Silicon central pattern generators for cardiac diseases

Alain Nogaret, Erin L. O'Callaghan, Renata M. Lataro, Helio C. Salgado, C. Daniel Meliza, Edward Duncan, Henry D. I. Abarbanel, Julian F. R. Paton

Research output: Contribution to journalArticle

7 Citations (Scopus)
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Abstract

Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronisation 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 (hCPGs) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPGs). We discuss the limitations of present CPGs and appraise the advantages of analog 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.

Original languageEnglish
Pages (from-to)763-774
Number of pages12
JournalJournal of Physiology
Volume593
Issue number4
Early online date5 Jan 2015
DOIs
Publication statusPublished - 15 Feb 2015

Fingerprint

Central Pattern Generators
Silicon
Heart Diseases
Physiological Feedback
Vagus Nerve
Respiration
Heart Rate
Biophysics
Neurons
Medulla Oblongata
Electromyography
Therapeutic Uses
Respiratory Rate
Synapses
Cardiac Arrhythmias
Heart Failure
Medicine
Technology
Equipment and Supplies
Respiratory Sinus Arrhythmia

Cite this

Nogaret, A., O'Callaghan, E. L., Lataro, R. M., Salgado, H. C., Meliza, C. D., Duncan, E., ... Paton, J. F. R. (2015). Silicon central pattern generators for cardiac diseases. Journal of Physiology, 593(4), 763-774. https://doi.org/10.1113/jphysiol.2014.282723

Silicon central pattern generators for cardiac diseases. / Nogaret, Alain; O'Callaghan, Erin L.; Lataro, Renata M.; Salgado, Helio C.; Meliza, C. Daniel; Duncan, Edward; Abarbanel, Henry D. I.; Paton, Julian F. R.

In: Journal of Physiology, Vol. 593, No. 4, 15.02.2015, p. 763-774.

Research output: Contribution to journalArticle

Nogaret, A, O'Callaghan, EL, Lataro, RM, Salgado, HC, Meliza, CD, Duncan, E, Abarbanel, HDI & Paton, JFR 2015, 'Silicon central pattern generators for cardiac diseases', Journal of Physiology, vol. 593, no. 4, pp. 763-774. https://doi.org/10.1113/jphysiol.2014.282723
Nogaret A, O'Callaghan EL, Lataro RM, Salgado HC, Meliza CD, Duncan E et al. Silicon central pattern generators for cardiac diseases. Journal of Physiology. 2015 Feb 15;593(4):763-774. https://doi.org/10.1113/jphysiol.2014.282723
Nogaret, Alain ; O'Callaghan, Erin L. ; Lataro, Renata M. ; Salgado, Helio C. ; Meliza, C. Daniel ; Duncan, Edward ; Abarbanel, Henry D. I. ; Paton, Julian F. R. / Silicon central pattern generators for cardiac diseases. In: Journal of Physiology. 2015 ; Vol. 593, No. 4. pp. 763-774.
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