George Edward Billman

Novel Therapeutic Targets for Antiarrhythmic Drugs

• Gebundenes Buch

Produktbeschreibung

This book provides a comprehensive overview of several promisingnovel drug targets and approaches against arrhythmias, withparticular emphasis placed on malignant ventricular arrhythmias.The individual chapters address a single treatment strategy writtenby a leading expert on the chapter - including arrhythmiamechanisms, kinase inhibitors, calcium and potassium channeltargets, and atrial selective drugs.

Produktdetails

• Verlag: Wiley & Sons
• 1. Auflage
• Seitenzahl: 608
• Erscheinungstermin: 1. Januar 2010
• Englisch
• Abmessung: 240mm x 161mm x 37mm
• Gewicht: 1076g
• ISBN-13: 9780470261002
• ISBN-10: 0470261005
• Artikelnr.: 27869569

Autorenporträt

GEORGE EDWARD BILLMAN is a professor at The Ohio State University. He is currently an Associate Editor of Pharmacology and Therapeutics, an Editor of Experimental Physiology, and on the editorial boards of Journal of Cardiovascular Pharmacology and Journal of Applied Physiology. Dr. Billman has authored over 125 journal articles and has been an invited speaker at twenty national and international scientific meetings. He wrote the chapter "Cardiac Sarcolemmal ATP-Sensitive Potassium Channel Antagonists" in Drug Discovery Handbook (Wiley).

Inhaltsangabe

Acknowledgments. Contributors. 1. Introduction (George E. Billman). 2.
Myocardial K+ Channels: Primary Determinants of Action Potential
Repolarization (Noriko Niwa and Jeanne Nerbonne). 2.1 Introduction. 2.2
Action Potential Waveforms and Repolarizing K+ Currents. 2.3 Functional
Diversity of Repolarizing Myocardial K+ Channels. 2.4 Molecular Diversity
of K+ Channel Subunits. 2.5 Molecular Determinants of Functional Cardiac
Ito Channels. 2.6 Molecular Determinants of Functional Cardiac IK Channels.
2.7 Molecular Determinants of Functional Cardiac Kir Channels. 2.8 Other
Potassium Currents Contributing to Action Potential Repolarization. 3. The
"Funny" Pacemaker Current (Andrea Barbuti, Annalisa Bucchi, Mirko
Baruscotti, and Dario DiFrancesco). 3.1 Introduction: The Mechanism of
Cardiac Pacemaking. 3.2 The "Funny" Current. 3.3 Molecular Determinants of
the If Current. 3.4 Blockers of Funny Channels. 3.5 Genetics of HCN
Channels. 3.6 HCN-Based Biological Pacemakers. 4. Arrhythmia Mechanisms in
Ischemia and Infarction (Ruben Coronel, Wen Dun, Penelope A. Boyden, and
Jacques M.T. de Bakker). 4.1 Introduction. 4.2 Arrhythmogenesis in Acute
Myocardial Ischemia. 4.3 Arrhythmogenesis During the First Week Post MI.
4.4 Arrhythmia Mechanisms in Chronic Infarction. 5. Antiarrhythmic Drug
Classification (Cynthia A. Carnes). 5.1 Introduction. 5.2 Sodium Channel
Blockers. 5.3 Inhibitors of the Fast Sodium Current with Rapid Kinetics
(Vaughan Williams Class Ib). 5.4 Inhibitors of the Fast Sodium Current with
Slow Kinetics (Vaughan Williams Class Ic). 5.5 Inhibitors of Repolarizing
K+ Currents (Vaughan Williams Class III). 5.6 IKur Blockers. 5.7 Inhibitors
of Calcium Channels. 5.8 Inhibitors of Adrenergically-Modulated
Electrophysiology. 5.9 Adenosine. 5.10 Digoxin. 5.11 Conclusions. 6.
Repolarization Reserve and Proarrhythmic Risk (András Varró). 6.1
Definitions and Background. 6.2 The Major Players Contributing to
Repolarization Reserve. 6.3 Mechanism of Arrhythmia Caused By Decreased
Repolarization Reserve. 6.4 Clinical Significance of the Reduced
Repolarization Reserve. 6.5 Repolarization Reserve as a Dynamically
Changing Factor. 6.6 How to Measure the Repolarization Reserve. 6.7
Pharmacological Modulation of the Repolarization Reserve. 6.8 Conclusion.
7. Safety Challenges in the Development of Novel Antiarrhythmic Drugs (Gary
Gintant and Zhi Su). 7.1 Introduction. 7.2 Review of Basic Functional
Cardiac Electrophysiology. 7.3 Safety Pharmacology Perspectives on
Developing Antiarrhythmic Drugs. 7.4 Proarrhythmic Effects of Ventricular
Antiarrhythmic Drugs. 7.5 Avoiding Proarrhythmia with Atrial Antiarrhythmic
Drugs. 8. Safety Pharmacology and Regulatory Issues in the Development of
Antiarrhythmic Medications (Armando Lagrutta and Joseph J. Salata). 8.1
Introduction. 8.2 Basic Physiological Considerations. 8.3 Historical
Considerations. 8.4 Opportunities for Antiarrhythmic Drug Development in
the Present Regulatory Environment. 9. Ion Channel Remodeling and
Arrhythmias (Takeshi Aiba and Gordon F. Tomaselli). 9.1 Introduction. 9.2
Molecular and Cellular Basis for Cardiac Excitability. 9.3 Heart
Failure--Epidemiology and the Arrhythmia Connection. 9.4 K+ Channel
Remodeling in Heart Failure. 9.5 Ca2+ Handling and Arrhythmia Risk. 9.6
Intracellular [Na+] in HF. 9.7 Gap Junctions and Connexins. 9.8 Autonomic
Signaling. 9.9 Calmodulin Kinase. 9.10 Conclusions. 10. Redox Modification
of Ryanodine Receptors in Cardiac Arrhythmia and Failure: A Potential
Therapeutic Target (Andriy E. Belevych, Dmitry Terentyev, and Sandor
Györke). 10.1 Introduction. 10.2 Activation and Deactivation of Ryanodine
Receptors During Normal Excitation-Contraction Coupling. 10.3 Defective
Ryanodine Receptor Function is Linked to Proarrhythmic Delayed
Afterdepolarizations and Calcium Alternans. 10.4 Genetic and Acquired
Defects in Ryanodine Receptors. 10.5 Effects of Thiol-Modifying Agents on
Ryanodine Receptors. 10.6 Reactive Oxygen Species Production and Oxidative
Stress in Cardiac Disease. 10.7 Redox Modification of Ryanodine Receptors
in Cardiac Arrhythmia and Heart Failure. 10.8 Therapeutic Potential of
Normalizing Ryanodine Receptor Function. 11. Targeting Na+/Ca2+ Exchange as
an Antiarrhythmic Strategy (Gudrun Antoons, Rik Willems, and Karin R.
Sipido). 11.1 Introduction. 11.2 Why Target NCX in Arrhythmias? 11.3 When
Do We See Triggered Arrhythmias? 11.4 What Drugs are Available? 11.5
Experience with NCX Inhibitors. 11.6 Caveat--the Consequences on Ca2+
Handling. 11.7 Need for More Development. 12. Calcium/Calmodulin-Dependent
Protein Kinase II (CaMKII)--Modulation of Ion Currents and Potential Role
for Arrhythmias (Dr. Lars S. Maier). 12.1 Introduction. 12.2 Evolving Role
of Ca2+/CaMKII in the Heart. 12.3 Activation of CaMKII. 12.4 Role of CaMKII
in ECC. 12.5 Role of CaMKII for Arrhythmias. 12.6 Summary. 13. Selective
Targeting of Ventricular Potassium Channels for Arrhythmia Suppression:
Feasible or Risible? (Hugh Clements-Jewery and Michael Curtis). 13.1
Introduction. 13.2 Effects of K+ Channel Blockade on APD and
Arrhythmogenesis. 13.3 Conclusions/Future Directions. 14. Cardiac
Sarcolemmal ATP-sensitive Potassium Channel Antagonists: A Class of Drugs
that May Selectively Target the Ischemic Myocardium (George E. Billman).
14.1 Introduction. 14.2 Effects of Myocardial Ischemia on Extracellular
Potassium. 14.3 Effect of Extracellular Potassium on Ventricular Rhythm.
14.4 Effect of ATP-sensitive Potassium Channel Antagonists on Ventricular
Arrhythmias. 14.5 Summary. 15. Mitochondrial Origin of Ischemia-Reperfusion
Arrhythmias (Brian O'Rourke, PHD). 15.1 Introduction. 15.2 Mechanisms of
Arrhythmias. 15.3 Ischemia-Reperfusion Arrhythmias. 15.4 Mitochondrial
Criticality: The Root of Ischemia-Reperfusion Arrhythmias. 15.5 KATP
Activation and Arrhythmias. 15.6 Metabolic Sinks and Reperfusion
Arrhythmias. 15.7 Antioxidant Depletion. 15.8 Mitochondria as Therapeutic
Targets. 16. Cardiac Gap Junctions: A New Target for New Antiarrhythmic
Drugs: Gap Junction Modulators (Anja Hagen and Stefan Dhein). 16.1
Introduction. 16.2 The Development of Gap Junction Modulators and AAPs.
16.3 Molecular Mechanisms of Action of AAPs. 16.4 Antiarrhythmic Effects of
AAPs. 16.5 Site- and Condition-Specific Effects of AAPs; Effects in
Ischemia or Simulated Ischemia. 16.6 Chemistry of AAPs. 16.7 Short Overview
About Cardiac Gap Junctions. 16.8 Gap Junction Modulation as a New
Antiarrhythmic Principle. 17. Novel Pharmacological Targets for the
Management of Atrial Fibrillation (Alexander Burashnikov and Charles
Antzelevitch). 17.1 Introduction. 17.2 Novel Ion Channel Targets for Atrial
Fibrillation Treatment. 17.3 Upstream Therapy Targets for Atrial
Fibrillation. 17.4 Gap Junction as Targets for AF Therapy. 17.5
Intracellular Calcium Handling and AF. 18. IKur, Ultra-rapid Delayed
Rectifier Potassium Current: A Therapeutic Target for Atrial Arrhythmias
(Arun Sridhar and Cynthia A. Carnes). 18.1 Introduction. 18.2 Molecular
Biology of the Kv1.5 Channels. 18.3 IKur as a Therapeutic Target. 18.4
Organic Blockers of IKur. 18.5 Conclusions. 19. Non-Pharmacologic
Manipulation of the Autonomic Nervous System in Human for the Prevention of
Life-Threatening Arrhythmias (Peter J. Schwartz). 19.1 Introduction. 19.2
Sympathetic Nervous System. 19.3 Parasympathetic Nervous System. 19.4
Conclusion. 20. Effects of Endurance Exercise Training on Cardiac Autonomic
Regulation and Susceptibility to Sudden Cardiac Death: A Nonpharmacological
Approach for the Prevention of Ventricular Fibrillation (George E.
Billman). 20.1 Introduction. 20.2 Exercise and Susceptibility to Sudden
Death. 20.3 Cardiac Autonomic Neural Activity and Sudden Cardiac Death.
20.4 b2-Adrenergic Receptor Activation and Susceptibility to VF. 20.5
Effect of Exercise Conditioning on Cardiac Autonomic Regulation. 20.6
Effect of Exercise Training on Myocyte Calcium Regulation. 20.7 Summary and
Conclusions. 21. Dietary Omega-3 Fatty Acids as a Nonpharmacological
Antiarrhythmic Intervention (Barry London and J. Michael Frangiskakis).
21.1 Introduction. 21.2 Fatty Acid Metabolism. 21.3 Cellular Mechanisms.
21.4 Animal Studies. 21.5 Clinical Studies. 21.6 Future Directions.
References. General Index. Index of Drug and Chemical Names.