New Solutions for the Heart (eBook)

Foreword (by Lawrence H. Cohn) 6
Foreword (by Ernst Wolner) 8
Preface 10
Contents 12
Contributors 14
Part 1 Introduction 18
1: The Changing Population: The Surgeon´s Challenge 19
1.1 Historic Development and Current Trends in Cardiac Surgery 19
1.2 The Rightward Shift of the Age Curve: Representative Examples for Major Procedures 20
1.3 Early Mortality in the 1990s and in 2010 21
1.4 Why Could We Keep the Outcome Similar or Become Even Better? 22
1.4.1 Standardization of Procedures 22
1.4.2 Training 23
1.4.3 Partners 23
1.5 More Work To Do: What Is Next? 24
1.5.1 Bi-Directional Education 24
1.5.2 New Concepts 25
1.6 Summary 26
References 26
Part 2 Fundamentals 29
2: Fundamentals of the Past: Cardioplegia: The First Period Revisited 30
2.1 Historical Overview 30
2.1.1 Background and Definitions 30
2.1.2 Birth and Burial 32
2.1.3 Survival and Success 32
2.1.3.1 Bretschneider and Söndergaard 33
2.1.3.2 International Reawakening 34
2.1.3.3 British Rediscoveries 36
2.1.4 Status After 25 Years 37
2.2 Concepts and Issues 37
2.2.1 Energy, Metabolism and Recovery from Ischemia 38
2.2.1.1 Rescucitation Time 38
2.2.1.2 The Stone Heart Challenge 39
2.2.2 Hypothermia: The Second Component of Protection 40
2.2.2.1 Hypothermia on Its Own 40
2.2.2.2 Hypothermia Plus Cardioplegia 41
2.2.2.3 Hypothermic Injury 42
2.2.3 Calcium Control 42
2.2.3.1 Calcium Takes Centre Stage 42
2.2.3.2 Cardioplegia and the Calcium Paradox 43
2.2.3.3 Ionic Interactions and Calcium Control 43
2.2.4 Reperfusion 46
2.2.5 Blood as Cardioplegic Vehicle 47
2.3 Summary and Closing Remarks 49
References 50
3: Sites of Injury: Myocyte 56
3.1 Introduction 56
3.2 Ischaemic Heart Disease 56
3.2.1 Metabolic Effects of Ischaemia Reperfusion 57
3.2.2 Ionic Effects of Ischaemia-Reperfusion 57
3.2.2.1 Cytoplasmic Effects 57
3.2.2.2 Mitochondria Effects 59
3.2.3 Oxidative Injury During Ischaemia-Reperfusion 60
3.3 Ventricular Pressure Overload and Hypertrophy 63
3.3.1 Myocyte Signalling Pathway Changes 63
3.3.2 Myocyte Metabolic Changes 64
3.4 Cardioprotection During Surgery 65
3.4.1 Endogenous Protection: Preconditioning and Postconditioning 65
3.5 Conclusions 67
References 67
4: Sites of Injury: The Endothelium 71
4.1 Introduction 71
4.2 Endothelial Cell Activation 72
4.2.1 Quiescent Endothelium 72
4.2.2 Acutely Inflamed Endothelium 72
4.2.3 Chronically Inflamed Endothelium 74
4.2.4 Overlap Between Acute and Chronic Inflammation 75
4.3 Endothelial Dysfunction 75
4.3.1 Endothelial Dysfunction: Definition 75
4.3.2 l-Arginine, NO and Cyclic AMP as Modulators of Vascular Tone 76
4.3.3 Oxidative Stress as the Underlying Mechanism of Endothelial Dysfunction 76
4.4 Endothelial Cell Death 77
4.5 Endothelial Cell Injury in Cardiac Surgery 77
4.5.1 Inflammatory Activation of the Endothelium During Cardioplegia 77
4.5.2 Endothelial Dysfunction and Cardiac Surgery 78
4.5.3 Endothelial Cell Apoptosis and Cardiac Surgery 78
4.6 Summary 79
References 79
Part 3 Special Focus 84
5: Intraoperative Protection of the Myocardium: Effects of Age and Gender 85
5.1 Background 85
5.1.1 Myocardial Protection in the Aged 85
5.1.2 Myocardial Ischemia/Reperfusion Injury 86
5.1.3 Apoptosis in Myocardial Ischemia/Reperfusion Injury 87
5.1.4 Necrosis in Myocardial Ischemia/Reperfusion Injury 88
5.1.5 Morphological Alterations in Ischemia/Reperfusion Injury 88
5.1.6 Mitochondrial Alterations in Ischemia/Reperfusion Injury 90
5.2 Cardioprotection 92
5.3 Effects of Age and Gender in Ischemia/Reperfusion Injury 95
5.4 Decreased Efficacy of Cardioprotection in the Aged Female 96
5.5 Female Age and the Role of Estrogen 96
5.6 Future Directions for the Amelioration of Ischemia/Reperfusion Injury 97
5.7 Conclusion 98
References 98
6: Protection of the Right Heart 105
6.1 Introduction 105
6.2 Physiology of the Right Ventricle 106
6.3 Pathophysiology of Right Heart Failure 107
6.3.1 Effects of an Elevation of Right Ventricular Afterload 107
6.3.2 Ventricular Interdependence 110
6.3.3 Vicious Cycle of Auto-Aggravation 111
6.3.4 Right Ventricular Infarction 111
6.4 Diagnosis of Right Heart Failure 112
6.4.1 Pulmonary Catheter 112
6.4.2 Echocardiography 112
6.5 Treatment Options: Protection Strategies 113
6.5.1 Treatment of Right Ventricular Infarction 113
6.5.2 Fluid Management 113
6.5.3 Systemic Vasodilators 114
6.5.4 Inhaled Vasodilators 114
6.5.5 Inotropes 114
6.5.6 Vasopressors 115
6.5.7 Novel Protective Strategies: Do They Already Exist? 116
6.6 Conclusions 116
References 117
7: Protection of the Failing Heart 120
7.1 Background and Definition 120
7.2 The Surgeon´s Challenge 121
7.3 Development of HF 121
7.3.1 LaPlaces Law 121
7.3.2 Pressure and Volume Overload 122
7.4 Consequences of HF 122
7.4.1 Vascular Dysfunction 122
7.4.2 Neurohumoral Defense Reaction 123
7.4.2.1 The Renin-Angiotensin-Aldosterone System 123
7.4.2.2 The Endothelin System 123
7.4.2.3 Systemic and Local Inflammation 124
7.4.3 Additional Factors Affecting NO Bioavailability, Myocardial Perfusion and Contractility 124
7.4.3.1 Reduction of Shear Stress 124
7.4.3.2 Geometrical Changes of the Ventricle 125
7.5 Evidence that Revascularization in Patients with HF and Coronary Artery Disease is Useful 125
7.5.1 Theoretical Rationale Behind Revascularization 125
7.5.2 Coronary Artery Bypass Graft Surgery Versus Medical Therapy 126
7.5.3 CABG Versus PCI 127
7.5.4 Viability Testing 127
7.6 Evidence that High Risk Valvular Surgery in Patients with HF Improves Outcome 128
7.6.1 Aortic Stenosis and Severely Reduced LV Function 128
7.6.2 Aortic Regurgitation and Severely Reduced LV Function 129
7.6.3 Mitral Valve Surgery and Severely Reduced LV Function 130
7.7 Potential Therapeutic Regimens To Improve Perioperative Myocardial Protection in Patients with HF 131
7.7.1 Optimizing Delivery of Cardioplegia 131
7.7.2 Optimizing Temperature of Cardioplegia 131
7.7.3 Cardioplegia Beyond Myocardial Protection: The Need of Endothelial Protection 132
7.7.4 Mechanical Considerations 134
7.7.5 Perioperative Conditioning of the Heart 135
7.8 Conclusion 136
References 136
8: Protection During Heart Transplantation 141
8.1 Background: Heart Transplantation in the Current Era 141
8.2 Minimising Myocardial Damage 142
8.2.1 Brainstem Death and Donor Organ Injury 143
8.2.1.1 Myocardial Contusion at the Time of Brain Injury 143
8.2.1.2 Haemodynamic Instability and Cushing Response 143
8.2.1.3 Noradrenaline in Donor Resuscitation 144
8.2.1.4 Trauma at Multi-Organ Procurement 145
8.2.1.5 Heart Preservation During the Cold Ischaemic Period 145
8.2.1.6 Safe Storage for Transportation 146
8.2.1.7 Warm Ischaemic Time 147
8.2.1.8 Reperfusion of the Implanted Donor Heart 148
8.3 Results: Outcome of Cardiac Transplantation 148
8.4 Conclusion: Future Perspectives 149
8.5 Summary 149
References 150
Part 4 New Approaches and Technologies 152
9: The Endothelium As Target for Interventions 153
9.1 Introduction 153
9.2 NO Pathway 154
9.2.1 NO Mediated Effects 156
9.3 Endothelium Dysfunction During I/R 156
9.4 Clinical State-of-the-Art to Preserve the Heart During Cardiac Surgery and Transplantation 157
9.5 The Endothelium as Target for Interventions 158
9.5.1 Drugs Influencing NO Homeostasis 158
9.5.1.1 Radical Scavengers 158
9.5.1.2 Calcium Antagonists 160
9.5.1.3 ACE Inhibitors and Bradykinin 160
9.5.1.4 Endothelin Receptor Antagonists 161
9.5.2 Substrates and Cofactors of eNOS 162
9.5.2.1 l-Arginine 162
9.5.2.2 Cofactors of eNOS 163
9.5.3 NO-Releasing Compounds 163
9.6 Discussion 166
9.7 Summary 167
References 168
10: Vascular Effects of Cardioplegic Arrest and Cardiopulmonary Bypass 175
10.1 Introduction 175
10.2 Specific Mediators of Vasomotor Dysfunction 176
10.2.1 Nitric Oxide Synthase 176
10.2.2 Endothelial Derived Hyperpolarizing Factor 177
10.2.3 Cyclooxygenase 177
10.2.4 Pro-Inflammatory Mediators 178
10.2.5 Protein Kinase Pathways 178
10.2.6 Calcium 180
10.3 Clinical Perspective 180
10.4 Conclusion 181
References 182
11: Oxygen Radical Scavengers 187
11.1 Ischemia-Reperfusion Injury 187
11.1.1 Reactive Oxygen Species 188
11.1.2 Reactive Nitrogen Species 190
11.1.3 Calcium 191
11.1.4 Apoptosis 191
11.1.5 Summary 191
11.2 Oxygen Radical Scavengers (Antioxidants) 192
11.2.1 N-acetylcysteine 192
11.2.2 Allopurinol 194
11.2.3 Vitamin E and C 195
11.2.4 Iron Chelators 197
11.2.4.1 Deferoxamine 197
11.2.5 Other Scavengers 198
11.3 Summary 198
References 200
12: New Approaches to Cardioplegia: Alternatives to Hyperkalemia 206
12.1 Introduction 206
12.2 The Induction of Arrest 206
12.2.1 The Physiology of Excitation-Contraction Coupling 207
12.3 Inhibition of the Fast Sodium Channels 209
12.3.1 Shift Resting Em Away from Sodium Activation Threshold 209
12.3.1.1 Extracellular Hyperkalemia (Depolarized Arrest) 209
12.3.1.2 Hyperpolarization/Polarization (Potassium Channel Openers) 211
12.3.2 Direct Blockade of Sodium Channel Activation (Sodium Channel Blockers) 213
12.4 Inhibition of Calcium-Activated Mechanisms 215
12.4.1 Hypocalcemia 215
12.4.2 Direct Blockade of Cell Membrane Calcium Channels (Calcium Channel Blockers) 216
12.4.3 Direct Myofilament Inhibition (Calcium Desensitization) 217
12.5 Inhibition of Multiple Cellular Targets 218
12.5.1 Direct Blockade of Both Sodium and Calcium Channels (eg. Esmolol) 219
12.6 Conclusion 220
References 220
13: Myocardial Protection via the Coronary Venous Route 227
13.1 Introduction 227
13.2 Perioperative Myocardial Protection Via Coronary Sinus 228
13.2.1 The Coronary Veins and Venous Endothelium 229
13.2.1.1 Access to the Coronary Sinus 229
13.2.2 Retrograde Cardioplegia 230
13.3 Peri- and Postinterventional Myocardial Protection: How to Regenerate Ischemic Hearts? 234
13.3.1 Anterograde Intracoronary Cell Transplantation 234
13.3.2 Adjunctive Approaches to Minimize the Reperfusion Injury and Protect Myocardium During Primary PCI: Anterograde Intracoronary Delivery Route 237
13.3.2.1 Adenosine, Nicorandil 237
13.3.2.2 Abciximab, Bivalirudin 238
13.3.2.3 Distal Microcirculatory Protection Devices 238
13.3.2.4 Post-Conditioning 238
13.4 Retrograde Transplantation of Stem Cells and Retroinfusion of Cardioprotective Substances Into Ischemic Myocardium: More than an Alternative Delivery Route 239
13.4.1 Transvenous Intracoronary Route for Cell Transplantation and Gene/Protein Delivery 240
13.4.1.1 Experimental Studies on Transvenous Intracoronary Cell Transplantation 241
13.4.1.2 Clinical Data on Transvenous Intracoronary Cell Transplantation 243
13.4.1.3 Gene and Protein Delivery via Coronary Venous System 243
13.5 Exceptional Role of Pressure in the Hemodynamics of Coronary Sinus Interventions 244
13.5.1 Arterialization of Coronary Veins 245
13.5.2 Pulsatile Cardioplegia 246
13.5.3 Controlled Pressure Elevation in the Coronary Sinus: A Common Denominator of Coronary Sinus Interventions 247
13.6 Conclusion 248
References 249
14: Donor Heart Preservation by Continuous Perfusion 255
14.1 Introduction 255
14.2 Current Concept of Preservation 256
14.3 Rationale of Continuous Machine Perfusion 256
14.4 History 257
14.5 History of Normothermic Oxygenated Blood Perfusion 257
14.6 History of Hypothermic Oxygenated Blood Perfusion 258
14.7 Machine Perfusion Systems 259
14.8 Hypothermic Oxygenated Blood Perfusion 259
14.8.1 Cold Perfusion Concept and Mechanism of Protection 259
14.8.2 Perfusion Route 260
14.8.3 Perfusion Pressure and Flow 260
14.8.4 Perfusate Oxygenation 260
14.8.5 Perfusate Composition 261
14.8.6 Effects of Hypothermic Oxygenated Perfusion Tested in Transplant Models 261
14.8.7 Advantages of Hypothermic Oxygenated Perfusion 262
14.8.8 Disadvantages of Hypothermic Oxygenated Perfusion 262
14.8.9 Clinical Data 263
14.9 Normothermic Oxygenated Blood Perfusion 263
14.9.1 Working Concept and Mechanisms of Protection 263
14.9.2 Perfusion Route 263
14.9.3 Perfusion Pressure and Flow 264
14.9.4 Perfusate Oxygenation 264
14.9.5 Perfusate Composition 264
14.9.6 Effects of Normothermic Oxygenated Perfusion Tested in Transplant Models 265
14.9.7 Advantages of Normothermic Oxygenated Perfusion 265
14.9.8 Disadvantages of Normothermic Oxygenated Perfusion 266
14.9.9 Clinical Data 266
14.10 Conclusion 267
References 268
15: Visualization of Cardioplegia Delivery 275
15.1 Introduction 275
15.2 Myocardial Contrast Echocardiography (MCE) 276
15.2.1 Background 276
15.2.2 Characteristics of Ultrasound Contrast Agents 276
15.2.3 Data Acquisition and Analysis 277
15.2.4 Limitations 279
15.2.5 Future Directions 280
15.3 Near-Infrared Fluorescence Imaging 280
15.3.1 Background 281
15.3.2 Fluorescent Dyes and Their Characteristics 281
15.3.3 Data Acquisition and Analysis 282
15.3.4 Limitations 284
15.4 The Future 285
15.5 Summary 285
References 285
Author Index 289
Subject Index 290
About the Editors 292