Sigg / Xiao / Iaizzo Cardiac Electrophysiology Methods and Models

1. Auflage 2010
ISBN: 978-1-4419-6658-2
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 492 Seiten

Cardiovascular disease is the major cause of mortality and morbidity in the Western Hemisphere. While significant progress has been made in treating a major sub-category of cardiac disease, arrhythmias, significant unmet needs remain. In particular, every day, thousands of patients die because of arrhythmias in the US alone, and atrial fibrillation is the most common arrhythmia affecting millions of patients in the US alone at a given time. Therefore, there is a public need to continue to develop new and better therapies for arrhythmias. Accordingly, an ever increasing number of biomedical, pharmaceutical, and medical personnel is interested in studying various aspects of arrhythmias at a basic, translational, and applied level, both in industry (ie Biotech, Pharmaceutical and device), and in academia. Not only has our overall understanding of molecular bases of disease dramatically increased, but so has the number of available and emerging molecular, pharmacological or device treatment based therapies. This practical, state-of-the art handbook will summarize and review key research methods and protocols, their advantages and pitfalls, with a focus on practical implementation, and collaborative cross-functional research. The volume will include visual and easy-to-use graphics, bulleted summaries, boxed summary paragraphs, links to reference websites, equipment manufacturers where appropriate, photographs of typical experimental setups and so forth, to keep this book very focused on practical methods and implementation, and yet, provide enough theory that the principles are clearly understood and can be easily applied.

Daniel C. Sigg, MD, PhD is Adjunct Assistant Professor of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA Paul A. Iaizzo, PhD PhD is Professor of Surgery, Integrative Biology and Physiology and The Carlson School of Management, he is also Director of Education of the Lillehei Heart Institute and Associate Director for the Institute for Engineering in Medicine, he also holds the Medtronic Professorship for Visible Heart Research , University of Minnesota, Minneapolis, Minnesota, USA Yong-Fu Xiao, MD, PhD is Principal Scientist at Medtronic, Inc., New Therapies & Diagnostics Management, Cardiac Rhythm Disease Management, Mounds View, MN, USA Bin He, PhD is Distinguished McKnight University Professor and Professor of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA

Autoren/Hrsg.

Xiao, Yong-Fu

He, Bin

Sigg, Daniel C.

Iaizzo, Paul A.

Inhaltsverzeichnis

1;Cardiac Electrophysiology Methods and Models;3
1.1;Preface;5
1.2;Contents;7
1.3;Contributors;11
1.4;Chapter 1: Clinical Cardiac Electrophysiology: An Overview of Its Evolution;15
1.4.1;1.1 Electrocardiography;15
1.4.2;1.2 Device Therapy: Pacing, Defibrillation, and Monitoring;21
1.4.2.1;1.2.1 Early Development;22
1.4.2.2;1.2.2 Initial Evolution of Implantable Pulse Generators;23
1.4.2.3;1.2.3 Pacing Lead Development;25
1.4.2.4;1.2.4 Later Pacing System Advances;26
1.4.2.5;1.2.5 More Recent Pacing System Advances;28
1.4.2.6;1.2.6 Emergence of Implantable Defibrillators;29
1.4.2.7;1.2.7 Ambulatory Monitoring;31
1.4.3;1.3 Intracardiac Recording, Stimulation, and Autonomic Assessment;32
1.4.3.1;1.3.1 Early Studies Using Transcatheter Recordings;33
1.4.3.2;1.3.2 Premature Electrical Stimulation and Entrainment;33
1.4.3.3;1.3.3 Ablation;37
1.4.3.4;1.3.4 Autonomic Disturbances and Genetically Determined Susceptibility to Arrhythmias;38
1.4.3.5;1.3.5 Channelopathies: Genetically Determined Arrhythmias;39
1.4.4;1.4 Epicardial and Endocardial Mapping, Imaging, and Navigation;40
1.4.5;1.5 Antiarrhythmic Drug Therapy;43
1.4.6;1.6 Conclusion;45
1.4.7;References;46
1.5;Part I Overview;53
1.5.1;Chapter 2: Basic Cardiac Electrophysiology: Excitable Membranes;54
1.5.1.1;2.1 Introduction;54
1.5.1.2;2.2 Cell Membrane;55
1.5.1.3;2.3 Membrane Electrophysiology;57
1.5.1.3.1;2.3.1 Resting Membrane Potential;57
1.5.1.3.2;2.3.2 Equilibrium Potential and the Nernst Equation;58
1.5.1.3.3;2.3.3 Ion Channels and Membrane Currents;59
1.5.1.3.4;2.3.4 Action Potential;59
1.5.1.3.5;2.3.5 Refractoriness;60
1.5.1.3.6;2.3.6 Excitation–Contraction Coupling;62
1.5.1.4;2.4 Summary;64
1.5.1.5;References;64
1.5.2;Chapter 3: Cardiac Action Potentials, Ion Channels, and Gap Junctions;65
1.5.2.1;3.1 Introduction;65
1.5.2.2;3.2 Phases of the Action Potential;66
1.5.2.3;3.3 Ion Channels;67
1.5.2.3.1;3.3.1 Voltage-Gated Channels;68
1.5.2.3.1.1;3.3.1.1 Sodium Channel;68
1.5.2.3.1.2;3.3.1.2 Calcium Channel;71
1.5.2.3.1.3;3.3.1.3 Potassium Channels;72
1.5.2.3.1.3.1;The Inward Rectifier Current (IK1);73
1.5.2.3.1.3.2;The Transient Outward Current (ITo);74
1.5.2.3.1.3.3;The Delayed Rectifier Currents (IKr and IKs);74
1.5.2.3.1.3.4;The Ultra-Rapid Delayed Rectifier Current (IKur);75
1.5.2.3.2;3.3.2 Ligand-Gated Channels;75
1.5.2.3.3;3.3.3 Stretch-Activated Channels;76
1.5.2.3.4;3.3.4 Exchangers;76
1.5.2.3.5;3.3.5 Electrophysiological Heterogeneities in Ion Channel Expression;76
1.5.2.3.6;3.3.6 Changes in Ion Channel Expression by Cardiac Remodeling;77
1.5.2.4;3.4 Gap Junctions;78
1.5.2.4.1;3.4.1 Gap Junction Distribution in Cardiac Tissue;79
1.5.2.4.2;3.4.2 Redundancy of Connexins;79
1.5.2.4.3;3.4.3 Gap Junction Distribution in Cardiomyocytes;80
1.5.2.4.4;3.4.4 Homomeric and Heteromeric Expression;81
1.5.2.4.5;3.4.5 Remodeling of Connexin Expression;81
1.5.2.4.6;3.4.6 Transmural Differences in Connexins;82
1.5.2.5;3.5 Conclusion;83
1.5.2.6;References;83
1.5.3;Chapter 4: Anatomy and Physiology of the Cardiac Conduction System;85
1.5.3.1;4.1 Introduction;85
1.5.3.2;4.2 Overview of Cardiac Conduction;86
1.5.3.3;4.3 Cardiac Rate Control;90
1.5.3.4;4.4 Cardiac Action Potentials;92
1.5.3.5;4.5 Gap Junctions (Cell-to-Cell Conduction);93
1.5.3.6;4.6 The Atrioventricular Node and Bundle of His: Specific Features;96
1.5.3.7;4.7 Recording the Spread of Excitation Through the Heart;97
1.5.3.8;4.8 Future Research on the Heart’s Conduction System;99
1.5.3.9;4.9 Summary;99
1.5.3.10;References;99
1.5.4;Chapter 5: The Electrocardiogram and Clinical Cardiac Electrophysiology;102
1.5.4.1;5.1 Introduction;103
1.5.4.2;5.2 The Specialized Cardiac Conduction System;103
1.5.4.3;5.3 Electrocardiogram;104
1.5.4.3.1;5.3.1 ECG Leads;104
1.5.4.3.2;5.3.2 Waves and Intervals;105
1.5.4.3.2.1;5.3.2.1 P-wave;105
1.5.4.3.2.2;5.3.2.2 PR Interval;106
1.5.4.3.2.3;5.3.2.3 QRS Complex;106
1.5.4.3.2.4;5.3.2.4 ST Segment;107
1.5.4.3.2.5;5.3.2.5 T-wave;107
1.5.4.3.2.6;5.3.2.6 QT Interval;107
1.5.4.4;5.4 Mechanisms of Arrhythmias;107
1.5.4.5;5.5 Clinical Presentation and Diagnosis;108
1.5.4.6;5.6 Treatment Considerations;110
1.5.4.7;5.7 Bradyarrhythmias;111
1.5.4.7.1;5.7.1 Sinus Node Dysfunction;111
1.5.4.7.2;5.7.2 AV Block;112
1.5.4.8;5.8 Tachyarrhythmias;113
1.5.4.8.1;5.8.1 Premature Complexes;113
1.5.4.8.1.1;5.8.1.1 Atrial Premature Complexes;113
1.5.4.8.1.2;5.8.1.2 Multifocal Atrial Tachycardia;114
1.5.4.8.1.3;5.8.1.3 AV Junctional Premature Complexes;115
1.5.4.8.1.4;5.8.1.4 Ventricular Premature Complexes;115
1.5.4.8.2;5.8.2 Sinus Tachycardias;115
1.5.4.8.2.1;5.8.2.1 Physiological Sinus Tachycardia;115
1.5.4.8.2.2;5.8.2.2 Inappropriate Sinus Tachycardia;116
1.5.4.8.3;5.8.3 Paroxysmal Supraventricular Tachycardias;116
1.5.4.8.3.1;5.8.3.1 Sinus Node Reentry Tachycardia;116
1.5.4.8.3.2;5.8.3.2 Atrial Tachycardias;116
1.5.4.8.3.3;5.8.3.3 AV Nodal Reentry Tachycardia;117
1.5.4.8.3.4;5.8.3.4 AV Reciprocating Tachycardia Using Concealed Accessory Pathway;117
1.5.4.9;5.9 Wolff–Parkinson–White Syndrome;120
1.5.4.10;5.10 Nonparoxysmal Junctional Tachycardia;121
1.5.4.11;5.11 Atrial Flutter and Fibrillation;121
1.5.4.11.1;5.11.1 Atrial Flutter;121
1.5.4.11.2;5.11.2 Atrial Fibrillation;122
1.5.4.12;5.12 Ventricular Tachyarrhythmias;123
1.5.4.12.1;5.12.1 Ventricular Tachycardias;123
1.5.4.12.2;5.12.2 Ventricular Flutter and Ventricular Fibrillation;124
1.5.4.12.3;5.12.3 Accelerated Idioventricular Rhythm;125
1.5.4.12.4;5.12.4 Torsades de Pointes;125
1.5.4.13;5.13 Summary;125
1.5.4.14;Further Readings;126
1.6;Part II Methods and Models;128
1.6.1;Chapter 6: Principles of Electrophysiological In Vitro Measurements;129
1.6.1.1;6.1 Introduction;129
1.6.1.2;6.2 Electrodes;131
1.6.1.2.1;6.2.1 The Metal–Electrolyte Interface;132
1.6.1.2.2;6.2.2 Junction Potentials;132
1.6.1.2.3;6.2.3 Tip Potential;133
1.6.1.2.4;6.2.4 Glass Microelectrodes;134
1.6.1.3;6.3 Measurement of Membrane Potentials;135
1.6.1.3.1;6.3.1 Electrophysiological Measurement of Membrane Potentials;135
1.6.1.3.2;6.3.2 Fluorescence Techniques for Membrane Potential Measurement;136
1.6.1.4;6.4 Membrane Current Measurements;136
1.6.1.4.1;6.4.1 Classical Two-Electrode Voltage Clamp for the Measurement of Macroscopic Currents;136
1.6.1.4.2;6.4.2 The Patch Clamp Technique;137
1.6.1.4.3;6.4.3 High-Throughput Screening for the Pharmaceutical Industry;139
1.6.1.5;6.5 Solution and Pharmacology;140
1.6.1.6;6.6 Selective Measurements of Ion Activities;141
1.6.1.7;6.7 Troubleshooting;142
1.6.1.7.1;6.7.1 Low Series Resistances;142
1.6.1.7.2;6.7.2 Avoidance of Ground Loops;142
1.6.1.7.3;6.7.3 Stable Salt Bridges;143
1.6.1.7.4;6.7.4 Summary;143
1.6.1.8;References;144
1.6.2;Chapter 7: Cardiac Cellular Electrophysiological Modeling;145
1.6.2.1;7.1 Modeling Cardiac Cellular Electrophysiology;145
1.6.2.1.1;7.1.1 Simplified Models of Cardiac Cellular Electrophysiology;148
1.6.2.1.2;7.1.2 Biophysically Based Models of Cardiac Cellular Electrophysiology;152
1.6.2.2;7.2 Model Description;163
1.6.2.2.1;7.2.1 Worked Examples;163
1.6.2.2.1.1;7.2.1.1 One Model, Multiple Parameter Sets;164
1.6.2.2.1.2;7.2.1.2 Model Evolution;165
1.6.2.3;7.3 Conclusions;165
1.6.2.4;References;166
1.6.3;Chapter 8: Computer Modeling of Electrical Activation: From Cellular Dynamics to the Whole Heart;169
1.6.3.1;8.1 Introduction;169
1.6.3.2;8.2 Finite Elements and Material Coordinate Systems;170
1.6.3.3;8.3 Models of Cardiac Anatomy;173
1.6.3.4;8.4 Tissue Electrodynamics;176
1.6.3.4.1;8.4.1 The Bidomain Equations;176
1.6.3.4.2;8.4.2 The Monodomain Equations;178
1.6.3.5;8.5 Models of Cardiac Electrical Activation;179
1.6.3.5.1;8.5.1 Computational Issues;179
1.6.3.5.2;8.5.2 2D Tissue Models;180
1.6.3.5.3;8.5.3 3D Tissue Models;181
1.6.3.5.4;8.5.4 3D Ventricular Models;185
1.6.3.5.5;8.5.5 3D Atrial Models;187
1.6.3.6;8.6 Problems and Future Directions;189
1.6.3.7;References;192
1.6.4;Chapter 9: Detection and Measurement of Cardiac Ion Channels;196
1.6.4.1;9.1 Introduction;197
1.6.4.2;9.2 Apparatus;198
1.6.4.3;9.3 Methodology and Pitfalls;198
1.6.4.3.1;9.3.1 In Situ Hybridization with Digoxigenin-Labelled RNA Probes;198
1.6.4.3.1.1;9.3.1.1 Protocol Details;199
1.6.4.3.1.2;9.3.1.2 Generation of Digoxigenin-Labelled RNA Probes;202
1.6.4.3.1.3;9.3.1.3 Probe Design;202
1.6.4.3.1.4;9.3.1.4 Probe Length;203
1.6.4.3.1.5;9.3.1.5 Generation of Probe;203
1.6.4.3.1.6;9.3.1.6 Isolation of Insert (Probe) Sequences;203
1.6.4.3.1.7;9.3.1.7 Generation of Probe Template with RNA Polymerase Promoters;204
1.6.4.3.1.8;9.3.1.8 In Vitro Transcription;204
1.6.4.3.2;9.3.2 Quantitative PCR (qPCR);205
1.6.4.3.2.1;9.3.2.1 Protocol Details;205
1.6.4.3.2.2;9.3.2.2 Primer Design;211
1.6.4.3.3;9.3.3 Immunohistochemistry with Fluorescent Conjugated Secondary Antibodies;213
1.6.4.3.3.1;9.3.3.1 Protocol Details;214
1.6.4.4;9.4 New Emerging Techniques;219
1.6.4.4.1;9.4.1 Laser Capture Microdissection;219
1.6.4.4.2;9.4.2 qPCR Arrays;219
1.6.4.4.3;9.4.3 Protein Arrays;220
1.6.4.5;References;220
1.6.5;Chapter 10: Cell Culture Models and Methods;222
1.6.5.1;10.1 Introduction;222
1.6.5.2;10.2 Primary Cardiac Cell Culture;223
1.6.5.2.1;10.2.1 Adult Cardiomyocytes;223
1.6.5.2.2;10.2.2 Cultured Neonatal Cardiomyocytes;227
1.6.5.3;10.3 Cardiac Cell Lines;233
1.6.5.4;10.4 Stem Cell-Derived Myocytes;237
1.6.5.4.1;10.4.1 Embryonic Stem Cell-Derived Cardiomyocytes;237
1.6.5.4.2;10.4.2 Emerging Model: Induced-Pluripotent Stem Cells;241
1.6.5.5;10.5 Conclusion;241
1.6.5.6;References;241
1.6.6;Chapter 11: Isolated Tissue Models;245
1.6.6.1;11.1 Introduction;245
1.6.6.2;11.2 Description of Models;245
1.6.6.2.1;11.2.1 Isolated Trabeculae and Papillary Muscle Preparations;246
1.6.6.2.2;11.2.2 Isolated Ventricular Preparation;247
1.6.6.2.3;11.2.3 Isolated Atrioventricular Node Preparation;249
1.6.6.2.4;11.2.4 Isolated Atrial Preparation;251
1.6.6.3;11.3 Advantages, Limitations, and Pitfalls;252
1.6.6.3.1;11.3.1 Advantages and Limitations of Superfused Tissue Models;253
1.6.6.3.2;11.3.2 Advantages and Limitations of Perfused Tissue Models;254
1.6.6.4;11.4 Conclusion;255
1.6.6.5;References;255
1.6.7;Chapter 12: Isolated Heart Models;256
1.6.7.1;12.1 Introduction;256
1.6.7.2;12.2 Experimental Model and Methods;257
1.6.7.2.1;12.2.1 Species;257
1.6.7.2.2;12.2.2 Perfusion Method;258
1.6.7.2.3;12.2.3 Intracardiac Visualization;259
1.6.7.2.4;12.2.4 Electrophysiological Studies;259
1.6.7.2.5;12.2.5 Device–Tissue Interaction;261
1.6.7.3;12.3 Limitations;262
1.6.7.4;12.4 Conclusion;264
1.6.7.5;References;265
1.6.8;Chapter 13: Small Animal Models for Arrhythmia Studies;268
1.6.8.1;13.1 Introduction;269
1.6.8.2;13.2 Nongenetic Small Animal Models for Arrhythmia Studies;269
1.6.8.2.1;13.2.1 Myocardial Infarction Model;269
1.6.8.2.2;13.2.2 Hypertrophy and Heart Failure Model;271
1.6.8.2.3;13.2.3 Chronic Complete Atrioventricular Block Model;272
1.6.8.2.4;13.2.4 Cardiac Dyssynchrony Model;274
1.6.8.2.5;13.2.5 Atrial Fibrillation Model;274
1.6.8.3;13.3 Genetically Engineered Small Animal Models for Arrhythmia Studies;275
1.6.8.3.1;13.3.1 Long QT Syndromes;276
1.6.8.3.2;13.3.2 Brugada Syndrome;277
1.6.8.3.3;13.3.3 Catecholaminergic Polymorphic Ventricular Tachycardia;278
1.6.8.3.4;13.3.4 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C);280
1.6.8.3.5;13.3.5 Familial Atrial Fibrillation;280
1.6.8.4;13.4 Summary;280
1.6.8.5;References;282
1.6.9;Chapter 14: Use of Large Animal Models for Cardiac Electrophysiology Studies;287
1.6.9.1;14.1 Introduction;287
1.6.9.2;14.2 Choosing the Right Animal Model;288
1.6.9.2.1;14.2.1 Rate of Growth;289
1.6.9.2.2;14.2.2 Arrhythmogenicity;289
1.6.9.2.3;14.2.3 Comparative Anatomy;289
1.6.9.3;14.3 Lead Placement;290
1.6.9.4;14.4 His Bundle Pacing;293
1.6.9.5;14.5 Ablation Studies;294
1.6.9.6;14.6 Anesthetics and Monitoring;294
1.6.9.6.1;14.6.1 Invasive Monitoring;296
1.6.9.6.2;14.6.2 Accessing the Heart;297
1.6.9.7;14.7 Common Cardiac Electrophysiology Interventions;299
1.6.9.8;14.8 Animal Models of Disease States;301
1.6.9.8.1;14.8.1 Congestive Heart Failure Models;302
1.6.9.8.2;14.8.2 Acute and Chronic Atrial Fibrillation Models;304
1.6.9.8.3;14.8.3 Animal Models of Ventricular Fibrillation;305
1.6.9.8.4;14.8.4 Animal Models of Myocardial Infarction, Ischemia;305
1.6.9.9;14.9 Summary;308
1.6.9.10;References;308
1.6.10;Chapter 15: Optical Mapping and Calcium Imaging;311
1.6.10.1;15.1 Introduction;311
1.6.10.2;15.2 Brief Description of Optical Mapping Principles;311
1.6.10.3;15.3 Principles of Wavelength Ratiometry in Optical Mapping;312
1.6.10.4;15.4 Detailed Principles of Ratiometric Calcium Imaging;316
1.6.10.5;15.5 Application and Practical Implementation;317
1.6.10.5.1;15.5.1 Light Source;322
1.6.10.5.2;15.5.2 Light Guide;322
1.6.10.5.3;15.5.3 Tissue Interface and Interaction;323
1.6.10.5.4;15.5.4 Fluorescent Dye;324
1.6.10.5.5;15.5.5 Tissue Interaction;325
1.6.10.5.6;15.5.6 Optics;325
1.6.10.5.7;15.5.7 Detectors;327
1.6.10.6;15.6 Pitfalls, Limitations, and Artifacts;328
1.6.10.6.1;15.6.1 Artifacts of Dye and Excitation Light;328
1.6.10.6.2;15.6.2 Artifacts of Motion;328
1.6.10.6.3;15.6.3 Artifacts of Tissue Filtering and Interaction;329
1.6.10.6.4;15.6.4 Artifacts of Optical Signal Magnitude;330
1.6.10.7;15.7 New and Emerging Techniques/Models/Technologies;330
1.6.10.8;15.8 Conclusion;331
1.6.10.9;15.9 Additional References and Resources;331
1.6.10.10;References;332
1.6.11;Chapter 16: Electrophysiology of Single Cardiomyocytes: Patch Clamp and Other Recording Methods;334
1.6.11.1;16.1 Introduction;334
1.6.11.1.1;16.1.1 Importance of Ion Channel Function in the Heart;335
1.6.11.1.2;16.1.2 Understanding Ion Channel Behavior Through Electrical Analogues;335
1.6.11.1.3;16.1.3 Terminology;337
1.6.11.2;16.2 Apparatus for Single-Cell Recordings;338
1.6.11.2.1;16.2.1 Microelectrodes;338
1.6.11.2.2;16.2.2 Headstage, Amplifier, and Data Acquisition System;339
1.6.11.2.3;16.2.3 Cell and Tissue Baths;341
1.6.11.2.4;16.2.4 Microscope, Micromanipulator, and Vibration Isolation Table;341
1.6.11.3;16.3 Recording Modes;342
1.6.11.3.1;16.3.1 Extracellular Recording;342
1.6.11.3.2;16.3.2 Intracellular Recording;343
1.6.11.3.3;16.3.3 Current Cl344
1.6.11.3.4;16.3.4 Voltage Cl346
1.6.11.4;16.4 Examples of Experimental Protocols;347
1.6.11.4.1;16.4.1 Protocol for Intracellular Recording of Human Cardiac Action Potentials;347
1.6.11.4.2;16.4.2 Protocol for Patch Clamp Recording of Ih in hHCN4-Transfected HEK293 Cells;348
1.6.11.5;16.5 Pitfalls and Troubleshooting;350
1.6.11.5.1;16.5.1 Tissue and Cell Viability;351
1.6.11.5.2;16.5.2 Microelectrodes;351
1.6.11.5.3;16.5.3 Electrical Noise;351
1.6.11.6;16.6 Emerging Technologies for Cellular Electrophysiology;352
1.6.11.7;References;352
1.6.12;Chapter 17: Invasive Electroanatomical Mapping and Navigation;354
1.6.12.1;17.1 Introduction;354
1.6.12.2;17.2 The Use of Electroanatomical Mapping for the Treatment of Atrial Arrhythmias;355
1.6.12.2.1;17.2.1 Atrial Tachycardia;355
1.6.12.2.2;17.2.2 Atrial Flutter;355
1.6.12.2.3;17.2.3 Atrial Fibrillation;355
1.6.12.3;17.3 The Use of Electroanatomical Mapping for the Treatment of Ventricular Tachycardias;357
1.6.12.3.1;17.3.1 Automatic Ventricular Tachycardia;357
1.6.12.3.2;17.3.2 Reentrant Ventricular Tachycardia;358
1.6.12.4;17.4 The Use of Electroanatomical Mapping for the Treatment of Arrhythmias in Patients with Congenital Heart Disease;359
1.6.12.5;17.5 Types of Electroanatomical Mapping Systems;360
1.6.12.5.1;17.5.1 Magnetic-Based Mapping;360
1.6.12.5.2;17.5.2 Impedance-Based Mapping;360
1.6.12.6;17.6 Pitfalls and Troubleshooting;360
1.6.12.7;References;361
1.6.13;Chapter 18: Cardiac Electrophysiological Imaging: Solving the Inverse Problem of Electrocardiography;362
1.6.13.1;18.1 Introduction;362
1.6.13.2;18.2 Moving Dipole Source Imaging;364
1.6.13.3;18.3 Heart Surface Distributed Source Imaging;365
1.6.13.3.1;18.3.1 Epicardial Potential Imaging;365
1.6.13.3.2;18.3.2 Heart Surface Activation Imaging;366
1.6.13.4;18.4 Three-dimensional Source Imaging;368
1.6.13.4.1;18.4.1 Inverse Estimation of 3D Dipole Distribution;369
1.6.13.4.2;18.4.2 Heart Model-Based 3D Activation Imaging;370
1.6.13.4.3;18.4.3 Physical Model-Based 3D Activation Imaging;372
1.6.13.5;18.5 Imaging Cardiac Sources from Intracavitary Recordings;374
1.6.13.6;18.6 Discussion;375
1.6.13.7;References;376
1.6.14;Chapter 19: Traditional Electrophysiological Mapping;379
1.6.14.1;19.1 Introduction;379
1.6.14.2;19.2 Description of Apparatus;380
1.6.14.2.1;19.2.1 Electrode Catheters;380
1.6.14.2.2;19.2.2 Recording Apparatus;380
1.6.14.2.3;19.2.3 Stimulation Apparatus;381
1.6.14.3;19.3 Basic Mechanisms of Common Tachycardia;381
1.6.14.3.1;19.3.1 Reentry;381
1.6.14.3.2;19.3.2 Automaticity;382
1.6.14.3.3;19.3.3 Triggered Activity;383
1.6.14.4;19.4 Activation Sequence Mapping;383
1.6.14.4.1;19.4.1 Local Electrogram Morphology;384
1.6.14.4.2;19.4.2 Sinus Rhythm Mapping;387
1.6.14.5;19.5 Pace Mapping;387
1.6.14.6;19.6 Entrainment;388
1.6.14.6.1;19.6.1 End-Entrainment Data;389
1.6.14.7;19.7 Additional Mapping Maneuvers;393
1.6.14.7.1;19.7.1 Node-Refractory Ventricular Pacing During NCT;393
1.6.14.7.2;19.7.2 Parahissian Pacing;393
1.6.14.8;19.8 Pitfalls and Troubleshooting;396
1.6.14.9;19.9 Summary;396
1.6.14.10;References;397
1.6.15;Chapter 20: Multi-channel System for Analysis of Cardiac Rhythmicity and Conductivity In Vitro;398
1.6.15.1;20.1 Introduction;398
1.6.15.2;20.2 Multi-channel System;400
1.6.15.2.1;20.2.1 Hardware;400
1.6.15.2.2;20.2.2 Data Acquisition and Analysis;400
1.6.15.2.3;20.2.3 Vibration Isolation and Noise Reduction;401
1.6.15.3;20.3 Rhythmicity of Cultured Cardiomyocytes;402
1.6.15.3.1;20.3.1 HL-5 Cells;403
1.6.15.3.2;20.3.2 Neonatal Rat Cardiomyocytes;404
1.6.15.3.3;20.3.3 Cardiomyocytes Derived from Stem Cells;406
1.6.15.3.4;20.3.4 Myocardial Tissue Slices;406
1.6.15.3.5;20.3.5 Biopacing Assessment;407
1.6.15.3.6;20.3.6 Pharmacological Effects;409
1.6.15.4;20.4 Cardiac Electrical Conductivity In Vitro;411
1.6.15.4.1;20.4.1 Conductivity Measurement;411
1.6.15.4.2;20.4.2 Creation of Conduction Block;411
1.6.15.4.3;20.4.3 Cardiac Fibrous Cells for Conduction Repair;413
1.6.15.4.4;20.4.4 Conduction Repair by Stem Cells;416
1.6.15.5;20.5 Summary;417
1.6.15.6;References;418
1.6.16;Chapter 21: Cardiac CT/MRI Imaging for Electrophysiology;421
1.6.16.1;21.1 Introduction;421
1.6.16.2;21.2 Intracardiac Echocardiography;422
1.6.16.3;21.3 Computed Tomography;424
1.6.16.3.1;21.3.1 Ablation of Atrial Fibrillation;424
1.6.16.3.2;21.3.2 Atrial Flutter Ablation;427
1.6.16.3.3;21.3.3 Biventricular Lead Insertion for Cardiac Resynchronization Therapy;428
1.6.16.3.4;21.3.4 Evaluation of Arrhythmogenic Substrate;429
1.6.16.4;21.4 Magnetic Resonance Imaging;430
1.6.16.4.1;21.4.1 Atrial Fibrillation Ablation;430
1.6.16.4.2;21.4.2 Ventricular Tachycardia Ablation;431
1.6.16.4.3;21.4.3 Subsequent Imaging of Ablation Lesions with Magnetic Resonance Imaging;431
1.6.16.4.4;21.4.4 Real-Time Magnetic Resonance Imaging;432
1.6.16.5;21.5 Fusion Imaging/Multimodal Imaging;433
1.6.16.6;21.6 Conclusion;434
1.6.16.7;References;434
1.7;Part III Putting It All Together;440
1.7.1;Chapter 22: Introduction to Translational Research;441
1.7.1.1;22.1 Introduction;441
1.7.1.2;22.2 Determining the Clinical Problem;443
1.7.1.2.1;22.2.1 Cardiac Arrest;443
1.7.1.2.2;22.2.2 Heart Failure;443
1.7.1.2.3;22.2.3 Atrial Fibrillation;444
1.7.1.3;22.3 Investigate Mechanisms of Disease;444
1.7.1.3.1;22.3.1 Arrhythmias;444
1.7.1.3.2;22.3.2 Heart Failure;446
1.7.1.4;22.4 Define Target and Develop Therapy;446
1.7.1.4.1;22.4.1 Cardiac Arrest;447
1.7.1.4.2;22.4.2 Heart Failure;447
1.7.1.4.3;22.4.3 Atrial Fibrillation;448
1.7.1.5;22.5 Test Therapy;448
1.7.1.5.1;22.5.1 Cardiac Arrest;449
1.7.1.5.2;22.5.2 Heart Failure;449
1.7.1.5.2.1;22.5.2.1 Chronic Myocardial Ischemia;450
1.7.1.5.2.2;22.5.2.2 Dilated Cardiomyopathy;450
1.7.1.5.2.3;22.5.2.3 Other Models of Heart Failure;451
1.7.1.5.3;22.5.3 Atrial Fibrillation;451
1.7.1.6;22.6 Clinical Trials;452
1.7.1.6.1;22.6.1 Types of Clinical Trials;452
1.7.1.6.2;22.6.2 Phases of Clinical Trials;452
1.7.1.7;22.7 Conclusion;453
1.7.1.8;References;454
1.7.2;Chapter 23: Clinical Perspective: Electrophysiology in the Young and Patients with Congenital Heart Disease;456
1.7.2.1;23.1 Introduction;457
1.7.2.2;23.2 “Natural History” Issues of Arrhythmias in Young Patients;457
1.7.2.2.1;23.2.1 Fetal and Newborn Arrhythmias;457
1.7.2.2.2;23.2.2 Arrhythmia Under One Year;459
1.7.2.2.3;23.2.3 Recurrent and Onset of SVT;459
1.7.2.2.4;23.2.4 Late Childhood and Early Adulthood: the Effects of Postoperative Anatomy and Physiology;460
1.7.2.2.5;23.2.5 Arrhythmia and CHD in Middle Aged and Older Patients;464
1.7.2.2.6;23.2.6 Summary of “Natural History” Aspects;466
1.7.2.3;23.3 Antiarrhythmic Drug Therapies in Young Patients;466
1.7.2.3.1;23.3.1 Pharmacokinetics of AADs in Pediatrics;467
1.7.2.3.2;23.3.2 Important Clinical Considerations for AAD Administration in Pediatric and CHD Patients;467
1.7.2.4;23.4 Clinical Use and Indications for Interventions in the Young;468
1.7.2.4.1;23.4.1 Catheter Ablation;468
1.7.2.4.2;23.4.2 Pacemaker Implantation;469
1.7.2.4.3;23.4.3 Implantable Cardiac Defibrillators;470
1.7.2.4.4;23.4.4 Cardiac Resynchronization Therapies;471
1.7.2.5;23.5 Looking Ahead: Cardiac Rhythm, Device Therapies, and Sudden Cardiac Death in the Adult Population with CHD;472
1.7.2.6;23.6 Putting It All Together;473
1.7.2.7;References;474
1.8;Index;477