected, (B) terminate the reentry or (C) reset the reentry, depending on the phase of the extrastimulus relative to the reentry cycle and excitable gap ( Fig. 2) (Glass & Josephson, 1995;Waldo, 1997;Gonzalez et al 2003). Resetting of a reentrant arrhythmia ( Fig.…”

Section: Manipulating Reentry: Resetting Entrainment and Anti-tachycmentioning

confidence: 99%

The pioneering work of George Mines on cardiac arrhythmias: groundbreaking ideas that remain influential in contemporary cardiac electrophysiology

Aguilar

Nattel

2016

The Journal of Physiology

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George Mines was a pioneering physiologist who, despite an extremely short period of professional activity and only primitive experimental methodology, succeeded in formulating concepts that continue to be of great influence today. Here, we review some of his most important discoveries and their impact on contemporary concepts and clinical practice. Mines' greatest contribution was his conceptualization and characterization of circus movement reentry. His observations and ideas about the basis for cardiac reentrant activity underlie how we understand and manage a wide range of important clinical rhythm disturbances today. The notions he introduced regarding the influence of premature extrastimuli on reentry (termination, resetting and entrainment) are central to contemporary assessment of arrhythmia mechanisms in clinical electrophysiology laboratories and modern device therapy of cardiac tachyarrhythmias. Refinements of his model of reentry have led to sophisticated biophysical theories of the mechanisms underlying cardiac fibrillation. His seminal observations on the influence of electrolyte derangements and autonomic tone on the heart are relevant to our understanding of the physiology and pharmacology of arrhythmias caused by cardiac pathology. In this era of advanced technology, it is important to appreciate that ideas of lasting impact come from great minds and do not necessarily require great tools.(Received 22 July 2015; accepted after revision 9 September 2015; first published online 26 November 2015) Corresponding author S. Nattel: 5000 Belanger St. E, Montreal, Quebec, Canada H1T 1C8. Email: stanley.nattel@icm-mhi.org Abstract figure legend Mine's major contribution to the field of cardiac electrophysiology was the notion of circus movement reentry, a concept with far-reaching theoretical and clinical applications that remains highly relevant in modern electrophysiology. His model of cardiac fibrillation based on circus movement reentry paved the way for modern theories of fibrillation such as leading circle and spiral wave reentry. Mines was also instrumental in developing the notion of the vulnerable period of the cardiac cycle, the time window during which an extra-stimulus can trigger fibrillation, which forms the basis of several practical applications (e.g., synchronized cardioversion and pacemaker sensing function). Other noteworthy contributions include the description of the effects of metabolic abnormalities and vagal nerve stimulation on the electrocardiogram. Presently-used practical clinical applications resulting from Mines' discoveries are shown in the grey boxes.

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Reentrant waves in a ring of embryonic chick ventricular cells imaged with a Ca2+ sensitive dye

Cited by 25 publications

References 26 publications

Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation

Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation

Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring

The pioneering work of George Mines on cardiac arrhythmias: groundbreaking ideas that remain influential in contemporary cardiac electrophysiology

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