Effects of mechano-electric feedback on scroll wave stability in human ventricular fibrillation. 2013

Yuxuan Hu, and Viatcheslav Gurev, and Jason Constantino, and Jason D Bayer, and Natalia A Trayanova
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.

Recruitment of stretch-activated channels, one of the mechanisms of mechano-electric feedback, has been shown to influence the stability of scroll waves, the waves that underlie reentrant arrhythmias. However, a comprehensive study to examine the effects of recruitment of stretch-activated channels with different reversal potentials and conductances on scroll wave stability has not been undertaken; the mechanisms by which stretch-activated channel opening alters scroll wave stability are also not well understood. The goals of this study were to test the hypothesis that recruitment of stretch-activated channels affects scroll wave stability differently depending on stretch-activated channel reversal potential and channel conductance, and to uncover the relevant mechanisms underlying the observed behaviors. We developed a strongly-coupled model of human ventricular electromechanics that incorporated human ventricular geometry and fiber and sheet orientation reconstructed from MR and diffusion tensor MR images. Since a wide variety of reversal potentials and channel conductances have been reported for stretch-activated channels, two reversal potentials, -60 mV and -10 mV, and a range of channel conductances (0 to 0.07 mS/µF) were implemented. Opening of stretch-activated channels with a reversal potential of -60 mV diminished scroll wave breakup for all values of conductances by flattening heterogeneously the action potential duration restitution curve. Opening of stretch-activated channels with a reversal potential of -10 mV inhibited partially scroll wave breakup at low conductance values (from 0.02 to 0.04 mS/µF) by flattening heterogeneously the conduction velocity restitution relation. For large conductance values (>0.05 mS/µF), recruitment of stretch-activated channels with a reversal potential of -10 mV did not reduce the likelihood of scroll wave breakup because Na channel inactivation in regions of large stretch led to conduction block, which counteracted the increased scroll wave stability due to an overall flatter conduction velocity restitution.

UI MeSH Term Description Entries
D008465 Mechanoreceptors Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptor cells include the INNER EAR hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with non-neural accessory structures. Golgi Tendon Organ,Golgi Tendon Organs,Krause's End Bulb,Krause's End Bulbs,Mechanoreceptor,Mechanoreceptor Cell,Meissner's Corpuscle,Neurotendinous Spindle,Neurotendinous Spindles,Receptors, Stretch,Ruffini's Corpuscle,Ruffini's Corpuscles,Stretch Receptor,Stretch Receptors,Mechanoreceptor Cells,Bulb, Krause's End,Bulbs, Krause's End,Cell, Mechanoreceptor,Cells, Mechanoreceptor,Corpuscle, Meissner's,Corpuscle, Ruffini's,Corpuscles, Ruffini's,End Bulb, Krause's,End Bulbs, Krause's,Krause End Bulb,Krause End Bulbs,Krauses End Bulb,Krauses End Bulbs,Meissner Corpuscle,Meissners Corpuscle,Organ, Golgi Tendon,Organs, Golgi Tendon,Receptor, Stretch,Ruffini Corpuscle,Ruffini Corpuscles,Ruffinis Corpuscle,Ruffinis Corpuscles,Spindle, Neurotendinous,Spindles, Neurotendinous,Tendon Organ, Golgi,Tendon Organs, Golgi
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D006329 Heart Conduction System An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart. Conduction System, Heart,Conduction Systems, Heart,Heart Conduction Systems,System, Heart Conduction,Systems, Heart Conduction
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014693 Ventricular Fibrillation A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST. Fibrillation, Ventricular,Fibrillations, Ventricular,Ventricular Fibrillations
D015640 Ion Channel Gating The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability. Gating, Ion Channel,Gatings, Ion Channel,Ion Channel Gatings
D025461 Feedback, Physiological A mechanism of communication with a physiological system for homeostasis, adaptation, etc. Physiological feedback is mediated through extensive feedback mechanisms that use physiological cues as feedback loop signals to control other systems. Feedback, Biochemical,Feedback Inhibition, Biochemical,Feedback Regulation, Biochemical,Feedback Stimulation, Biochemical,Negative Feedback, Biochemical,Positive Feedback, Biochemical,Biochemical Feedback,Biochemical Feedback Inhibition,Biochemical Feedback Inhibitions,Biochemical Feedback Regulation,Biochemical Feedback Regulations,Biochemical Feedback Stimulation,Biochemical Feedback Stimulations,Biochemical Feedbacks,Biochemical Negative Feedback,Biochemical Negative Feedbacks,Biochemical Positive Feedback,Biochemical Positive Feedbacks,Feedback Inhibitions, Biochemical,Feedback Regulations, Biochemical,Feedback Stimulations, Biochemical,Feedback, Biochemical Negative,Feedback, Biochemical Positive,Feedbacks, Biochemical,Feedbacks, Biochemical Negative,Feedbacks, Biochemical Positive,Feedbacks, Physiological,Inhibition, Biochemical Feedback,Inhibitions, Biochemical Feedback,Negative Feedbacks, Biochemical,Physiological Feedback,Physiological Feedbacks,Positive Feedbacks, Biochemical,Regulation, Biochemical Feedback,Regulations, Biochemical Feedback,Stimulation, Biochemical Feedback,Stimulations, Biochemical Feedback

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