Cardiac Electrophysiology Methods and Models (eBook)
XIV, 492 Seiten
Springer US (Verlag)
978-1-4419-6658-2 (ISBN)
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
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
Cardiac Electrophysiology Methods and Models 3
Preface 5
Contents 7
Contributors 11
Chapter 1: Clinical Cardiac Electrophysiology: An Overview of Its Evolution 15
1.1 Electrocardiography 15
1.2 Device Therapy: Pacing, Defibrillation, and Monitoring 21
1.2.1 Early Development 22
1.2.2 Initial Evolution of Implantable Pulse Generators 23
1.2.3 Pacing Lead Development 25
1.2.4 Later Pacing System Advances 26
1.2.5 More Recent Pacing System Advances 28
1.2.6 Emergence of Implantable Defibrillators 29
1.2.7 Ambulatory Monitoring 31
1.3 Intracardiac Recording, Stimulation, and Autonomic Assessment 32
1.3.1 Early Studies Using Transcatheter Recordings 33
1.3.2 Premature Electrical Stimulation and Entrainment 33
1.3.3 Ablation 37
1.3.4 Autonomic Disturbances and Genetically Determined Susceptibility to Arrhythmias 38
1.3.5 Channelopathies: Genetically Determined Arrhythmias 39
1.4 Epicardial and Endocardial Mapping, Imaging, and Navigation 40
1.5 Antiarrhythmic Drug Therapy 43
1.6 Conclusion 45
References 46
Part I Overview 53
Chapter 2: Basic Cardiac Electrophysiology: Excitable Membranes 54
2.1 Introduction 54
2.2 Cell Membrane 55
2.3 Membrane Electrophysiology 57
2.3.1 Resting Membrane Potential 57
2.3.2 Equilibrium Potential and the Nernst Equation 58
2.3.3 Ion Channels and Membrane Currents 59
2.3.4 Action Potential 59
2.3.5 Refractoriness 60
2.3.6 Excitation–Contraction Coupling 62
2.4 Summary 64
References 64
Chapter 3: Cardiac Action Potentials, Ion Channels, and Gap Junctions 65
3.1 Introduction 65
3.2 Phases of the Action Potential 66
3.3 Ion Channels 67
3.3.1 Voltage-Gated Channels 68
3.3.1.1 Sodium Channel 68
3.3.1.2 Calcium Channel 71
3.3.1.3 Potassium Channels 72
The Inward Rectifier Current (IK1) 73
The Transient Outward Current (ITo) 74
The Delayed Rectifier Currents (IKr and IKs) 74
The Ultra-Rapid Delayed Rectifier Current (IKur) 75
3.3.2 Ligand-Gated Channels 75
3.3.3 Stretch-Activated Channels 76
3.3.4 Exchangers 76
3.3.5 Electrophysiological Heterogeneities in Ion Channel Expression 76
3.3.6 Changes in Ion Channel Expression by Cardiac Remodeling 77
3.4 Gap Junctions 78
3.4.1 Gap Junction Distribution in Cardiac Tissue 79
3.4.2 Redundancy of Connexins 79
3.4.3 Gap Junction Distribution in Cardiomyocytes 80
3.4.4 Homomeric and Heteromeric Expression 81
3.4.5 Remodeling of Connexin Expression 81
3.4.6 Transmural Differences in Connexins 82
3.5 Conclusion 83
References 83
Chapter 4: Anatomy and Physiology of the Cardiac Conduction System 85
4.1 Introduction 85
4.2 Overview of Cardiac Conduction 86
4.3 Cardiac Rate Control 90
4.4 Cardiac Action Potentials 92
4.5 Gap Junctions (Cell-to-Cell Conduction) 93
4.6 The Atrioventricular Node and Bundle of His: Specific Features 96
4.7 Recording the Spread of Excitation Through the Heart 97
4.8 Future Research on the Heart’s Conduction System 99
4.9 Summary 99
References 99
Chapter 5: The Electrocardiogram and Clinical Cardiac Electrophysiology 102
5.1 Introduction 103
5.2 The Specialized Cardiac Conduction System 103
5.3 Electrocardiogram 104
5.3.1 ECG Leads 104
5.3.2 Waves and Intervals 105
5.3.2.1 P-wave 105
5.3.2.2 PR Interval 106
5.3.2.3 QRS Complex 106
5.3.2.4 ST Segment 107
5.3.2.5 T-wave 107
5.3.2.6 QT Interval 107
5.4 Mechanisms of Arrhythmias 107
5.5 Clinical Presentation and Diagnosis 108
5.6 Treatment Considerations 110
5.7 Bradyarrhythmias 111
5.7.1 Sinus Node Dysfunction 111
5.7.2 AV Block 112
5.8 Tachyarrhythmias 113
5.8.1 Premature Complexes 113
5.8.1.1 Atrial Premature Complexes 113
5.8.1.2 Multifocal Atrial Tachycardia 114
5.8.1.3 AV Junctional Premature Complexes 115
5.8.1.4 Ventricular Premature Complexes 115
5.8.2 Sinus Tachycardias 115
5.8.2.1 Physiological Sinus Tachycardia 115
5.8.2.2 Inappropriate Sinus Tachycardia 116
5.8.3 Paroxysmal Supraventricular Tachycardias 116
5.8.3.1 Sinus Node Reentry Tachycardia 116
5.8.3.2 Atrial Tachycardias 116
5.8.3.3 AV Nodal Reentry Tachycardia 117
5.8.3.4 AV Reciprocating Tachycardia Using Concealed Accessory Pathway 117
5.9 Wolff–Parkinson–White Syndrome 120
5.10 Nonparoxysmal Junctional Tachycardia 121
5.11 Atrial Flutter and Fibrillation 121
5.11.1 Atrial Flutter 121
5.11.2 Atrial Fibrillation 122
5.12 Ventricular Tachyarrhythmias 123
5.12.1 Ventricular Tachycardias 123
5.12.2 Ventricular Flutter and Ventricular Fibrillation 124
5.12.3 Accelerated Idioventricular Rhythm 125
5.12.4 Torsades de Pointes 125
5.13 Summary 125
Further Readings 126
Part II Methods and Models 128
Chapter 6: Principles of Electrophysiological In Vitro Measurements 129
6.1 Introduction 129
6.2 Electrodes 131
6.2.1 The Metal–Electrolyte Interface 132
6.2.2 Junction Potentials 132
6.2.3 Tip Potential 133
6.2.4 Glass Microelectrodes 134
6.3 Measurement of Membrane Potentials 135
6.3.1 Electrophysiological Measurement of Membrane Potentials 135
6.3.2 Fluorescence Techniques for Membrane Potential Measurement 136
6.4 Membrane Current Measurements 136
6.4.1 Classical Two-Electrode Voltage Clamp for the Measurement of Macroscopic Currents 136
6.4.2 The Patch Clamp Technique 137
6.4.3 High-Throughput Screening for the Pharmaceutical Industry 139
6.5 Solution and Pharmacology 140
6.6 Selective Measurements of Ion Activities 141
6.7 Troubleshooting 142
6.7.1 Low Series Resistances 142
6.7.2 Avoidance of Ground Loops 142
6.7.3 Stable Salt Bridges 143
6.7.4 Summary 143
References 144
Chapter 7: Cardiac Cellular Electrophysiological Modeling 145
7.1 Modeling Cardiac Cellular Electrophysiology 145
7.1.1 Simplified Models of Cardiac Cellular Electrophysiology 148
7.1.2 Biophysically Based Models of Cardiac Cellular Electrophysiology 152
7.2 Model Description 163
7.2.1 Worked Examples 163
7.2.1.1 One Model, Multiple Parameter Sets 164
7.2.1.2 Model Evolution 165
7.3 Conclusions 165
References 166
Chapter 8: Computer Modeling of Electrical Activation: From Cellular Dynamics to the Whole Heart 169
8.1 Introduction 169
8.2 Finite Elements and Material Coordinate Systems 170
8.3 Models of Cardiac Anatomy 173
8.4 Tissue Electrodynamics 176
8.4.1 The Bidomain Equations 176
8.4.2 The Monodomain Equations 178
8.5 Models of Cardiac Electrical Activation 179
8.5.1 Computational Issues 179
8.5.2 2D Tissue Models 180
8.5.3 3D Tissue Models 181
8.5.4 3D Ventricular Models 185
8.5.5 3D Atrial Models 187
8.6 Problems and Future Directions 189
References 192
Chapter 9: Detection and Measurement of Cardiac Ion Channels 196
9.1 Introduction 197
9.2 Apparatus 198
9.3 Methodology and Pitfalls 198
9.3.1 In Situ Hybridization with Digoxigenin-Labelled RNA Probes 198
9.3.1.1 Protocol Details 199
9.3.1.2 Generation of Digoxigenin-Labelled RNA Probes 202
9.3.1.3 Probe Design 202
9.3.1.4 Probe Length 203
9.3.1.5 Generation of Probe 203
9.3.1.6 Isolation of Insert (Probe) Sequences 203
9.3.1.7 Generation of Probe Template with RNA Polymerase Promoters 204
9.3.1.8 In Vitro Transcription 204
9.3.2 Quantitative PCR (qPCR) 205
9.3.2.1 Protocol Details 205
9.3.2.2 Primer Design 211
9.3.3 Immunohistochemistry with Fluorescent Conjugated Secondary Antibodies 213
9.3.3.1 Protocol Details 214
9.4 New Emerging Techniques 219
9.4.1 Laser Capture Microdissection 219
9.4.2 qPCR Arrays 219
9.4.3 Protein Arrays 220
References 220
Chapter 10: Cell Culture Models and Methods 222
10.1 Introduction 222
10.2 Primary Cardiac Cell Culture 223
10.2.1 Adult Cardiomyocytes 223
10.2.2 Cultured Neonatal Cardiomyocytes 227
10.3 Cardiac Cell Lines 233
10.4 Stem Cell-Derived Myocytes 237
10.4.1 Embryonic Stem Cell-Derived Cardiomyocytes 237
10.4.2 Emerging Model: Induced-Pluripotent Stem Cells 241
10.5 Conclusion 241
References 241
Chapter 11: Isolated Tissue Models 245
11.1 Introduction 245
11.2 Description of Models 245
11.2.1 Isolated Trabeculae and Papillary Muscle Preparations 246
11.2.2 Isolated Ventricular Preparation 247
11.2.3 Isolated Atrioventricular Node Preparation 249
11.2.4 Isolated Atrial Preparation 251
11.3 Advantages, Limitations, and Pitfalls 252
11.3.1 Advantages and Limitations of Superfused Tissue Models 253
11.3.2 Advantages and Limitations of Perfused Tissue Models 254
11.4 Conclusion 255
References 255
Chapter 12: Isolated Heart Models 256
12.1 Introduction 256
12.2 Experimental Model and Methods 257
12.2.1 Species 257
12.2.2 Perfusion Method 258
12.2.3 Intracardiac Visualization 259
12.2.4 Electrophysiological Studies 259
12.2.5 Device–Tissue Interaction 261
12.3 Limitations 262
12.4 Conclusion 264
References 265
Chapter 13: Small Animal Models for Arrhythmia Studies 268
13.1 Introduction 269
13.2 Nongenetic Small Animal Models for Arrhythmia Studies 269
13.2.1 Myocardial Infarction Model 269
13.2.2 Hypertrophy and Heart Failure Model 271
13.2.3 Chronic Complete Atrioventricular Block Model 272
13.2.4 Cardiac Dyssynchrony Model 274
13.2.5 Atrial Fibrillation Model 274
13.3 Genetically Engineered Small Animal Models for Arrhythmia Studies 275
13.3.1 Long QT Syndromes 276
13.3.2 Brugada Syndrome 277
13.3.3 Catecholaminergic Polymorphic Ventricular Tachycardia 278
13.3.4 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) 280
13.3.5 Familial Atrial Fibrillation 280
13.4 Summary 280
References 282
Chapter 14: Use of Large Animal Models for Cardiac Electrophysiology Studies 287
14.1 Introduction 287
14.2 Choosing the Right Animal Model 288
14.2.1 Rate of Growth 289
14.2.2 Arrhythmogenicity 289
14.2.3 Comparative Anatomy 289
14.3 Lead Placement 290
14.4 His Bundle Pacing 293
14.5 Ablation Studies 294
14.6 Anesthetics and Monitoring 294
14.6.1 Invasive Monitoring 296
14.6.2 Accessing the Heart 297
14.7 Common Cardiac Electrophysiology Interventions 299
14.8 Animal Models of Disease States 301
14.8.1 Congestive Heart Failure Models 302
14.8.2 Acute and Chronic Atrial Fibrillation Models 304
14.8.3 Animal Models of Ventricular Fibrillation 305
14.8.4 Animal Models of Myocardial Infarction, Ischemia 305
14.9 Summary 308
References 308
Chapter 15: Optical Mapping and Calcium Imaging 311
15.1 Introduction 311
15.2 Brief Description of Optical Mapping Principles 311
15.3 Principles of Wavelength Ratiometry in Optical Mapping 312
15.4 Detailed Principles of Ratiometric Calcium Imaging 316
15.5 Application and Practical Implementation 317
15.5.1 Light Source 322
15.5.2 Light Guide 322
15.5.3 Tissue Interface and Interaction 323
15.5.4 Fluorescent Dye 324
15.5.5 Tissue Interaction 325
15.5.6 Optics 325
15.5.7 Detectors 327
15.6 Pitfalls, Limitations, and Artifacts 328
15.6.1 Artifacts of Dye and Excitation Light 328
15.6.2 Artifacts of Motion 328
15.6.3 Artifacts of Tissue Filtering and Interaction 329
15.6.4 Artifacts of Optical Signal Magnitude 330
15.7 New and Emerging Techniques/Models/Technologies 330
15.8 Conclusion 331
15.9 Additional References and Resources 331
References 332
Chapter 16: Electrophysiology of Single Cardiomyocytes: Patch Clamp and Other Recording Methods 334
16.1 Introduction 334
16.1.1 Importance of Ion Channel Function in the Heart 335
16.1.2 Understanding Ion Channel Behavior Through Electrical Analogues 335
16.1.3 Terminology 337
16.2 Apparatus for Single-Cell Recordings 338
16.2.1 Microelectrodes 338
16.2.2 Headstage, Amplifier, and Data Acquisition System 339
16.2.3 Cell and Tissue Baths 341
16.2.4 Microscope, Micromanipulator, and Vibration Isolation Table 341
16.3 Recording Modes 342
16.3.1 Extracellular Recording 342
16.3.2 Intracellular Recording 343
16.3.3 Current Clamp 344
16.3.4 Voltage Clamp 346
16.4 Examples of Experimental Protocols 347
16.4.1 Protocol for Intracellular Recording of Human Cardiac Action Potentials 347
16.4.2 Protocol for Patch Clamp Recording of Ih in hHCN4-Transfected HEK293 Cells 348
16.5 Pitfalls and Troubleshooting 350
16.5.1 Tissue and Cell Viability 351
16.5.2 Microelectrodes 351
16.5.3 Electrical Noise 351
16.6 Emerging Technologies for Cellular Electrophysiology 352
References 352
Chapter 17: Invasive Electroanatomical Mapping and Navigation 354
17.1 Introduction 354
17.2 The Use of Electroanatomical Mapping for the Treatment of Atrial Arrhythmias 355
17.2.1 Atrial Tachycardia 355
17.2.2 Atrial Flutter 355
17.2.3 Atrial Fibrillation 355
17.3 The Use of Electroanatomical Mapping for the Treatment of Ventricular Tachycardias 357
17.3.1 Automatic Ventricular Tachycardia 357
17.3.2 Reentrant Ventricular Tachycardia 358
17.4 The Use of Electroanatomical Mapping for the Treatment of Arrhythmias in Patients with Congenital Heart Disease 359
17.5 Types of Electroanatomical Mapping Systems 360
17.5.1 Magnetic-Based Mapping 360
17.5.2 Impedance-Based Mapping 360
17.6 Pitfalls and Troubleshooting 360
References 361
Chapter 18: Cardiac Electrophysiological Imaging: Solving the Inverse Problem of Electrocardiography 362
18.1 Introduction 362
18.2 Moving Dipole Source Imaging 364
18.3 Heart Surface Distributed Source Imaging 365
18.3.1 Epicardial Potential Imaging 365
18.3.2 Heart Surface Activation Imaging 366
18.4 Three-dimensional Source Imaging 368
18.4.1 Inverse Estimation of 3D Dipole Distribution 369
18.4.2 Heart Model-Based 3D Activation Imaging 370
18.4.3 Physical Model-Based 3D Activation Imaging 372
18.5 Imaging Cardiac Sources from Intracavitary Recordings 374
18.6 Discussion 375
References 376
Chapter 19: Traditional Electrophysiological Mapping 379
19.1 Introduction 379
19.2 Description of Apparatus 380
19.2.1 Electrode Catheters 380
19.2.2 Recording Apparatus 380
19.2.3 Stimulation Apparatus 381
19.3 Basic Mechanisms of Common Tachycardia 381
19.3.1 Reentry 381
19.3.2 Automaticity 382
19.3.3 Triggered Activity 383
19.4 Activation Sequence Mapping 383
19.4.1 Local Electrogram Morphology 384
19.4.2 Sinus Rhythm Mapping 387
19.5 Pace Mapping 387
19.6 Entrainment 388
19.6.1 End-Entrainment Data 389
19.7 Additional Mapping Maneuvers 393
19.7.1 Node-Refractory Ventricular Pacing During NCT 393
19.7.2 Parahissian Pacing 393
19.8 Pitfalls and Troubleshooting 396
19.9 Summary 396
References 397
Chapter 20: Multi-channel System for Analysis of Cardiac Rhythmicity and Conductivity In Vitro 398
20.1 Introduction 398
20.2 Multi-channel System 400
20.2.1 Hardware 400
20.2.2 Data Acquisition and Analysis 400
20.2.3 Vibration Isolation and Noise Reduction 401
20.3 Rhythmicity of Cultured Cardiomyocytes 402
20.3.1 HL-5 Cells 403
20.3.2 Neonatal Rat Cardiomyocytes 404
20.3.3 Cardiomyocytes Derived from Stem Cells 406
20.3.4 Myocardial Tissue Slices 406
20.3.5 Biopacing Assessment 407
20.3.6 Pharmacological Effects 409
20.4 Cardiac Electrical Conductivity In Vitro 411
20.4.1 Conductivity Measurement 411
20.4.2 Creation of Conduction Block 411
20.4.3 Cardiac Fibrous Cells for Conduction Repair 413
20.4.4 Conduction Repair by Stem Cells 416
20.5 Summary 417
References 418
Chapter 21: Cardiac CT/MRI Imaging for Electrophysiology 421
21.1 Introduction 421
21.2 Intracardiac Echocardiography 422
21.3 Computed Tomography 424
21.3.1 Ablation of Atrial Fibrillation 424
21.3.2 Atrial Flutter Ablation 427
21.3.3 Biventricular Lead Insertion for Cardiac Resynchronization Therapy 428
21.3.4 Evaluation of Arrhythmogenic Substrate 429
21.4 Magnetic Resonance Imaging 430
21.4.1 Atrial Fibrillation Ablation 430
21.4.2 Ventricular Tachycardia Ablation 431
21.4.3 Subsequent Imaging of Ablation Lesions with Magnetic Resonance Imaging 431
21.4.4 Real-Time Magnetic Resonance Imaging 432
21.5 Fusion Imaging/Multimodal Imaging 433
21.6 Conclusion 434
References 434
Part III Putting It All Together 440
Chapter 22: Introduction to Translational Research 441
22.1 Introduction 441
22.2 Determining the Clinical Problem 443
22.2.1 Cardiac Arrest 443
22.2.2 Heart Failure 443
22.2.3 Atrial Fibrillation 444
22.3 Investigate Mechanisms of Disease 444
22.3.1 Arrhythmias 444
22.3.2 Heart Failure 446
22.4 Define Target and Develop Therapy 446
22.4.1 Cardiac Arrest 447
22.4.2 Heart Failure 447
22.4.3 Atrial Fibrillation 448
22.5 Test Therapy 448
22.5.1 Cardiac Arrest 449
22.5.2 Heart Failure 449
22.5.2.1 Chronic Myocardial Ischemia 450
22.5.2.2 Dilated Cardiomyopathy 450
22.5.2.3 Other Models of Heart Failure 451
22.5.3 Atrial Fibrillation 451
22.6 Clinical Trials 452
22.6.1 Types of Clinical Trials 452
22.6.2 Phases of Clinical Trials 452
22.7 Conclusion 453
References 454
Chapter 23: Clinical Perspective: Electrophysiology in the Young and Patients with Congenital Heart Disease 456
23.1 Introduction 457
23.2 “Natural History” Issues of Arrhythmias in Young Patients 457
23.2.1 Fetal and Newborn Arrhythmias 457
23.2.2 Arrhythmia Under One Year 459
23.2.3 Recurrent and Onset of SVT 459
23.2.4 Late Childhood and Early Adulthood: the Effects of Postoperative Anatomy and Physiology 460
23.2.5 Arrhythmia and CHD in Middle Aged and Older Patients 464
23.2.6 Summary of “Natural History” Aspects 466
23.3 Antiarrhythmic Drug Therapies in Young Patients 466
23.3.1 Pharmacokinetics of AADs in Pediatrics 467
23.3.2 Important Clinical Considerations for AAD Administration in Pediatric and CHD Patients 467
23.4 Clinical Use and Indications for Interventions in the Young 468
23.4.1 Catheter Ablation 468
23.4.2 Pacemaker Implantation 469
23.4.3 Implantable Cardiac Defibrillators 470
23.4.4 Cardiac Resynchronization Therapies 471
23.5 Looking Ahead: Cardiac Rhythm, Device Therapies, and Sudden Cardiac Death in the Adult Population with CHD 472
23.6 Putting It All Together 473
References 474
Index 477
| Erscheint lt. Verlag | 11.9.2010 |
|---|---|
| Zusatzinfo | XIV, 492 p. 172 illus., 93 illus. in color. |
| Verlagsort | New York |
| Sprache | englisch |
| Themenwelt | Medizinische Fachgebiete ► Innere Medizin ► Kardiologie / Angiologie |
| Schlagworte | Arrhythmias • Atrial Fibrillation • cardiac disease • Cardiovascular • electrophysiology • Physiology • tissue |
| ISBN-10 | 1-4419-6658-7 / 1441966587 |
| ISBN-13 | 978-1-4419-6658-2 / 9781441966582 |
| Haben Sie eine Frage zum Produkt? |
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