Cardiac Muscle

In the ever-expanding field of heart research the needs of established re­ searchers, students and general readers can vary considerably, making it difficult therefore to cater for all types of audience within a single volume. The aim of this book has been to provide a comprehensive and up-to-date review of the structure of the heart, including its cell biology. The ultrastructure of the working myocardium and all portions of the conduction system, together with their development, is covered in detail. Also included are chapters on the morphometry of cardiac muscle, the innervation of the heart, cardiac hyper­ trophy and regeneration, and the development of the coronary circulation. A detailed review of cardiac muscle in cell culture is also provided. It is to be hoped that readers, whatever their background, will find the information contained herein useful for their needs. This work was supported by a grant from the National Heart Foundation of Australia. The authors wish to gratefully acknowledge the following people for their invaluable assistance in preparation of the manuscript: Professor Yasuo Uehara, D'r. Takashi· Fujiwara, Dr. Peter Baluk, Dr. Seiji Matsuda and Bill Kaegi for providing unpublished micrographs; Fabian Bowers, Patricia Murphy and Janet Bennett for typing; and Lucy Popadynec, Nella Puglisi, Maggie Mackie, Mary Delafield and Liana Butera for assistance with references and figure preparation. THE AUTHORS Contents A. General Introduction 1 Morphology of Cardiac Muscle 8 B.

A. General Introduction.- B. Morphology of Cardiac Muscle.- I. Light Microscopy of Cardiac Muscle.- II. Ultrastructure of Cardiac Muscle.- 1. Sarcolemma.- 2. Caveolae.- 3. T System.- 4. Intercellular Junctions.- a) Nexus.- b) Desmosome.- c) Fascia Adherens.- 5. Sarcoplasmic Reticulum.- a) Junctional SR.- b) Network (Free) SR.- ?) Central Region of Sarcomere.- ?) Z Disc Region.- ?) Mitochondrial Network SR.- c) Function of SR.- 6. Myofibrillar System.- a) Contractile Elements.- b) Sarcomeric Arrangement of Myofilaments.- c) Myosin ATPase Activity.- d) Myosin Subunits.- e) Z Disc (Band).- 7. Cytoskeleton.- a) Intermediate Filaments.- b) Microtubules.- c) Leptofibrils.- 8. Mitochondria.- 9. Lysosomes.- 10. Atrial Specific Granules.- 11. Other Cell Organelles and Inclusions.- III. Histochemistry.- IV. Extracellular Matrix.- V. Venous Cardiac Muscle.- C. Morphometry of Cardiac Muscle.- I. Methodology.- II. Factors Influencing Morphometric Parameters.- III. Morphometric Parameters in Adult Myocardium.- 1. Myocyte Density and Ratio of Myocytes and Capillaries.- 2. Dimensions of Myocytes.- 3. Composition of the Myocardium.- 4. Composition of Myocytes.- a) Myofibrils.- b) Mitochondria.- c) Nucleus and Matrix.- d) Sarcoplasmic Reticulum and T System.- D. The Conduction System.- I. The Sinoatrial Node.- 1. Location.- 2. Histology.- 3. Ultrastructure of SA Nodal Cells.- a) SA Nodal Cell Size.- b) Myofibrillar System.- c) T System and Sarcoplasmic Reticulum.- d) Mitochondria, Other Organelles and Glycogen.- e) Caveolae.- f) Intercellular Junctions and Basal Lamina.- 4. Transitional Cells.- 5. Intercalated Clear Cells.- 6. Correlation Between Electrophysiological Pacemakers and the Morphological SA Node.- 7. Shifting Locations of the Leading Pacemaker.- 8. Internodal Myocardium.- 9. The Nodal Artery.- II. The Atrioventricular Junctional Tissues.- 1. Location.- 2. Definition of the AV Nodal-Bundle Junction.- 3. Non-Junctional Atrial Myocardium Near the AV Junction.- 4. Converging Preferential Pathways.- 5. Transitional Cell Zone.- 6. The Compact Node.- 7. Individual Variation.- 8. Species Differences.- a) Topography.- b) Connective Tissue.- c) Subdivisions of the AV Junction.- 9. Ultrastructure of the AV Nodal Tissues.- a) Transitional Cells.- b) AV Nodal Cells.- 10. Correlations Between Ultrastructurally- and Electrophysiologically-defined Zones.- 11. Anomalous AV Conduction Pathways.- III. The Ventricular Purkinje System.- 1. Introduction.- a) Distribution.- b) Conduction Velocity.- c) Purkinje Network.- 2. Species Differences.- 3. Ultrastructure of Purkinje Fibres.- a) Purkinje Type I, II and III.- b) T System.- c) Purkinje Myofibrillar Arrangement.- d) Alterations of the Myofibrillar System.- e) Myosin Subunit Composition.- f) Myosin ATPase Activity.- g) Intermediate Filaments.- h) Leptofibrils.- i) Intercellular Junctions.- IV. Histochemistry of Mammalian Conduction Systems.- a) Glycogen.- b) Lipids.- c) Metabolic Enzymes.- V. Non-Mammalian Conduction Systems.- 1. Anatomy of the Non-Mammalian Vertebrate Heart.- 2. Lower Vertebrates.- a) Physiology.- b) Histology.- c) Ultrastructure.- 3. Birds.- a) Sinoatrial Node.- b) Atrioventricular Node.- c) Ventricular Purkinje System.- 4. Phylogenetic Correlations.- E. Innervation of the Heart.- I. Major Nerves Supplying the Heart.- II. Sensory End Formations.- 1. Myelinated Fibres.- 2. Morphological Types of Sensory End Formations.- a) End-Nets.- b) Unencapsulated Endings.- c) Encapsulated Endings.- 3. Ultrastructure of Sensory End Formations.- a) Afferent and Efferent Fibres Supplying End Formations.- b) Cells and Nerve Endings Within the End Formation.- c) Chemoreceptors.- III. Histochemical and Chemical Studies of Efferent Fibres.- 1. Distribution of Parasympathetic Nerves.- a) Comparison of the Four Chambers.- b) Densely-Innervated Atrial Muscle Bundles.- c) Functional Implications of Densely-Innervated Atrial Muscle Bundles.- 2. Distribution of Sympathetic Nerves.- a) Catecholamine Fluorescence Studies.- b) Comparisons with Chemical Studies.- c) Evidence for Different Types of Sympathetic Nerves in the Heart.- 3. Species Differences and Regional Variation of AV Nodal Innervation.- IV. Ultrastructure of Neuromuscular Relationships in the Heart.- 1. Terminology.- a) En Passant.- b) Close Associations.- c) Intimate Contacts.- d) Direct and Diffuse Innervation.- e) Cholinergie and Adrenergic Varicosities.- 2. Innervation of Working Myocardium.- 3. Innervation of the SA Node.- 4. Innervation of the AV Junctional Tissues.- a) Efferent Fibres.- b) Sensory Endings.- c) Species Differences and Regional Variation.- 5. Innervation of the AV Bundle and Purkinje Fibres.- a) Nerve Fibre Density.- b) Efferent Fibres.- c) Sensory Endings.- d) Species Differences and Regional Variation.- 6. An Alternative Concept for the Role of the Intrinsic Innervation of the Heart.- V. Innervation of Non-Mammalian Cardiac Muscle.- 1. Fishes.- a) Parasympathetic Innervation.- b) Sympathetic Innervation and Circulating Catecholamines.- c) Chromaffin Tissue.- d) Morphology of Innervation.- 2. Amphibians and Reptiles.- a) Functional Anatomy.- b) Ultrastructure.- F. Development of Cardiac Muscle.- I. Developmental Stages.- II. Embryonic Heart Formation.- 1. Cardiogenic Crescent.- 2. Development of the Epicardium.- 3. Development of the Endocardium.- III. Formation of the Four-Chambered Heart.- 1. Looping.- 2. Septation.- IV. Development of the Coronary Circulation.- V. Ultrastructure of Developing Cardiac Muscle.- 1. Cytodifferentiation.- 2. Ventricular Myocardium.- a) Myofibrils.- b) Mitochondria.- c) Glycogen.- d) Nucleus and Perinuclear Region.- e) T System.- f) Sarcoplasmic Reticulum.- g) Intercalated Disc.- h) Other Cytoplasmic Constituents.- 3. Mitosis.- 4. Cell Death.- 5. Atrial Myocardium.- VI. Morphometric Changes During the Growth of Myocytes.- 1. General Features.- 2. Dimensions.- 3. Volume Composition of the Myocardium.- 4. Volume Composition of Myocytes.- a) Myofibrils.- b) Mitochondria.- c) Mitochondrial/Myofibrillar Ratio.- d) Matrix.- e) Nucleus.- f) Sarcoplasmic Reticulum.- g) T System.- 5. Correlation of Structure and Function in Developing Myocytes.- G. Development of the Conduction System.- I. Conduction in Embryonic Heart.- 1. ECG of Embryonic Heart.- 2. Preferential Conduction in the AV Canal.- 3. Preferential Conduction in the Ventricular Trabeculae.- II. Development of the Sinoatrial Node.- 1. Development of the Pacemaker.- 2. Cell Coupling in the Absence of Gap Junctions.- 3 Timing of First Appearance and Position of the SA Node.- 4. Cytological Differentiation.- 5. Innervation.- 6. Bilateral Nodal Primordia.- III. Development of the AV Node.- 1. Formation of the AV Node.- 2. Evidence for Species Differences.- 3. The Specialized Ring Tissue Theory.- 4. Innervation.- IV. The Development of the Ventricular Purkinje System.- 1. Differentiation.- 2. Formation of the Purkinje Network.- 3. Theories of Purkinje Fibre Development.- a) Ventriculomyocardium Theory.- b) Specialized Precursor Tissue Theory.- c) The Specialized Ring Tissue Theory.- H. Cardiac Hypertrophy.- I. General Features.- II. Morphological Changes.- III. Morphometric Changes.- IV. Regional Patterns.- I. Regeneration.- J. Cardiac Muscle Cells in Culture.- I. Introduction.- II. Methods of Culture.- 1. Methodology.- a) Monolayer.- b) Synthetic Strand.- c) Cluster.- d) Polystrand.- 2. Culture Medium.- III. Working Myocardium in Culture.- 1. Morphology.- 2. Intercellular Junctions.- 3. Mitosis.- 4. Metabolism.- a) ATP as an Energy Source.- b) Lipid Metabolism.- c) Carbohydrate Metabolism.- d) Amino-Acid Metabolism.- 5. Synthesis of Prostaglandins.- 6. Contractility.- a) Use of Automatic Monitors.- b) Effect of Anaesthetics.- c) Effect of Autonomic Agonists and Antagonists.- d) Effect of Colchicine.- e) Effect of Dibutyryl Cyclic AMP.- 7. Hypoxia.- 8. Electrical Properties.- a) Monolayers and Reaggregates.- b) Changes in Membrane Composition.- 9. Transmembrane Ion Fluxes.- a) Calcium Homeostasis.- b) Calcium Regulation of Cyclic AMP and Beating.- c) Calcium in Myocardial Cell Injury.- d) Other Ion Fluxes.- 10. Effect of Hormones and Drugs.- a) Parathyroid Hormone.- b) Diazepam.- 11. Receptor Modulation.- a) Adrenergic.- b) Cholinergie.- IV. Cellular Interactions.- 1. Nerve — Muscle.- a) Tropic Interactions.- b) Functional Junctions.- 2. Muscle — Non Muscle.- V. Other Cardiac Muscle.- 1. Cardiac Muscle from Blood Vessels.- 2. Conducting System.- References.- Author Index.