Reversible Cardiac Conduction Block and Defibrillation with High-Frequency Electric Field

Tandri, Harikrishna; Weinberg, Seth H.; Chang, Kelly C.; Zhu, Renjun; Trayanova, Natalia A.; Tung, Leslie; Berger, Ronald D.

doi:10.1126/scitranslmed.3002445

Cited by 42 publications

(37 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other work employing AC fields with similar frequency ranges also yielded induction of ventricular fibrillation (VF) [10], [13], continuous entrainment [14]–[16] and hemodynamic collapse [14]–[16] without observing any extended APD. In a concurrent study recently published, Tandri, et al have shown the ability of sinusoidal electric fields in the 20 Hz–2 kHz frequency range to produce reversible conduction blocks in several models (including monolayers and whole hearts) through inhibition of excitability by prolonged APD [9]. Using field stimulation of the whole culture or organ, complete conduction blocks were achieved for durations of up to one second.…”

Section: Introductionmentioning

confidence: 96%

Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation

Dura

Kovacs²,

Giovangrandi

2012

PLoS ONE

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 96%

Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation

Dura

Kovacs²,

Giovangrandi

2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…We have previously investigated alternating current as an alternative waveform to defibrillate, 27,28 but skeletal muscle activation was increased. We noted, however, that the longer duration of AC would allow skeletal muscle to be gradually tetanized before a standard biphasic shock.…”

Section: Discussionmentioning

confidence: 99%

Tetanizing prepulse: A novel strategy to mitigate implantable cardioverter-defibrillator shock-related pain

et al. 2016

Self Cite

View full text Add to dashboard Cite

Background Skeletal muscle activation has been implicated as the source of pain associated with ICD shocks. We hypothesized that the skeletal muscle response to defibrillatory shocks could be attenuated with a tetanizing pre-pulse immediately prior to biphasic shock delivery. Objectives The purpose of this study was to test the ability of tetanizing pre-pulses to reduce the skeletal muscle activation associated with defibrillation. Methods Seven adult pigs were studied. A left ventricular coil and subcutaneous dummy can in the right thorax were used to deliver either pure biphasic waveforms or test waveforms consisting of a tetanizing pulse of high-frequency alternating current (HFAC) ramped to an amplitude of 5–100 V over 0.25 to 1 s, immediately followed by a biphasic shock of approximately 9 J (ramped HFAC and biphasic, or rHFAC+B). We used limb acceleration and rate of force development (RoFD) as surrogate measures of pain. Test and control waveforms were delivered in sinus rhythm and induced VF to test defibrillation efficacy. Results Defibrillation threshold energy was indistinguishable between rHFAC+B and pure biphasic shocks. Peak acceleration and RoFD were reduced by 72%±7% and 71%±22%, respectively with a 25 V 1 s rHFAC+B waveform compared with pure biphasic shocks. Notably, rHFAC+B with a 9 J biphasic shock produced significantly less skeletal muscle activation than a 0.1J pure biphasic shock. Conclusion A putative source of ICD shock-related pain can be mitigated using a tetanizing pre-pulse followed by biphasic shock. Human studies will be required to assess true pain reduction with this approach.

show abstract

“…The study by Tandri et al [113] used sustained kilohertz-range alternating current (AC) fields for arrhythmia termination. Termination of arrhythmia with AC fields has been attempted previously in simulations [81][82][83] with limited success; the frequencies used in these studies were, however, substantially lower.…”

Section: Model-based Innovation To Improve Arrhythmia Termination By mentioning

confidence: 99%

Cardiac Arrhythmias: Mechanistic Knowledge and Innovation from Computer Models

Trayanova

Boyle

2015

MS&A

Self Cite

View full text Add to dashboard Cite

Computational simulation is increasingly recognized as an integral aspect of modern cardiovascular research. Realistic and biophysically detailed models of the cardio-circulatory system can help interpret complex experimental observations, dissect underlying mechanisms, and explain emerging organ-scale phenomena resulting from subtle changes at the tissue, cellular, and/or sub-cellular scales. This chapter provides an overview of recent advances in the simulation of cardiac electrical behavior, focusing specifically on detailed models of the initiation, perpetuation, and termination of ventricular arrhythmias, including fibrillation. The development and validation of such models has opened several noteworthy avenues of research, including close scrutiny of arrhythmia dynamics in healthy and diseased hearts, dissection of arrhythmogenic and cardioprotective properties of specialized cardiac tissue regions such as the Purkinje system, and exploration of emerging paradigms for anti-arrhythmia treatment, such as optogenetics. Excitingly, the clinical community is currently taking the first steps towards using patient-specific ventricular models to stratify arrhythmia risk, personalize treatment planning, and optimize device placement for difficult or unusual procedures.

show abstract

Reversible Cardiac Conduction Block and Defibrillation with High-Frequency Electric Field

Cited by 42 publications

References 40 publications

Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation

Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation

Tetanizing prepulse: A novel strategy to mitigate implantable cardioverter-defibrillator shock-related pain

Cardiac Arrhythmias: Mechanistic Knowledge and Innovation from Computer Models

Contact Info

Product

Resources

About