Multi-nodal nano-actuator pacemaker for energy-efficient stimulation of cardiomyocytes

Abstract There is continuous interest in maximizing the longevity of implantable pacemakers, which are effective in remedying and managing patients with arrhythmic heart disease. This paper accordingly first proposes miniature actuating nanomachines that inter-connect with individual cardiomyocytes and then deeply explores their energy expenditure when performing basic cardiomyocyte stimulation tasks. Since evoked electrical impulses from a number of actuated cardiomyocytes could coordinate contraction throughout the remaining heart muscle and lead to a heart beat, the miniature actuating nanomachines acting synchronously form a conceptual multi-nodal nano-actuator pacemaker network. Rectangular-, sine-, half-sine-, and sawtooth stimulation pulses with varying configurations are considered for actuation of a single isolated in-silico cardiomyocyte by each of the nanomachines. Computer optimization methods with energy consumption as a cost function are utilized to configure preferable stimulation signals in terms of numbers of stimulation sessions/pulses, pulse amplitudes, and duration. In addition, the simulation data are compared with experimental data obtained using in-vitro mouse cardiomyocytes. Among the considered waveforms, half-sine pulses that lead to actuation of a single cardiomyocyte consume minimum energy. None of the used sequences with multiple stimulation pulses reduces the overall energy expenditure of cell stimulation when compared to a single pulse stimulation.

[1]  J. C. Norman,et al.  Surgical Treatment of Adams‐Stokes Syndrome Using Long‐term Inductive Coupled Coil Pacemaking: Experience with 30 Patients , 1964, Annals of surgery.

[2]  Kaushik Roy,et al.  Efficient Design of Micro-Scale Energy Harvesting Systems , 2011, IEEE Journal on Emerging and Selected Topics in Circuits and Systems.

[3]  R LIGHTWOOD,et al.  A surgical approach to the management of heart-block using an inductive coupled artifical cardiac pacemaker. , 1960, Lancet.

[4]  W G Holcomb,et al.  Cardiac pacemakers: Principles and practices , 1967 .

[5]  J W Moore,et al.  A numerical method to model excitable cells. , 1978, Biophysical journal.

[6]  Anagnostopoulos Ce,et al.  Electronic pacemakers of the heart, gastrointestinal tract, phrenic nerve, bladder, and carotid sinus: current status. , 1966 .

[7]  Elizabeth Cherry,et al.  Models of cardiac cell , 2008, Scholarpedia.

[8]  Charles R. Martin,et al.  FABRICATION AND EVALUATION OF NANOELECTRODE ENSEMBLES , 1995 .

[9]  R. W. Joyner,et al.  Simulated propagation of cardiac action potentials. , 1980, Biophysical journal.

[10]  C. Luo,et al.  A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. , 1994, Circulation research.

[11]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[12]  D. Noble,et al.  A model for human ventricular tissue. , 2004, American journal of physiology. Heart and circulatory physiology.

[13]  Ian F. Akyildiz,et al.  Nanonetworks: A new communication paradigm , 2008, Comput. Networks.

[14]  D. Noble,et al.  Rectifying Properties of Heart Muscle , 1960, Nature.

[15]  Richard D. Klafter,et al.  An In Vivo Study of Cardiac Pacemaker Optimization by Pulse Shape Modification , 1976, IEEE Transactions on Biomedical Engineering.

[16]  Yoshihisa Kurachi,et al.  Action potential and membrane currents of single pacemaker cells of the rabbit heart , 1984, Pflügers Archiv.

[17]  G. W. Beeler,et al.  Reconstruction of the action potential of ventricular myocardial fibres , 1977, The Journal of physiology.

[18]  Christoph Huber,et al.  The first batteryless, solar-powered cardiac pacemaker. , 2015, Heart rhythm.

[19]  D. Noble Cardiac Action and Pacemaker Potentials based on the Hodgkin-Huxley Equations , 1960, Nature.

[20]  D. Arrigan Nanoelectrodes, nanoelectrode arrays and their applications. , 2004, The Analyst.

[21]  Rahul Sarpeshkar,et al.  A Bio-Inspired Ultra-Energy-Efficient Analog-to-Digital Converter for Biomedical Applications , 2006, IEEE Transactions on Circuits and Systems I: Regular Papers.

[22]  C. Luo,et al.  A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction. , 1991, Circulation research.

[23]  Andrea Natale,et al.  Leadless Pacemakers: State of the Art and Future Perspectives. , 2018, Cardiac electrophysiology clinics.

[24]  R. Klafter,et al.  An optimally energized cardiac pacemaker. , 1973, IEEE transactions on bio-medical engineering.

[25]  Joshua Garland,et al.  Modelling the heart as a communication system , 2014, Journal of The Royal Society Interface.

[26]  Xavier Hesselbach,et al.  Nano-networks communication architecture: Modeling and functions , 2018, Nano Commun. Networks.

[27]  Ian F. Akyildiz,et al.  Nanonetworks: A new frontier in communications , 2012, 2010 International Conference on Security and Cryptography (SECRYPT).

[28]  Dinesh Bhatia,et al.  Pacemakers charging using body energy , 2010, Journal of pharmacy & bioallied sciences.

[29]  G M Whitesides,et al.  The once and future nanomachine. , 2001, Scientific American.

[30]  S. Pettersson,et al.  Artificial pacemaker for treatment of Adams-Stokes syndrome and slow heart rate☆ , 1963 .

[31]  B. Roth,et al.  Action potential propagation in a thick strand of cardiac muscle. , 1991, Circulation research.

[32]  Christoph Huber,et al.  Successful pacing using a batteryless sunlight-powered pacemaker. , 2014, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[33]  O. Akan,et al.  An Information Theoretical Analysis of Nanoscale Molecular Gap Junction Communication Channel Between Cardiomyocytes , 2013, IEEE Transactions on Nanotechnology.

[34]  Richard G Trohman,et al.  Cardiac resynchronization therapy: the state of the art , 2014, Expert review of cardiovascular therapy.

[35]  Ilangko Balasingham,et al.  Energy-efficiency of Cardiomyocyte Stimulation with Rectangular Pulses , 2019, Scientific Reports.

[36]  J A McWilliam,et al.  Electrical Stimulation of the Heart in Man , 1889, British medical journal.