The Heart - An Elegant Pump: Its Origins and Partners

Contents
Preface
About the Author
Acknowledgements
Chapter 1 Not Just a Pump: Giving Life to Emotion
	The Origin of Heart
	Heart Metaphors
	Heart in European Languages
		Romance and Germanic
		Uralic and Basque languages
	Heart in Non-European Languages
	The Uses of Heart in Ancient Languages
	The Heart in Chinese
	The Heart in Chinese Medicine
	The Heart in Chinese Culture
	Heart Metaphors Expressing Emotion
	Mesopotamia
	The Heart in Mesopotamian Medicine
	Heart in Mesopotamian Culture
	Ancient Egypt
	The Heart in Egyptian Medicine
	Heart in Egyptian Culture
	Heart Metaphors in Ancient Egypt
	The Concept of Heart in 21st Century Culture
	Heart in Religion
	The Physical and Metaphorical Heart: Why We Need Both
	Conclusion
	References
	Appendix I
	Appendix II
	Appendix III
	Appendix IV
	Appendix V
	Appendix VI
Chapter 2 Origins of the Heart
	Starting Life with a Clean Slate
	Development of the Heart
	Genetic Control of Heart Development
		Drosophila Hearts
	Development of Vertebrate Heart
	Evolution of the Four-Chambered Heart
	Molluscs
	Fish
	Amphibians
	Reptiles
	Development of the Four-Chambered Heart in Mammals
		Division of the atrio-ventricular canal
		Division of the primitive atrium
		Division of the primitive ventricle and outflow tract
		Formation of the heart valves
		Mitral and tricuspid valves
		Aortic and pulmonary valves
		Malformations of the heart
		Surgical treatment of cardiac malformations
	Genetics of the Four-Chambered Heart
	Conclusion
	References
Chapter 3 Molecular Motors
	Regulation of the Heart
		External regulation
		Internal regulation
			Frank–Starling response
			The Anrep effect
			Force frequency response
	Structure of the Heart
	Molecular Motor Structure
		Myosin heavy chains
		Myosin light chains
	Origins of Actin and Myosin
		Actin
		Myosin
	Anatomy of Cross Bridge Interaction
		Tropomyosin
		Troponin
		Myosin light chains
		Myosin binding protein-C (MyBP-C)
		Titin
	Operation of the Heart Motor
		Cross bridge interaction
			Activation
			Actin myosin cyclic interaction
			Regulation of the myosin–actin cycle
	Autonomic Regulation of the Heart
		Autonomic control of the molecular motor of the heart
		Sympathetic nerves within the heart
		Adrenergic signalling
	Protein Kinase A Modulation of the Heart’s Motor
		PKA control of the Ca2+ transient
		PKA modulation of actin–myosin cross bridge interaction
	Conclusion
	References
Chapter 4 An Intelligent Pump
	Bio-communication
		Modes of communication
		Resting membrane potential
		Ion pumps
		Osmotic control and electrochemical gradients
		Action potentials
		Regulation of calcium ions
		Ca2+ and action potentials signals
		Origin of Ca2+ signalling
			Ca2+ regulates contraction
		The origin of action potentials
		Voltage-gated ion channels
			The origin of voltage-gated ion channels
			Voltage-gated ion channels in heart cells
		How did action potentials evolve?
		Action potentials in the heart
	Electrical Anatomy of the Heart
		Sinus node and atrial activation
		Atrio ventricular node
		The bundle of His
			Bundle branches
		Cell-to-cell conduction
		Velocity of propagation
		Specialisation of cardiac action potentials
		Ventricular action potentials
			Depolarisation
			Early repolarisation and the early transient outward K+ current (Ito)
			Inward calcium current Ica
			Late repolarisation and outward potassium currents
		Atrial action potentials
		Purkinje fibre action potentials
		Atrioventricular node cells
		Sinus node
		Diastolic depolarisation
			The role of IKf in diastolic depolarisation
			The role of periodic SR Ca2+ in sinus node cells
	Maintaining a Normal Heart Rhythm
		A dominant pacemaker
		Managing multiple pacemaker cells
		Abnormal pacemaker function
			Refractoriness
		Orderly conduction
		The problem of re-entry
	Conclusions
	References
Chapter 5 A Pump for Life: In Good Times and in Bad
	Working Within Its Limitations
		Physiological adaptability
		Circulatory responses to exercises
		Distribution of blood flow during exercise
			Regional blood flow during exercise
	Local Regulation of Muscle Blood Flow
		Direct muscle pump effects
		Vascular conductance
		Haemodynamic forces acting on blood vessels
		Flow-mediated dilatation
		EDRF and nitric oxide
		Transduction of shear stress
	Perfusion of the Heart During Exercise
		Feed-forward control
		Feedback control
		Retrograde conducted response
	Physical Adaptability
		Regulation of heart size
		Hypertrophy
		Pregnancy-induced hypertrophy
		Exercise-induced hypertrophy
		Isometric and isotonic exercise
		Hypertrophy as a compensatory mechanism
		Is exercise-induced hypertrophy harmful?
		Development and regression of hypertrophy
		Exercise hypertrophy in older hearts
		Long-term effects of physiological hypertrophy
	Pathological Hypertrophy
		Pressure overload
		Volume overload
		Hypertrophic cardiomyopathy
		Long-term effects of overload hypertrophy
	Morphology of LVH
		Inter-myocyte connections
		Coronary circulation
		Coronary morphology
		Haemodynamic effects on coronary perfusion
	Heart Failure
		Hypertrophy transition to heart failure
	Maintenance and Regeneration of the Heart
		Servicing the heart
			The ubiquitin-proteasome system
			Autophagy
			Calpain system
		Protein turnover and muscle growth
		Can the heart regenerate?
			Regeneration by proliferation of existing myocytes
			Polyploidy
	Conclusion
	References
Chapter 6 Broken Hearts: Repair and Recovery
	Broken Heart Syndrome: A Heart Metaphor with Cardiac Consequences
	Lonely Hearts
	Heart Attack
	A 20th Century Epidemic
	Heart Attack Symptoms
	Diagnosis
	The Electrocardiogram
	Blood Tests
	Atherosclerosis
	Myocardial Ischaemia
	Coronary Thrombosis
	Acute Coronary Syndromes
	Myocardial Infarction
		Complications of MI
	Sudden Cardiac Death
	Cardiogenic Shock
	Cardiac Rupture
	Evolving Infarction
	Pathophysiology
	Myocardial Response to Injury
	Inflammation
	Inflammation in Myocardial Infarction
	PAMPs and DAMPs
	Pro-inflammatory Phase
	Cytokines and Chemokines
	Endothelial Cells
	Neutrophils
	Monocytes
	Monocyte Functions
	Repair and Proliferative Phase
	New Growth
	Fibroblasts
	Therapeutic Intervention in the Inflammatory Response in MI
	Stem Cell Interventions in MI
	Conclusions
	References
	Appendix I
		Danger associated molecular patterns
	Appendix II
		Pattern recognition receptors
Chapter 7 Roots and Branches
	Evolution of the Circulation
	Coelomic Circulation
	Blood-based Vascular Systems
	Open Circulatory Systems
	Closed Circulatory Systems
	Vertebrates
	Anatomy of the Circulation
	Pulsatile Pumping
	Non-linear Elasticity
	Structure of Arteries
	Invertebrate Arteries
	Microfibrils and Elastic Fibre Assembly
	Resistance Arteries
	Muscular Arteries
	Blood Pressure Regulation
		Vascular remodelling
			Conductive arteries
			Resistance arteries
		Capillary filtration and transport
		Blood brain barrier
		Neurovascular unit
	The Circulation’s Reservoir
		Passive changes in venous capacity
		Active changes in venous capacity
	Conclusions
	References
Chapter 8 Intelligent Tubes
	Introduction
	Intelligent Tubes in the Circulation
	Myogenic Tone
	Smooth Muscle
	Contractile Function
	Length Adaptability
	Smooth Muscle Structure
		Cell structure
		Smooth muscle cytoskeleton
		Intermediate filaments
		Actin–myosin filaments
		Dense bodies
	A Dynamic Cytoskeleton
	Smooth Muscle Contraction
		Actin–myosin configuration in SMCs
		Bi-polar and side-polar myosin
		Actin–myosin interaction in SMCs
		Activation of smooth muscle contraction
	Signalling Pathways Regulating Contraction
	Multiple Interacting Controls
		Vasoactive agonist stimulation
	Mechano-sensing in Blood Vessels
		Flow mediated dilatation
		Stretch induced contraction — Myogenic tone
		Sensing stretch
		Stretch-induced depolarisation
	Evolution of Muscle
	Smooth Muscle Cells are Flexible in Structure and Function
	Actin Binding Proteins
		Smooth muscle tropomyosin
		Caldesmon
		Calponin and PKC mediated contraction
	Tropomyosin: A Master Actin Filament Regulator
	Smooth Muscle Length Adaptability
		Dynamic actin polymerisation
		Dynamic myosin polymerisation
	Conclusions
	References
Chapter 9 Heart and Blood: Co-evolved Intimate Partners
	Introduction
	Composition of Blood
	Transport Medium
	Oxygen Consumption
	Oxidation of the Earth’s Atmosphere
	Photosynthesis
		Atmospheric oxygen and the evolution of complex life forms
	Complex Organisms Needed More Efficient Oxygen Delivery
	Evolution of Oxygen Use
	Oxygen Transport
	Haemocyanins
		The structure of haemocyanins
	Haemerythrins
	Haemoglobin
		Structure of haemoglobins
		Synthesis of haemoglobin
		Haem synthesis
		Globin synthesis
		Regulation of haemoglobin production
	Haemoglobin and Oxygen Transport
		Cooperative and allosteric binding
	In Vivo Modulation of Haemoglobin Oxygen Affinity
		The Bohr effect
		The Haldane effect
		2,3-Bisphosphoglyceric acid
	Evolution of Haemoglobin and Erythrocytes: Matching the Heart and Circulation
	Why Are Capillaries and Erythrocytes of Similar Size?
		Erythrocyte structure, blood viscosity and the heart
		Factors affecting viscosity of blood
		The Fåhræus–Lindqvist effect
	Co-evolution of Erythrocytes and Haemoglobin
	Biconcave Disc Erythrocytes
	Erythrocyte Size, Metabolic Activity and Genome Size
	Diminution of Capillaries and Erythrocytes in Mammals and Bird
	Conclusions
	References
Chapter 10 Preserving the Heart
	Introduction
	Diets Then and Now
	Physical Activity Then and Now
	Tobacco and Alcohol Then and Now
	Cardiovascular Disease Then and Now
	Diabetes Then and Now
	Obesity Then and Now
	Blood Pressure Then and Now
	Impact of Lifestyle Changes on Longevity
	Learning from the Past
	What and How We Eat
	Dietary Modification to Reduce Cardiovascular Disease
		Mediterranean diet
	Individual and Population Dietary Challenges
	Physical Activity and Cardiovascular Health
	Physical Activity Guidelines
	Any Is Good, the More the Better
	Physical Activity for Life
	Tobacco and the Heart
	The Health Burden of Tobacco
	Recollections of an Ex-smoker
	Working Towards a Tobacco-free World
	Alcohol and the Heart
	Can We Drink Safely?
	Summary and Conclusions
	References
Index