Cover
Preface
Recommended reading
Sources of illustrations
Acknowledgements
List of abbreviations
About the companion website
Introduction
1. 1 Overview of the cardiovascular system
  1. Blood vessel functions
Anatomy and histology
1. 2 Gross anatomy and histology of the heart
  1. Gross anatomy of the heart (Figure 2.1)
  2. Structure of the myocardium
  3. Coronary circulation (Figure 2.6)
2. 3 Vascular anatomy
  1. The systemic circulation
  2. The pulmonary circulation
  3. The splanchnic circulation
  4. The lymphatic system
3. 4 Vascular histology and smooth muscle cell ultrastructure
  1. Exchange vessel structure
  2. Smooth muscle cell ultrastructure
Blood and body fluids
1. 5 Constituents of blood
  1. Plasma
  2. Blood cells
2. 6 Erythropoiesis, haemoglobin and anaemia
  1. Erythropoiesis
  2. Haemoglobin
  3. Anaemia
3. 7 Haemostasis
  1. Primary haemostasis (Figure 7.1)
  2. Formation of the blood clot (Figures 7.2, 7.3)
  3. Inhibitors of haemostasis and fibrinolysis
  4. Defects in haemostasis
4. 8 Thrombosis and anticoagulants
  1. Thrombosis
  2. Antiplatelet drugs (Figure 8.2)
  3. Anticoagulant drugs (Figure 8.3)
  4. Some laboratory investigations
5. 9 Blood groups and transfusions
  1. Blood groups
  2. The ABO system
  3. Rh groups
  4. Other blood groups
  5. Complications of blood transfusions
  6. Blood storage
Cellular physiology
1. 10 Membrane potential, ion channels and pumps
  1. Resting membrane potential (Figure 10.1)
  2. Ion channels and gating (Figure 10.2)
  3. Ion pumps and exchangers (Figure 10.3)
  4. Ion pumps and membrane potential
2. 11 Electrophysiology of cardiac muscle and origin of the heartbeat
  1. Ventricular muscle action potential (Figure 11.1)
  2. Role of Na⁺–Ca²⁺ exchange
  3. Sinoatrial node
  4. Other regions of the heart (Figure 11.2)
3. 12 Cardiac muscle excitation–contraction coupling
  1. Initiation of contraction
  2. Generation of tension
  3. Relaxation mechanisms
  4. Regulation of contractility
  5. Influence of heart rate
4. 13 Electrical conduction system in the heart
  1. Electrical conduction in cardiac muscle (Figure 13.1)
  2. Conduction pathways in the heart (Figure 13.2)
  3. Abnormalities of impulse generation or conduction (see also Chapters 48–53)
5. 14 The electrocardiogram
  1. Recording the ECG
  2. General features of the ECG (Figure 14.2)
  3. Basic interpretation of the ECG (Figure 14.5)
6. 15 Vascular smooth muscle excitation–contraction coupling
  1. Regulation of contraction by Ca²⁺ and myosin phosphorylation (see shaded area in left cell of Figure 15.1)
  2. Vasoconstricting mechanisms
  3. Effects of IP₃ and diacylglycerol
  4. Ca²⁺ influx mechanisms
  5. Ca²⁺ removal and vasodilator mechanisms (see right cell of Figure 15.1)
Form and function
1. 16 Cardiac cycle
  1. Atrial systole (A)
  2. Ventricular systole
  3. Ejection
  4. Diastole – relaxation and refilling
  5. The pressure–volume loop
  6. Heart sounds and murmurs
2. 17 Control of cardiac output
  1. Filling pressure and Starling’s law of the heart
  2. Importance of Starling’s law
  3. The autonomic nervous system
  4. Venous return and vascular function curves
3. 18 Haemodynamics
  1. Relationships between pressure, resistance and flow
  2. Blood viscosity
  3. Laminar flow
  4. Wall tension
4. 19 Blood pressure and flow in the arteries and arterioles
  1. Factors controlling arterial blood pressure
  2. Blood pressure and flow in the arteries
  3. Arterioles and vascular resistance
5. 20 The microcirculation and lymphatic system and diapedesis
  1. Organization of the microcirculation
  2. Movement of solutes across the capillary wall
  3. The blood–brain barrier
  4. Diapedesis
  5. The lymphatic system
6. 21 Fluid filtration in the microcirculation
  1. Movement of water across the capillary wall
  2. Water filtration and absorption
  3. Pulmonary and systemic oedema
7. 22 The venous system
  1. Venous and arterial compliance
  2. The veins as capacitance vessels
  3. Effects of posture
  4. The skeletal muscle pump
  5. The respiratory pump
  6. Effect of cardiac contraction
8. 23 Local control of blood flow
  1. Autoregulation
  2. Metabolic and reactive hyperaemia
  3. Metabolic factors
  4. Other local mechanisms
9. 24 Regulation of the vasculature by the endothelium
  1. Nitric oxide
  2. Other endothelium‐derived relaxing mechanisms
  3. Endothelium‐derived constricting factors
  4. Endothelium in cardiovascular disease
10. 25 The pulmonary, skeletal muscle and fetal circulations
  1. The pulmonary circulation
  2. The skeletal muscle circulation
  3. The fetal circulation
  4. Circulatory changes at birth
11. 26 The coronary, cutaneous and cerebral circulations
  1. Coronary circulation
  2. Cutaneous circulation
  3. Cerebral circulation
Integration and regulation
1. 27 Cardiovascular reflexes
  1. Intrinsic cardiovascular reflexes
  2. Central regulation of cardiovascular reflexes
2. 28 Autonomic control of the cardiovascular system
  1. The sympathetic system
  2. Effects on the heart
  3. Effects on the vasculature
  4. The parasympathetic system
  5. Effects on the heart
  6. Effects on the vasculature
3. 29 The control of blood volume
  1. Role of sodium and osmoregulation
  2. Control of Na⁺ and blood volume by the kidneys
  3. Antidiuretic hormone in volume regulation
4. 30 Cardiovascular effects of exercise
  1. Effects of exercise on plasma volume
  2. Regulation and coordination of the cardiovascular adaptation to exercise
  3. Systemic effects mediated by autonomic reflexes
  4. Effects of local metabolites on muscle and heart
  5. Effects of training
5. 31 Shock and haemorrhage
  1. Haemorrhagic shock
  2. Immediate compensation
  3. Medium‐ and long‐term mechanisms
  4. Complications and irreversible (refractory) shock
  5. Other types of hypovolaemic shock
  6. Low‐resistance shock
History, examination and investigations
1. 32 History and examination of the cardiovascular system
  1. History
  2. Examination
2. 33 Cardiac imaging
Pathology and therapeutics
1. 34 Risk factors for cardiovascular disease
  1. Modifiable risk factors
  2. Fixed risk factors
  3. Risk scoring in clinical practice
2. 35 β‐blockers, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers and Ca²⁺ channel blockers
  1. β‐adrenoceptor antagonists (β‐blockers)
  2. Angiotensin‐converting enzyme inhibitors and angiotensin 2 receptor blockers
  3. Ca²⁺ channel blockers
3. 36 Hyperlipidaemias
  1. Lipoproteins and lipid transport
  2. Hyperlipidaemias: types and treatments
4. 37 Atherosclerosis
  1. Pathogenesis of atherosclerosis
  2. Oxidized low‐density lipoprotein, macrophages and atherogenesis
  3. Clinical consequences of advanced atherosclerosis
5. 38 Mechanisms of primary hypertension
  1. Vascular remodelling
  2. Secondary hypertension
6. 39 Treatment of hypertension
  1. Definition and implications of hypertension
  2. Diagnosis and general management of hypertension
  3. Drugs used to treat hypertension
  4. Renal effects of vasodilators
7. 40 Stable, microvascular, and vasospastic angina
  1. Stable angina (Figure 40.2)
  2. Microvascular angina (Figure 40.3)
  3. Vasospastic angina (Figure 40.4)
8. 41 Pharmacological management of stable, microvascular and vasospastic angina
  1. Antianginal agents
  2. β‐Adrenergic receptor blockers (see also Chapter 35)
  3. Ca²⁺‐channel blockers (see also Chapter 35)
  4. Nitrovasodilators
  5. Other antianginals
  6. Management of microvascular angina
  7. Management of vasospastic angina
  8. Drugs for secondary prevention of cardiovascular disease
9. 42 Non‐ST segment elevation acute coronary syndromes (NSTE‐ACS)
  1. Pathophysiology of NSTE‐ACS
  2. Management of NSTE‐ACS (Figure 42.3)
10. 43 Coronary revascularisation
  1. Percutaneous coronary intervention (Figure 43.1)
  2. The role of PCI in stable coronary artery disease
  3. Coronary artery bypass grafting (CABG) (Figure 43.2)
  4. PCI vs CABG in stable coronary artery disease
11. 44 Pathophysiology of acute myocardial infarction
  1. Role of thrombosis in MI
  2. Mechanisms and consequences of plaque rupture (Figure 44.1)
  3. Evolution of the infarct (Figure 44.1)
12. 45 ST segment elevation myocardial infarction (STEMI)
  1. Symptoms and signs (Figure 45.1)
  2. Investigations
  3. Immediate management (Figure 45.1)
  4. Subsequent management (Figure 45.1)
  5. Complications of acute myocardial infarction
13. 46 Heart failure
  1. Types of heart failure
  2. Pathophysiology
  3. Consequences of compensation (Figure 46.3)
  4. Myocardial dysfunction and remodelling
14. 47 Treatment of chronic heart failure
  1. ACEI and other vasodilators
  2. β‐receptor blockers
  3. Aldosterone antagonists
  4. Diuretics
  5. Cardiac glycosides
  6. Device therapy in CHF
15. 48 Mechanisms of tachyarrhythmia
  1. Disorders of impulse generation: latent pacemakers and triggered automaticity
  2. Abnormal impulse conduction: re‐entry
  3. The sympathetic nervous system and arrhythmias
16. 49 Atrial fibrillation
  1. Classification of atrial fibrillation
  2. The ventricular rate in atrial fibrillation
  3. Atrial fibrillation and stroke
  4. Management of atrial fibrillation
17. 50 Other supraventricular arrhythmias
18. 51 Ventricular tachyarrhythmias and their non‐pharmacological management
  1. Ventricular rhythm disturbances
19. 52 Pharmacological treatment of tachyarrhythmias
  1. Class I drugs (Figure 52.1.1)
  2. Class II drugs (Figure 52.1.2)
  3. Class III drugs (Figure 52.1.3)
  4. Class IV drugs, adenosine and digoxin (Figure 52.1.4)
20. 53 Conduction system abnormalities and pacing
  1. Atrioventricular block
  2. Bundle branch block
  3. Pacing systems
21. 54 Diseases of the aortic valve
  1. Aortic stenosis
  2. Aortic regurgitation
22. 55 Diseases of the mitral valve
  1. Mitral stenosis (Figure 55.1)
  2. Mitral regurgitation (Figure 55.2)
23. 56 Congenital heart disease
24. 57 Cardiomyopathies and channelopathies
  1. Cardiomyopathies (Figure 57.1)
  2. Channelopathies
25. 58 Pulmonary hypertension
  1. Types of pulmonary hypertension
  2. Pulmonary arterial hypertension
  3. Pathophysiology
  4. Clinical findings and diagnosis
  5. Management
26. 59 Stroke
  1. Stroke signs, symptoms and risk factors
  2. Pathogenesis
  3. Investigations
  4. Acute management
  5. Haemorrhagic stroke
  6. Long‐term management, rehabilitation and secondary prevention
Index
End User License Agreement

List of Illustrations

Chapter 1
1. Figure 1.1 Schematic of the cardiovascular system
Chapter 3
1. Figure 3.1 Typical dimensions for different types of blood vessels
2. Figure 3.2 Arrangement of the major arteries
3. Figure 3.3 Arrangement of the major veins
Chapter 4
1. Figure 4.1 Structure of a typical small muscular artery
2. Figure 4.2 Smooth muscle cell ultrastructure
Chapter 5
1. Figure 5.1 Blood cell centrifugation and PCV
2. Figure 5.2 Composition of plasma
3. Figure 5.3 Protein composition of plasma
4. Figure 5.4 Erythrocytes (red cells)
5. Figure 5.5 Relative proportion of leucocytes (total count ~ 4‐11 x 10⁹ per l...
Chapter 6
1. Figure 6.1 Erythropoiesis and the life cycle of the erythrocyte
2. Figure 6.2 Characteristics of types of anaemia
Chapter 7
1. Figure 7.1 Primary haemostasis, activation of platelets and formation of pla...
2. Figure 7.2 Cell‐based model of clotting
3. Figure 7.3 Fibrin disposition
4. Figure 7.4 Fibrinolysis and active protein C (APC)
Chapter 8
1. Figure 8.1 Risk factors for thrombosis and embolism
2. Figure 8.2 Antiplatelet drugs: action on platelet activation and aggregation...
3. Figure 8.3 Anticoagulant drugs: action on clotting cascade
Chapter 9
1. Figure 9.1 Red cell agglutination in incompatible plasma
2. Figure 9.2 ABO phenotypes
3. Figure 9.3 Safe transfusion?
4. Figure 9.4 Relative distribution of ABO blood types by race
5. Figure 9.5 Distribution of Rhesus groups (Caucasians)
Chapter 10
1. Figure 10.1 Nernst equation and K+ equilibrium potential
2. Figure 10.2 Ion channels and gating
3. Figure 10.3 Ion pumps and exchangers
Chapter 12
1. Figure 12.1 Activation
2. Figure 12.2 Relaxation
3. Figure 12.3 Inotropes
Chapter 13
1. Figure 13.1 Conduction mechanism
2. Figure 13.2 Conduction pathways
3. Figure 13.3 Example ECGS for SA node conductions defects
Chapter 14
1. Figure 14.1 Bipolar limb leads
2. Figure 14.2 Depolarization and the ECG complex
3. Figure 14.3 Precordial (chest) leads
4. Figure 14.4 Hexaxial reference and cardiac axis
5. Figure 14.5 12 lead ECG
6. Figure 14.6 Typical changes associated with MI
Chapter 15
1. Figure 15.1 Vasoconstricting and vasodilating mechanisms of vascular smooth ...
Chapter 17
1. Figure 17.1 Factors affecting cardiac output
2. Figure 17.2 Ventricular function curves
3. Figure 17.3 Vascular function curves
4. Figure 17.4 Guyton's analysis
Chapter 18
1. Figure 18.1 Pressure, resistance and flow in the vascular system.
2. Figure 18.2 Blood pressure and velocity along the vascular system
Chapter 19
1. Figure 19.1 Pressure (above) and velocity (below) in the aorta and arterial ...
2. Figure 19.2 Arterial elasticity and resistance regulate dynamic changes in b...
Chapter 20
1. Figure 20.1 Structure of the microcirculation
2. Figure 20.2 Capillary structure
3. Figure 20.3 Diapedesis
Chapter 21
1. Figure 21.1 Movement of water across the capillary wall is determined by the...
2. Figure 21.2 Flushing of protein from intracellular clefts may influence flui...
Chapter 22
1. Figure 22.1 Determinants of venous pressure and flow
2. Figure 22.2 Venous and arterial compliance
Chapter 23
1. Figure 23.1 Autoregulation
2. Figure 23.2 Mechanisms of autoregulation
3. Figure 23.3 Effects of vasodilating metabolites
Chapter 24
1. Figure 24.1 Regulation of vascular tone by the endothelium
Chapter 25
1. Figure 25.1 Effects of the upright position on pulmonary pressures and blood...
2. Figure 25.2 The fetal circulation
Chapter 26
1. Figure 26.1 Coronary circulation
2. Figure 26.2 Cutaneous circulation
3. Figure 26.3 Cerebral circulation
Chapter 27
1. Figure 27.1 Cardiovascular reflexes regulating blood pressure and volume
Chapter 28
1. Figure 28.1 Autonomic regulation of the cardiovascular system
Chapter 29
1. Figure 29.1 Control of osmolality
2. Figure 29.2 Effect of osmolality, pressure and volume on ADH secretion
3. Figure 29.3 Control of blood volume and pressure
4. Figure 29.4 Pressure natriuresis
Chapter 30
1. Figure 30.1 Changes in haemodynamic parameters with increasing levels of dyn...
2. Figure 30.2 Guyton’s analysis of exercise
3. Figure 30.3 Regulation and coordination of the cardiovascular adaptation to ...
Chapter 31
1. Figure 31.1 Conditions associated with shock
2. Figure 31.2 Treatment of shock (begin within 1 hour)
3. Figure 31.3 Relationship between degree of blood loss and fall in CO and BP...
4. Figure 31.4 Recovery from mild (20%) blood loss
5. Figure 31.5 Effects of severe (45%) blood loss: progressive, reversible and ...
6. Figure 31.6 Cycle of events leading to progressive and irreversible shock
7. Figure 31.7 A classification of shock
Chapter 34
1. Figure 34.1 Relationships between risk factors and cardiovascular disease
Chapter 35
1. Figure 35.1 Mechanisms by which β‐blockers, Ca²⁺ channel blockers and drugs ...
Chapter 36
1. Figure 36.1 Mechanisms of action of drugs used to treat hyperlipidaemias
Chapter 38
1. Figure 38.1 Summary of mechanisms proposed to cause primary hypertension
Chapter 39
1. Figure 39.1 Mechanisms of antihypertensive treatments. Dashed lines indicate...
Chapter 40
1. Figure 40.1 Balance of O2 supply and demand in the myocardium
2. Figure 40.2 Stable angina
3. Figure 40.3 Microvascular angina
4. Figure 40.4 Vasospastic angina
Chapter 41
1. Figure 41.1 Pharmacological management of angina
Chapter 42
1. Figure 42.1 Acute coronary syndromes
2. Figure 42.2 Pathophysiology
3. Figure 42.3 Management of acute coronary syndromes
Chapter 43
1. Figure 43.1 Percutaneous coronary intervention (PCI)
2. Figure 43.2 Coronary artery bypass grafting (CABG)
Chapter 44
1. Figure 44.1 Pathophysiology of acute MI
Chapter 45
1. Figure 45.1 Management of acute MI
Chapter 46
1. Figure 46.1 Underlying causes of heart failure
2. Figure 46.2 Cardiac function curve
3. Figure 46.3 Consequences of left ventricular failure due to ischaemic heart ...
4. Figure 46.4 Role of neurohumoral mechanisms in progression of heart failure...
Chapter 47
1. Figure 47.1 Mechanisms of drugs used to treat chronic heart failure
Chapter 48
1. Figure 48.1 Mechanisms of early and delayed afterdepolarisations
2. Figure 48.2 Mechanism of Wolff‐Parkinson‐White syndrome
3. Figure 48.3 Mechanism of re‐entry in myocardial scar border zone
4. Figure 48.4 Mechanism of functional re‐entry
Chapter 49
1. Figure 49.1 12 lead ECG showing rate‐controlled atrial fibrillation
2. Figure 49.2 Management of atrial fibrillation
Chapter 50
1. Figure 50.1 Lead II of the 12 lead ECG showing atrial ectopy
2. Figure 50.2 Lead II of the 12 lead ECG showing atrial tachycardia
3. Figure 50.3 Lead II of the 12 lead ECG showing atrial flutter
4. Figure 50.4 Atrioventricular nodal re‐entrant tachycardia
5. Figure 50.5 Lead II of the 12 lead ECG showing two complexes with ventricula...
6. Figure 50.6 Lead V4 of the 12 lead ECG showing pre‐exited atrial fibrillatio...
Chapter 51
1. Figure 51.1 Ventricular ectopics
2. Figure 51.2 Monomorphic ventricular tachycardia
3. Figure 51.3 Polymorphic ventricular tachycardia
4. Figure 51.4 Brugada
5. Figure 51.5 Ventricular fibrillation
Chapter 52
1. Figure 52.1 Antiarrhythmic drugs
Chapter 53
1. Figure 53.1 Complete heart block – ventricular escape
2. Figure 53.2 Left bundle branch block
3. Figure 53.3 Right bundle branch block
Chapter 54
1. Figure 54.1 Aortic stenosis
2. Figure 54.2 Aortic regurgitation
Chapter 55
1. Figure 55.1 Mitral stenosis
2. Figure 55.2 Mitral regurgitation
Chapter 57
1. Figure 57.1 Cardiomyopathies
2. Figure 57.2 Cardiac action potentials in LQTS and SQTS
Chapter 58
1. Figure 58.1 Nice (2013) classification of pulmonary hypertension
2. Figure 58.2 Pathogenesis of PAH – putative mechanisms
Chapter 59
1. Figure 59.1 Arterial blood supply to the brain
2. Figure 59.2 Lateral aspect of the cerebral hemisphere showing blood supply
3. Figure 59.3 Coronal section of brain showing blood supply
4. Figure 59.4 Stroke symptoms due to arterial occlusion at different sites

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© 2020 John Wiley & Sons Ltd

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Library of Congress Cataloging‐in‐Publication Data
Names: Aaronson, Philip I. (Philip Irving), 1953– author. | Ward, Jeremy P. T., author. |
Connolly, Michelle J., author. Title: The cardiovascular system at a glance / Philip I. Aaronson, Jeremy P.T. Ward, Michelle J. Connolly.
Other titles: At a glance series (Oxford, England)
Description: Fifth edition. | Hoboken, NJ : Wiley‐Blackwell, 2020. | Series: At a glance series | Includes index.
Identifiers: LCCN 2019047663 (print) | LCCN 2019047664 (ebook) | ISBN 9781119245780 (paperback) | ISBN 9781119245742 (adobe pdf) | ISBN 9781119245766 (epub)
Subjects: MESH: Cardiovascular System–anatomy & histology | Cardiovascular Diseases | Cardiovascular Physiological Phenomena | Handbook
Classification: LCC RC667 (print) | LCC RC667 (ebook) | NLM WG 39 | DDC 616.1–dc23
LC record available at https://lccn.loc.gov/2019047663
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List of abbreviations

5‐HT: 5‐hydroxytryptamine (serotonin)

AAA: abdominal aortic aneurysm

ABP: arterial blood pressure

AC: adenylate cyclase

ACE: angiotensin‐converting enzyme

ACEI: angiotensin‐converting enzyme inhibitor/s

ACS: acute coronary syndromes

ADH: antidiuretic hormone

ADMA: asymmetrical dimethyl arginine

ADP: adenosine diphosphate

AF: atrial fibrillation

AMP: adenosine monophosphate

ANP: atrial natriuretic peptide

ANS: autonomic nervous system

AP: action potential

APAH: pulmonary hypertension associated with other conditions

APC: active protein C

APD: action potential duration

aPTT: activated partial thromboplastin time

AR: aortic regurgitation

ARB: angiotensin 2 receptor blocker

ARDS: acute respiratory distress syndrome

AS: aortic stenosis

ASD: atrial septal defect

ATP: adenosine triphosphate

AV: atrioventricular

AVA: arteriovenous anastomosis

AVN: atrioventricular node

AVNRT: atrioventricular nodal re‐entrant tachycardia

AVRT: atrioventricular re‐entrant tachycardia

AVSD: Atrioventricular septal defects

BBB: blood–brain barrier

BP: blood pressure

CABG: coronary artery bypass grafting

CAD: coronary artery disease

CaM: calmodulin

cAMP: cyclic adenosine monophosphate

CCB: calcium‐channel blocker

CE: cholesteryl ester

CETP: cholesteryl ester transfer protein

CFU‐E: colony‐forming unit erythroid cell

cGMP: cyclic guanosine monophosphate

CHB: omplete heart block

CHD: congenital heart disease

CHD: coronary heart disease

CHF: chronic heart failure

CICR: calcium‐induced calcium release

CK‐MB: creatine kinase MB

CMR: cardiac magnetic resonance imaging

CNS: central nervous system

CO: cardiac output

COPD: chronic obstructive pulmonary disease

COX: cyclooxygenase

CPVT: catecholaminergic polymorphic ventricular tachycardia

CRP: C‐reactive protein

CSF: cerebrospinal fluid

CT: computed tomography

CTPA: computed tomography pulmonary angiogram

CVD: cardiovascular disease

CVP: central venous pressure

CXR: chest X‐ray

DAD: delayed afterdepolarization

DAG: diacylglycerol

DAPT: dual antiplatelet therapy

DBP: diastolic blood pressure

DC: direct current

DCM: dilated cardiomyopathy

DCCV: direct current cardioversion

DHP: dihydropyridine

DIC: disseminated intravascular coagulation

DM2: type 2 diabetes mellitus

DSE: dobutamine stress echocardiography

DVT: deep venous/vein thrombosis

EAD: early afterdepolarization

ECF: extracellular fluid

ECG: electrocardiogram/electrocardiograph (EKG)

ECM: extracellular matrix

EDHF: endothelium‐derived hyperpolarizing factor

EDP: end‐diastolic pressure

EDRF: endothelium‐derived relaxing factor

EDTA: ethylenediaminetetraacetic acid

EDV: end‐diastolic volume

EET: epoxyeicosatrienoic acid

EnaC: epithelial sodium channel

eNOS: endothelial NOS

ERP: effective refractory period

ESR: erythrocyte sedimentation rate

FDP: fibrin degradation product

GP: glycoprotein

GPI: glycoprotein inhibitor

GTN: glyceryl trinitrate

Hb: haemoglobin

HCM: hypertrophic cardiomyopathy

HDL: high‐density lipoprotein

HEET: hydroxyeicosatetraenoic acid

HMG‐CoA: hydroxy‐methylglutanyl coenzyme A

hPAH: heritable pulmonary arterial hypertension

HPV: hypoxic pulmonary vasoconstriction

HR: heart rate

IABP: intra‐aortic balloon pump

ICD: implantable cardioverter defibrillator

IDL: intermediate‐density lipoprotein

Ig: immunoglobulin

IML: intermediolateral

iNOS: inducible NOS

INR: international normalized ratio

IP₃: inisotol 1,4,5‐triphosphate

iPAH: idiopathic pulmonary arterial hypertension

ISH: isolated systolic hypertension

IVUS: intravascular ultrasound

JVP: jugular venous pressure

LA: left atrium

LBBB: left bundle branch block

LDL: low‐density lipoprotein

LITA: left internal thoracic artery

LMWH: low molecular weight heparin

L‐NAME: L‐nitro arginine methyl ester

LPL: lipoprotein lipase

LQT: long QT

LV: left ventricle/left ventricular

LVAD: left ventricular assist device

LVH: left ventricular hypertrophy

MABP: mean arterial blood pressure

MCH: mean cell haemoglobin

MCHC: mean cell haemoglobin concentration

MCV: mean cell volume

MI: myocardial infarction

MLCK: myosin light‐chain kinase

mPAP: mean pressure in the pulmonary artery

MR: mitral regurgitation

MRI: magnetic resonance imaging

MS: mitral stenosis

MW: molecular weight

NCX: Na⁺–Ca²⁺ exchanger

NK: natural killer

NO: nitric oxide

NOS: nitric oxide synthase

nNOS: neuronal nitric oxide synthase

NSAID: non‐steroidal anti‐inflammatory drug

NSCC: non‐selective cation channel

NSTEMI: non‐ST segment elevation myocardial infarction

NTS: nucleus tractus solitarius

NYHA: New York Heart Association

OCT: optical coherence tomography

PA: postero‐anterior

PA: pulmonary artery

PAH: pulmonary arterial hypertension

PAI‐1: plasminogen activator inhibitor‐1

PCI: percutaneous coronary intervention

PCV: packed cell volume

PD: potential difference

PDA: patent ductus arteriosus

PDE: phosphodiesterase

PE: pulmonary embolism

PGE₂: prostaglandin E₂

PGI₂: prostacyclin

PH: pulmonary hypertension

PI3K: phosphatidylinositol 3‐kinase

PKA: protein kinase A

PKC: protein kinase C

PKG: cyclic GMP‐dependent protein kinase

PLD: phospholipid

PMCA: plasma membrane Ca²⁺‐ATPase

PMN: polymorphonuclear leucocyte

PND: paroxysmal nocturnal dyspnoea

PPAR: proliferator‐activated receptor

PRU: peripheral resistance unit

PT: prothrombin time

PTCA: percutaneous transcoronary angioplasty

PVC: premature ventricular contraction

PVR: pulmonary vascular resistance

RAA: renin–angiotensin–aldosterone

RBBB: right bundle branch block

RCA: radiofrequency catheter ablation

RCC: red cell count

RGC: receptor‐gated channel

RMP: resting membrane potential

RV: right ventricle/right ventricular

RVLM: rostral ventrolateral medulla

RVOT: right ventricular outflow tract tachycardia

RyR: ryanodine receptor

SAN: sinoatrial node

SBP: systolic blood pressure

SERCA: smooth endoplasmic reticulum Ca²⁺‐ATPase

SK: streptokinase

SMTC: S‐methyl‐L‐thiocitrulline

SOC: store‐operated Ca²⁺ channel

SPECT: single photon emission computed tomography

SR: sarcoplasmic reticulum

STEMI: ST elevation myocardial infarction

SV: stroke volume

SVR: systemic vascular resistance

SVT: supraventricular tachycardia

TAFI: thrombin activated fibrinolysis inhibitor

TAVI: transcatheter aortic valve implantation

TB: tuberculosis

TEE: transthoracic echocardiogram

TF: tissue factor thromboplastin

TFPI: tissue factor pathway inhibitor

TGF: transforming growth factor

TIA: transient ischaemic attack

TOE: transoesophageal echocardiography/echocardiogram

tPA: tissue plasminogen activator

TPR: total peripheral resistance

TRP: transient receptor potential

TXA₂: thromboxane A₂

UA: unstable angina

uPA: urokinase

VF: ventricular fibrillation

VGC: voltage‐gated channel

VLDL: very low density lipoprotein

VSD: ventricular septal defect

VSM: vascular smooth muscle

VT: ventricular tachycardia

VTE: venous thromboembolism

vWF: von Willebrand factor

WBCC: white blood cell count

WPW: Wolff–Parkinson–White

1
Overview of the cardiovascular system

Schematic illustration of the cardiovascular system with the details marked. — **Figure 1.1** Schematic of the cardiovascular system

The cardiovascular system is composed of the heart, blood vessels and blood. In simple terms, its main functions are:

distribution of O₂ and nutrients (e.g. glucose, amino acids) to all body tissues
transportation of CO₂ and metabolic waste products (e.g. urea) from the tissues to the lungs and excretory organs
distribution of water, electrolytes and hormones throughout the body
contributing to the infrastructure of the immune system
thermoregulation.

Blood is composed of plasma, an aqueous solution containing electrolytes, proteins and other molecules, in which cells are suspended. The cells comprise 40–45% of blood volume and are mainly erythrocytes, but also white blood cells and platelets. Blood volume is about 5.5 L in an ‘average’ 70‐kg man.

Figure 1.1 illustrates the ‘plumbing’ of the cardiovascular system.

Blood is driven through the cardiovascular system by the heart, a muscular pump divided into left and right sides. Each side contains two chambers, an atrium and a ventricle, composed mainly of cardiac muscle cells. The thin‐walled atria serve to fill or ‘prime’ the thick‐walled ventricles, which when full constrict forcefully, creating a pressure head that drives the blood out into the body. Blood enters and leaves each chamber of the heart through separate one‐way valves, which open and close reciprocally (i.e. one closes before the other opens) to ensure that flow is unidirectional.

Consider the flow of blood, starting with its exit from the left ventricle.

When the ventricles contract, the left ventricular internal pressure rises from 0 to 120 mmHg (atmospheric pressure = 0). As the pressure rises, the aortic valve opens and blood is expelled into the aorta, the first and largest artery of the systemic circulation. This period of ventricular contraction is termed systole. The maximal pressure during systole is called the systolic pressure, and it serves both to drive blood through the aorta and to distend the aorta, which is quite elastic. The aortic valve then closes, and the left ventricle relaxes so that it can be refilled with blood from the left atrium via the mitral valve. The period of relaxation is called diastole. During diastole aortic blood flow and pressure diminish but do not fall to zero, because elastic recoil of the aorta continues to exert a diastolic pressure on the blood, which gradually falls to a minimum level of about 80 mmHg. The difference between systolic and diastolic pressures is termed the pulse pressure. Mean arterial blood pressure (MABP) is pressure averaged over the entire cardiac cycle. Because the heart spends approximately 60% of the cardiac cycle in diastole, the MABP is approximately equal to the diastolic pressure + one‐third of the pulse pressure, rather than to the arithmetic average of the systolic and diastolic pressures.

The blood flows from the aorta into the major arteries, each of which supplies blood to an organ or body region. These arteries divide and subdivide into smaller muscular arteries, which eventually give rise to the arterioles – arteries with diameters of <100 μm. Blood enters the arterioles at a mean pressure of about 60–70 mmHg.

The walls of the arteries and arterioles have circumferentially arranged layers of smooth muscle cells. The lumen of the entire vascular system is lined by a monolayer of endothelial cells. These cells secrete vasoactive substances and serve as a barrier, restricting and controlling the movement of fluid, molecules and cells into and out of the vasculature.

The arterioles lead to the smallest vessels, the capillaries, which form a dense network within all body tissues. The capillary wall is a layer of overlapping endothelial cells, with no smooth muscle cells. The pressure in the capillaries ranges from about 25 mmHg on the arterial side to 15 mmHg at the venous end. The capillaries converge into small venules, which also have thin walls of mainly endothelial cells. The venules merge into larger venules, with an increasing content of smooth muscle cells as they widen. These then converge to become veins, which progressively join to give rise to the superior and inferior venae cavae, through which blood returns to the right side of the heart. Veins have a larger diameter than arteries and thus offer relatively little resistance to flow. The small pressure gradient between venules (15 mmHg) and the venae cavae (0 mmHg) is therefore sufficient to drive blood back to the heart.

Blood from the venae cavae enters the right atrium and then the right ventricle through the tricuspid valve. Contraction of the right ventricle, simultaneous with that of the left ventricle, forces blood through the pulmonary valve into the pulmonary artery, which progressively subdivides to form the arteries, arterioles and capillaries of the pulmonary circulation. The pulmonary circulation is shorter and has a much lower pressure than the systemic circulation, with systolic and diastolic pressures of about 25 and 10 mmHg, respectively. The pulmonary capillary network within the lungs surrounds the alveoli of the lungs, allowing exchange of CO₂ for O₂. Oxygenated blood enters pulmonary venules and veins and then the left atrium, which pumps it into the left ventricle for the next systemic cycle.

The output of the right ventricle is slightly lower than that of the left ventricle. This is because 1–2% of the systemic blood flow never reaches the right atrium but is shunted to the left side of the heart via the bronchial circulation (Figure 1.1), and a small fraction of coronary blood flow drains into the thebesian veins (see Chapter 2).

Blood vessel functions

Each vessel type has important functions in addition to being a conduit for blood.

The branching system of elastic and muscular arteries progressively reduces the pulsations in blood pressure and flow imposed by the intermittent ventricular contractions.

The smallest arteries and arterioles have a crucial role in regulating the amount of blood flowing to the tissues by dilating or constricting. This function is regulated by the sympathetic nervous system and factors generated locally in tissues. These vessels are referred to as resistance arteries, because their constriction resists the flow of blood.

Capillaries and small venules are the exchange vessels. Through their walls, gases, fluids and molecules are transferred between blood and tissues. White blood cells can also pass through the venule walls to fight infection in the tissues.

Venules can constrict to offer resistance to the blood flow, and the ratio of arteriolar and venular resistance exerts an important influence on the movement of fluid between capillaries and tissues, thereby affecting blood volume.

The veins are thin walled and very distensible, and therefore contain about 70% of all blood in the cardiovascular system. The arteries contain just 17% of total blood volume. Veins and venules thus serve as volume reservoirs, which can shift blood from the peripheral circulation into the heart and arteries by constricting. In doing so, they can help to increase the cardiac output (volume of blood pumped by the heart per unit time), and they are also able to maintain the blood pressure and tissue perfusion in essential organs if haemorrhage (blood loss) occurs.

2
Gross anatomy and histology of the heart

Schematic illustrations of the gross anatomy of the heart, the arrangement of sarcomere lines and bands, arrangement of intercalated disks, the structure of diad, coronary circulation, and the structure of sarcomere with the details.

Gross anatomy of the heart (Figure 2.1)

The heart consists of four chambers. Blood flows into the right atrium via the superior and inferior venae cavae. The left and right atria connect to the ventricles via the mitral (two cusps) and tricuspid (three cusps) atrioventricular (AV) valves, respectively. The AV valves are passive and closed when the ventricular pressure exceeds that in the atrium. They are prevented from being everted into the atria during systole by fine cords (chordae tendineae) attached between the free margins of the cusps and the papillary muscles, which contract during systole. The outflow from the right ventricle passes through the pulmonary semilunar valve to the pulmonary artery, and that from the left ventricle enters the aorta via the aortic semilunar valve. These valves close passively at the end of systole, when ventricular pressure falls below that of the arteries. Both semilunar valves have three cusps.

The cusps or leaflets of the cardiac valves are formed of fibrous connective tissue, covered in a thin layer of cells similar to and contiguous with the endocardium (AV valves and ventricular surface of semilunar valves) and endothelium (vascular side of semilunar valves). When closed, the cusps form a tight seal (come to apposition) at the commissures (line at which the edges of the leaflets meet).

The atria and ventricles are separated by a band of fibrous connective tissue called the annulus fibrosus, which provides a skeleton for attachment of the muscle and insertion of the valves. It also prevents electrical conduction between the atria and ventricles except at the atrioventricular node (AVN). This is situated near the interatrial septum and the mouth of the coronary sinus and is an important element of the cardiac electrical conduction system (see Chapter 13).

The ventricles fill during diastole; at the initiation of the heartbeat the atria contract and complete ventricular filling. As the ventricles contract the pressure rises sharply, closing the AV valves. When ventricular pressure exceeds the pulmonary artery or aortic pressure, the semilunar valves open and ejection occurs (see Chapter 16). As systole ends and ventricular pressure falls, the semilunar valves are closed by backflow of blood from the arteries.

The force of contraction is generated by the muscle of the heart, the myocardium. The atrial walls are thin. The greater pressure generated by the left ventricle compared with the right is reflected by its greater wall thickness. The inside of the heart is covered in a thin layer of cells called the endocardium, which is similar to the endothelium of blood vessels. The outer surface of the myocardium is covered by the epicardium, a layer of mesothelial cells. The whole heart is enclosed in the pericardium, a thin fibrous sheath or sac, which prevents excessive enlargement. The pericardial space contains interstitial fluid as a lubricant.

Structure of the myocardium

The myocardium consists of cardiac myocytes (muscle cells) that show a striated subcellular structure, although they are less organized than skeletal muscle. The cells are relatively small (100 × 20 μm) and branched, with a single nucleus, and are rich in mitochondria. They are connected together as a network by intercalated discs (Figure 2.2), where the cell membranes are closely opposed. The intercalated discs provide both a structural attachment by ‘glueing’ the cells together at desmosomes, and an electrical connection through gap junctions formed of pores made up of proteins called connexons. As a result, the myocardium acts as a functional syncytium, in other words as a single functional unit, even though the individual cells are still separate. The gap junctions play a vital part in conduction of the electrical impulse through the myocardium (see Chapter 13).

The myocytes contain actin and myosin filaments which form the contractile apparatus and exhibit the classic M and Z lines and A, H and I bands (Figure 2.3). The intercalated discs always coincide with a Z line, as it is here that the actin filaments are anchored to the cytoskeleton. At the Z lines the sarcolemma (cell membrane) forms tubular invaginations into the cells known as the transverse (T) tubular system. The sarcoplasmic reticulum (SR) is less extensive than in skeletal muscle and runs generally in parallel with the length of the cell (Figure 2.4). Close to the T tubules the SR forms terminal cisternae that with the T tubule make up diads (Figure 2.5), an important component of excitation–contraction coupling (see Chapter 12). The typical triad seen in skeletal muscle is less often present. The T tubules and SR never physically join, but are separated by a narrow gap. The myocardium has an extensive system of capillaries.

Coronary circulation (Figure 2.6)

The heart has a rich blood supply, derived from the left and right coronary arteries. These arise separately from the aortic sinus at the base of the aorta, behind the cusps of the aortic valve. They are not blocked by the cusps during systole because of eddy currents, and remain patent throughout the cardiac cycle. The right coronary artery runs forward between the pulmonary trunk and right atrium, to the AV sulcus. As it descends to the lower margin of the heart, it divides to posterior descending and right marginal branches. The left coronary artery runs behind the pulmonary trunk and forward between it and the left atrium. It divides into the circumflex, left marginal and anterior descending branches. There are anastomoses between the left and right marginal branches and the anterior and posterior descending arteries, although these are not sufficient to maintain perfusion if one side of the coronary circulation is occluded.

Most of the blood returns to the right atrium via the coronary sinus, and anterior cardiac veins. The large and small coronary veins run parallel to the left and right coronary arteries, respectively, and empty into the sinus. Numerous other small vessels empty into the cardiac chambers directly, including thebesian veins and arteriosinusoidal vessels.

The coronary circulation is capable of developing a good collateral system in ischaemic heart disease, when a branch or branches are occluded by, for example, atheromatous plaques. Most of the left ventricle is supplied by the left coronary artery, and occlusion can therefore be very dangerous. The AVN and sinus node are supplied by the right coronary artery in the majority of people; disease in this artery can cause a slow heart rate and AV block (see Chapters 13 and 14).