Table Of ContentDELAYED PRECONDITIONING AND ADAPTIVE CARDIOPROTECTION
Developments in
Cardiovascular Medicine
VOLUME 207
The titles published in this series are listed at the end of this volume.
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Contents
Contributors xv
Preface Xl
Acknowledgements xiii
1 Delayed Preconditioning Against Lethal
Ischaemic Injury
G F Baxter and D MYel/on 1
1. Introduction 1
2. Background 2
3. Discovery of Delayed Preconditioning 2
4. Characteristics of Delayed Preconditioning Against Infarction 6
5. Delayed Preconditioning Against Myocyte Injury In Vitro 12
6. Delayed Preconditioning Against Ischaemic Injury in
Other Tissues 13
7. Mechanisms of Delayed Preconditioning 13
8. Triggers of Adaptation in Delayed Preconditioning 15
9. Signal Transduction in Delayed Preconditioning 16
10. Downstream Mediators and Possible Effectors of Protection 18
11. Conclusions 21
References 22
2 Delayed Preconditioning Against Myocardial
Stunning
R Bolli, B Dawn, X-L Tang, Y Qiu, P Ping,
J Zhang and H Takano 29
1. Introduction 29
2. Pathophysiology of Late Preconditioning Against Stunning 30
3. The Preconditioning Stimulus or 'Trigger' of Late PC 32
4. The Signal Transduction Pathways of Late PC 36
5. The Mediator(s) of the Protective Effects of Late PC 37
vi CONTENTS
6. The Nitric Oxide Hypothesis of Late PC 40
7. Conclusions 42
References 43
3 Delayed Preconditioning Against Endothelial
Dysfunction
V Richard, P Beauchamp, N Kaeffer and C Thuillez 47
1. Introduction 47
2. Reperfusion Injury to Endothelial Cells 48
3. Evidence for Delayed Preconditioning of Coronary
Endothelial Cells 52
4. Mechanisms of Delayed Protection 53
5. Mediators of Protection 54
6. Triggers of Protection 56
7. Conclusion 58
References 58
4 Delayed Preconditioning Against Ventricular
Arrhythmias
A Vegh and J R Parratt 63
1. Introduction 63
2. Experimental Background 63
3. From Early to Delayed Protection 65
4. Delayed Protection Against Arrhythmias by Cardiac Pacing 66
5. Time Course and Renewal of Delayed Protection 69
6. Delayed Protection Against Arrhythmias Induced
by Prostacyclin 72
7. Delayed Protection Against Arrhythmias Induced
by Endotoxins 72
8. Delayed Protection Against Arrhythmias Induced
by Catecholamines 73
9. Roles of NO and Bradykinin in Delayed Protection
Against Arrhythmias 75
10. Conclusion 79
References 81
5 Intracellular Signalling Mechanisms in Myocardial
Adaptation to Ischaemia
DKDas 91
1. Introduction 91
2. Stress Adaptation in the Heart 92
CONTENTS vii
3. Signal Transduction Pathways in Adaptation 92
4. Protein Tyrosine Kinase Signalling 92
5. Phospholipase D Signalling 93
6. Protein Kinase C Signalling 96
7. Mitogen Activated Protein Kinases 96
8. p38 MAP Kinase Signalling 97
9. MAPKAP Kinase 2 98
10. Gene Expression 100
11. Conclusion 102
References 103
6 Changes in Cardiac Gene Expression After
Ischaemia and Reperfusion
L V Mayne 111
1. Introduction 111
2. Methodological Considerations 112
3. Pathophysiological Considerations 112
4. Examination of Gene Regulation 113
5. Transcription Factors 114
6. Cytokines and Growth Factors 120
7. Sarcoplasmic Reticulum Calcium Regulating Proteins 124
8. Antioxidants 125
9. Miscellaneous 125
10. Perspective and Conclusion 126
References 127
7 The Heat Shock Response and Tissue Protection
R W Currie and J-C L Plumier 135
1. Introduction 135
2. Heat Shock and HSP70 135
3. Heat Shock, HSP70 and Inducible Cellular Protection in
the Heart 136
4. HSP70 Transgenic Mice and Myocardial Protection 138
5. Function of HSP70 139
6. Inducible Cellular Protection in the Brain 139
7. Other Possibilities 141
8. HSP27 and Endogenous Cellular Protection 142
9. HSP27 in the Heart and Brain 143
10. Conclusions 145
References 146
viii CONTENTS
8 Antioxidant Defences in Myocardial Adaptation
N Yamashita, T Kuzuya and M Hori 155
1. Introduction 155
2. Sublethal Ischaemia-induced Cardioprotection 156
3. Sublethal Heat Stress-induced Cardioprotection 159
4. Exercise and Cardioprotection 164
5. Production of Oxygen Free Radicals and Biphasic
Cardioprotection 165
6. Conclusion 166
References 167
9 Endotoxin, Monophosphoryl Lipid A and Delayed
Cardioprotection
G J Gross 171
1. Introduction 171
2. Effects of MLA and LPS on Myocardial Infarct Size 173
3. Effects ofMLA andLPS on Myocardial Stunning 174
4. Role of Neutrophils in MLA- and LPS-induced Infarct Size
Reduction 176
5. Role of Heat Shock Proteins in MLA- and
LPS-induced Cardioprotection 177
6. Role of ATP-Sensitive Potassium Channels (KATP) in MLA-
induced Infarct Size Reduction 178
7. Role of KATP Channels in MLA-induced Attenuation of
Stunning 180
8. Role of Adenosine in the Cardioprotective Effect of MLA 181
9. Role of NO in MLA-induced Cardioprotection 183
10. Conclusion 183
References 184
10 Adenosine and Delayed Cardioprotection
A Dana, D MYel/on and G F Baxter 189
1. Introduction 189
2. Adenosine as a Trigger of Delayed Preconditioning 190
3. Time Course and Maintenance of Adenosine-induced Delayed
Cardioprotection 193
4. Signal Transduction Mechanisms 196
5. Distal Mediator(s) of Adenosine-induced Delayed Protection 197
6. Conclusion 201
References 202
CONTENTS ix
11 Angina and Cardiac Adaptation
F Ottani, M Galvani and 0 Ferrini 209
1. Introduction 209
2. Preinfarction Angina 209
3. From Experimental Laboratory to Humans 211
4. Pathophysiological Studies 211
5. Retrospective Clinical Studies 214
6. Prospective Clinical Trials 216
7. Preinfarction Angina: Is Preconditioning the Only
Mechanism of Protection? 219
8. Conclusion 221
References 221
Index 225
Preface
The formal recognition by Charles Murry, Robert Jennings and Keith
Reimer in 1986 that myocardium possesses the ability to adapt rapidly to
transient ischaemic stress proved to be the impetus for a remarkable
explosion in experimental and clinical cardiology research. Many who
had previously devoted their valuable time to the investigation of
stategies for protection of the ischaemic myocardium were so impressed
by the potency of this endogenous cardioprotective response that they
opted to examine the phenomenon of myocardial preconditioning in
their own laboratories. The results of these investigations have yielded
an enormous literature during the last decade. The majority of this work
has been devoted to investigating the characteristics and molecular
mechanisms of what is now known as the classic preconditioning
response originally described by Murry, Jennings and Reimer.
In 1993, two reports heralded the recognition of another aspect
of myocardial adaptation to ischaemia, namely a delayed
preconditioning response which we termed the "second window" of
protection. This phenomenon has proved to be of increasing interest
because it represents a further feature of the heart's ability to adapt to
stressful stimuli. During the last five years, a number of studies have
extended the definitions of delayed preconditioning by describing its
ability to protect against a variety of ischaemia-reperfusion pathologies.
Understanding of the potential triggers, cell signalling pathways and
downstream mediators of this sub-acute form of adaptive
cardioprotection has advanced considerably in this period.
In view of a burgeoning literature, reflecting the interest in
delayed preconditioning and related adaptive cardioprotective strategies,
we felt it timely to compile a series of state-of-the-art reviews by those
people who have made significant contributions to the advance of this
field. The chapters contained in this book describe a very rapid advance
in delayed preconditioning reseach, from its molecular basis to potential
clinical relevance. All of the authors, who are internationally recognised
experts, discuss the various aspects of this subject in detail and their
