Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation
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Mendeley | Further Information

{"title"=>"Spatiotemporally controlled cardiac conduction block using high-frequency electrical stimulation.", "type"=>"journal", "authors"=>[{"first_name"=>"Burak", "last_name"=>"Dura"}, {"first_name"=>"Gregory T a", "last_name"=>"Kovacs"}, {"first_name"=>"Laurent", "last_name"=>"Giovangrandi"}], "year"=>2012, "source"=>"PloS one", "identifiers"=>{"issn"=>"1932-6203", "pmid"=>"22558389", "doi"=>"10.1371/journal.pone.0036217"}, "keywords"=>["Action Potentials", "Animals", "Cardiac", "Cardiac: cytology", "Cell Line", "Electric Stimulation", "Electric Stimulation: instrumentation", "Electric Stimulation: methods", "Electrodes", "Extracellular Space", "Extracellular Space: metabolism", "Heart Conduction System", "Heart Conduction System: cytology", "Mice", "Myocytes", "Time Factors"], "id"=>"b8715958-2c2c-319b-9f79-56ec216ee030", "abstract"=>"BACKGROUND: Methods 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.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: We 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).\\n\\nCONCLUSION/SIGNIFICANCE: Inhibition 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.", "link"=>"http://www.mendeley.com/research/spatiotemporally-controlled-cardiac-conduction-block-using-highfrequency-electrical-stimulation-1", "reader_count"=>28, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>10, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>6}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>10, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>6}, "reader_count_by_subject_area"=>{"Engineering"=>8, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>13, "Medicine and Dentistry"=>3, "Neuroscience"=>1, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>8}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"Hungary"=>1, "United States"=>2, "Russia"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/645276"], "description"=>"<p>A. Microelectrode array used in the experiment. Yellow arrows labeled 1 and 2 represent the conduction paths before and during the block, as derived from the isochrone maps in (C). SE, stimulation electrode used for pacing cells; BE, blocking electrode; RE, recording electrodes. B. Electrical recordings showing the change in conduction path during blocking by the increased time delay between stimulation pulse and LATs. Black bar represents the block duration. (* denotes one missed beat during the experiment). C. Isochrone maps revealing the direction change in conduction path.</p>", "links"=>[], "tags"=>["conduction", "high-frequency", "suprathreshold", "ac"], "article_id"=>315768, "categories"=>["Physiology", "Biotechnology"], "users"=>["Burak Dura", "Gregory T. A. Kovacs", "Laurent Giovangrandi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036217.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Guidance_of_conduction_path_using_high_frequency_suprathreshold_AC_stimuli_/315768", "title"=>"Guidance of conduction path using high-frequency suprathreshold AC stimuli.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:36:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/645380"], "description"=>"<p>A–E. Prolonged action potential. Simulated responses to 1 kHz square wave applied between <i>t</i> = 10 ms and <i>t</i> = 510 ms. Prolonged action potential revealed by membrane potential (A, F) and intracellular Ca<sup>2+</sup> levels (B, G). C. Inactivation of Na<sup>+</sup> channels (during the block, fast and slow inactivation gating parameters – <i>h</i><sub>1</sub> and <i>h</i><sub>2</sub> – decreased to zero; activation gating variable <i>m</i> oscillated between 0 and 1 in comparison to resting values in H). D. Prolonged activation of inward Ca<sup>2+</sup> channel (during the block, fast and slow inactivation gating parameters – <i>f</i><sub>L1</sub> and <i>f</i><sub>L2</sub> – remained lowered while activation gating variable <i>d</i><sub>L</sub> remained high compared to resting values in I). E. Prolonged activation of outward K<sup>+</sup> channel (during the block, inactivation gating variable <i>s</i><sub>SUS</sub> lowered to 0.9 while activation gating variable <i>r</i><sub>SUS</sub> plateaued around 0.3 in comparison with resting values in J). F–J. Normal action potential. Simulated responses to a stimulus of 10 ms duration applied at <i>t</i> = 40 ms.</p>", "links"=>[], "tags"=>["simulation", "suprathreshold", "ac", "inhibition", "compared"], "article_id"=>315874, "categories"=>["Physiology", "Biotechnology"], "users"=>["Burak Dura", "Gregory T. A. Kovacs", "Laurent Giovangrandi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036217.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Single_cell_simulation_results_of_suprathreshold_AC_inhibition_compared_to_normal_action_potential_/315874", "title"=>"Single-cell simulation results of suprathreshold AC inhibition compared to normal action potential.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:37:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/645160"], "description"=>"<p>Time-lapse of Ca<sup>2+</sup> fluorescence showing propagation of electrical activity before, during and after application of the inhibitory stimulus. White dotted lines highlight the location and geometry of blocking electrode (electrode A in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036217#pone-0036217-g001\" target=\"_blank\">Fig. 1A,D</a>). Red indicates high Ca<sup>2+</sup> concentration, blue low.</p>", "links"=>[], "tags"=>["spatiotemporally", "controlled", "conduction"], "article_id"=>315651, "categories"=>["Physiology", "Biotechnology"], "users"=>["Burak Dura", "Gregory T. A. Kovacs", "Laurent Giovangrandi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036217.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demonstration_of_spatiotemporally_controlled_electrical_conduction_block_50_A_p_p_5_kHz_/315651", "title"=>"Demonstration of spatiotemporally controlled electrical conduction block (50 µA<sub>p-p</sub>, 5 kHz).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:34:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/645033"], "description"=>"<p>A. Microelectrode array. Scale bar, 500 µm. B. Relationship between blocking threshold and frequency. C. Close-up (based on B) of the cell response to low frequency AC stimuli, highlighting the region of entrainment (multiple APs) before full response is reached. The dotted line is extrapolated. D. Left, representation of blocking electrode A with regions of interest (ROIs) for Ca<sup>2+</sup> imaging. Right, example of Ca<sup>2+</sup> recordings from ROIs during blocking experiments. Arrows point to the action potential generated at onset of inhibition stimulus. Black bar represents the inhibition duration. E. Repolarization analysis indicating prolonged action potentials for inhibited cells. Repolarizations are normalized with respect to standard repolarization during regular action potentials. (Error bars, s.d.; <i>n</i> = 9 cultures; *** indicates <i>p</i><0.001; ** indicates <i>p</i><0.01). F. Comparison of inhibition thresholds (peak-to-peak) between sinusoidal and square waveforms. (B, C and F: error bars, s.d.; <i>n</i> = 6 cultures; µA, microamperes; * indicates <i>p</i><0.05; ** indicates <i>p</i><0.01; *** indicates <i>p</i><0.001.).</p>", "links"=>[], "tags"=>["suprathreshold", "ac", "inhibition", "conduction"], "article_id"=>315526, "categories"=>["Physiology", "Biotechnology"], "users"=>["Burak Dura", "Gregory T. A. Kovacs", "Laurent Giovangrandi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036217.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_suprathreshold_AC_inhibition_and_conduction_block_/315526", "title"=>"Characterization of suprathreshold AC inhibition and conduction block.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-04-30 01:32:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/332526", "https://ndownloader.figshare.com/files/332579", "https://ndownloader.figshare.com/files/332630", "https://ndownloader.figshare.com/files/332697", "https://ndownloader.figshare.com/files/332775", "https://ndownloader.figshare.com/files/332862", "https://ndownloader.figshare.com/files/332901", "https://ndownloader.figshare.com/files/332951"], "description"=>"<div><h3>Background</h3><p>Methods 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 <em>in vivo</em>. Therefore, an inhibition method that does not lead to entrainment – irrespective of the stimulation amplitude (bound to fluctuate in an <em>in vivo</em> setting) – is highly desirable.</p> <h3>Methodology/Principal Findings</h3><p>We 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).</p> <h3>Conclusion/Significance</h3><p>Inhibition 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 <em>in vitro</em>, as well as safer and more efficacious tools for <em>in vivo</em> cardiac mapping and radio-frequency ablation guidance applications.</p> </div>", "links"=>[], "tags"=>["spatiotemporally", "controlled", "cardiac", "conduction", "high-frequency", "stimulation"], "article_id"=>125654, "categories"=>["Physiology", "Biotechnology"], "users"=>["Burak Dura", "Gregory T. A. Kovacs", "Laurent Giovangrandi"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0036217.s001", "https://dx.doi.org/10.1371/journal.pone.0036217.s002", "https://dx.doi.org/10.1371/journal.pone.0036217.s003", "https://dx.doi.org/10.1371/journal.pone.0036217.s004", "https://dx.doi.org/10.1371/journal.pone.0036217.s005", "https://dx.doi.org/10.1371/journal.pone.0036217.s006", "https://dx.doi.org/10.1371/journal.pone.0036217.s007", "https://dx.doi.org/10.1371/journal.pone.0036217.s008"], "stats"=>{"downloads"=>25, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Spatiotemporally_Controlled_Cardiac_Conduction_Block_Using_High_Frequency_Electrical_Stimulation/125654", "title"=>"Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-04-30 01:34:14"}

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Relative Metric

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