{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:54:29Z","timestamp":1790949269907,"version":"4.1.0"},"reference-count":90,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,1,5]],"date-time":"2015-01-05T00:00:00Z","timestamp":1420416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,2,15]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>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\u2010to\u2010beat 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\u2010respiratory 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\u2013Huxley 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.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.282723","type":"journal-article","created":{"date-parts":[[2014,11,29]],"date-time":"2014-11-29T03:39:55Z","timestamp":1417232395000},"page":"763-774","source":"Crossref","is-referenced-by-count":19,"title":["Silicon central pattern generators for cardiac diseases"],"prefix":"10.1113","volume":"593","author":[{"given":"Alain","family":"Nogaret","sequence":"first","affiliation":[{"name":"Department of Physics University of Bath  Bath BA2 7AY UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin L.","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"School of Physiology and Pharmacology Bristol CardioVascular University of Bristol  Bristol BS8 1TD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata M.","family":"Lataro","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helio C.","family":"Salgado","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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