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Device to Control and Monitor Cardiac Excitability


Stanford Reference:

11-259


Abstract


Stanford engineers have developed an all-electric pacing device that can stimulate or inhibit cardiac tissue while simultaneously recording its effects on the stimulated cells. This provides unprecedented ability to monitor the tissue in real-time, enabling detection of activity without blanking periods, and true closed-loop controlled stimulation. The device affords precise spatial and temporal control with beat-by-beat adjustments for improved safety and reliability. The technology is compatible with current stimulation delivery tools (microelectrode arrays, leads, catheters). Its applications include research, drug-screening, arrhythmia models, pacemaker devices and RF ablation guidance.

Stage of Research
-In vitro - in cardiomyocyte studies, the inventors used high-frequency stimulation and recorded depolarization events on the same electrode during the stimulus, enabling strength-duration relationship measurements and beat-to-beat stimulation threshold monitoring following pacing onset or pharmacological modulation. They also demonstrated the inhibition of excitation through prolonged high-frequency stimulation, and the generation of reversible conduction blocks.

-In vivo – the inventors are conducting studies of the device in large animal models.


Applications


  • In vitro electrophysiology - creation of reproducible conduction patterns for the study of cardiac conduction and cardiac arrhythmias (e.g., atrial fibrillation) in cultures, slices or explants
  • Cell-based drug screening assays - reproducible in vitro re-entry model for the identification of drugs affecting cardiac electrophysiology (e.g. modulating susceptibility to re-entry)
  • Pacemakers with in vivo closed-loop pacing - power optimized stimulation for pacemakers using measurement of tissue response to adjust stimulus in real-time, on a beat-by-beat basis
  • Radio-frequency ablation guidance - the impact of a conduction block under the catheter before permanently scaring the tissue

Advantages


  • Simultaneous stimulation and recording on the same electrode
  • Real-time feedback and monitoring:
    • for pacemaker applications – feedback on stimulation effectiveness
    • for drug screening applications – monitoring stimulation threshold changes such as modulation by pharmacological agents
  • Precise control - reversible, precise spatial and temporal control of conduction block (without alteration of the tissue or cellular structure)
  • Improved safety and reliability - lower electrode potentials reduces electrochemical reaction at electrodes, hence increases safety and reliability, especially for long-term use
  • Compatibility - all-electric technology compatible with standard electrophysiology delivery systems
  • Sustained conduction block - tested up to five minutes in cardiomyocyte cultures

Publications



Demonstration of Device on Cardiomyocyte Culture


Left: Illustration of high-frequency stimulation (a), and demonstration of simultaneous stimulation and recording of evoked depolarization of HL-1 cardiomyocytes, on the same electrode. Right: Calcium imaging of a depolarization wave in an HL-1 cardiomyocyte culture with an inhibitory stimulus applied to a ‘fence’ electrode (depicted by the dashed lines in the top panel): top – before application of the stimulus; middle – during inhibition; bottom – after the stimulus has been stopped. Note the wave wrapping around the inhibited block (and lack of depolarization inside), and the return to a normal propagation once the stimulus is stopped (adapted from Dura et al., PLoS ONE 7(4): e36217. doi:10.1371/journal.pone.0036217).

Real Time Video of Cardiomyocyte Excitability Inhibition


Innovators & Portfolio



Date Released

 9/10/2014
 

Licensing Contact


Mona Wan, Associate Director
650-498-0902 (Business)
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Related Keywords


cardiac pacing   atrial arrhythmia   Cardiac resynchronization   atrial fibrillation   arrhythmia   cardiac ablation   ablation   electrophysiology   MEMS: bioMEMS   microelectrode array   cardiac rhythm management   cardiac tissue   cardiovascular device   electrical stimulation   medical devices: cardiovascular   models of medical pathophysiology   screening: cellular assay   11-259   cardiomyocyte   catheter ablation   pacemakers   radiofrequency ablation   ventricular pacing   electrophysiologic monitoring   adaptive cardiac stimulation   defibrillator   
 

   

  

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