Document Detail

Silicon central pattern generators for cardiac diseases.
MedLine Citation:
PMID:  25433077     Owner:  NLM     Status:  Publisher    
Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronization but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat-to-beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPG) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPG). We discuss the limitations of present CPGs and appraise the advantages of analogue over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio-respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin-Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease. This article is protected by copyright. All rights reserved.
Alain Nogaret; Erin L O'Callaghan; Julian F R Paton; Renata M Lataro; Helio C Salgado; C Daniel Meliza; Edward Duncan; Henry D I Abarbanel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-28
Journal Detail:
Title:  The Journal of physiology     Volume:  -     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-29     Completed Date:  -     Revised Date:  2014-11-30    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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