01 And 05 Embryology Of Cvs

Development of the Cardiovascular System John M. DeSesso, Ph.D. DABFM, DABFE, CHS-V, FACFEI, Fellow ATS Senior Fellow Noblis Professor of Biochemistry and Molecular & Cellular Biology Georgetown University School of Medicine

Adult Configuration

Position of Heart in the Chest

Position of Heart in the Chest (Concluded)

Anatomy of the Adult Heart

Carlson, Human Embryology and Developmental Biology, 3rd ed (2004)

Review of Early Development

Prior to Implantation the Zygote Receives Nutrition by Diffusion

During Implantation, Most of Zygote is Composed of Extraembryonic Tissue

Langman, Medical Embryology, 4th ed (1981)

Uteroplacental Circulation Begins Before Embryonic Cardiovascular System is Established

Langman, Medical Embryology, 4th ed (1981)

Early Development of the Zygote

DeSesso et al., Am J Med Genet 87: 143-162 (1999)

Induction and Early Differentiation of Cardiovascular System

Signaling Molecules Emanate from Anterior Visceral Endoderm and Prechordal Plate

Carlson, Human Embryology and Developmental Biology, 3rd ed (2004)

Heart Induction Occurs during Both Pre-streak and Ingression Stages

Brand, In Cell Signaling and Growth Factors in Development, Vol. 2, Unsicker and Krieglstein, eds (2006)

Formation of Germ Layers

DeSesso et al., Am J Med Genet 87: 143-162 (1999)

Geospatial Migration and Determination of Cardiac Structures During Ingression

Carlson, Human Embryology and Developmental Biology, 3rd ed (2004)

Early Blood Vessels Form in the Yolk Sac Wall

Langman, Medical Embryology, 4th ed (1981)

Establishing the Blood Vessel Network Vasculogenesi s Angiogenesis

Remodeling Cleaver and Krieg In, Heart Development, Harvey and Rosenthal, eds (1999)

The Heart Tube

Early Development of the Intraembryonic Vascular System

Langman, Medical Embryology, 4th ed (1981)

Cephalocaudal Folding of the Embryo

Langman, Medical Embryology, 4th ed (1981)

Formation of the Heart Tube

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Formation of the Heart Tube (Concluded)

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Formation of Midline Cardiac Tube

Mikawa In, Heart Development, Harvey and Rosenthal, eds (1999)

Ventral View of Early Differentiation of Heart Tube

Moore, The Developing Human, 4th ed (1988)

Folding of Heart Tube: Orientation of Atria

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Superficial and Deep Dissection of Developing Heart Tube

Gilbert, Pictorial Human Embryology (1989)

Superficial and Deep Dissection of Developing Heart Tube (Concluded)

Gilbert, Pictorial Human Embryology (1989)

Atria

Primitive Right and Left Atria Are Formed

Langman, Medical Embryology, 3rd ed (1975)

Development of Interatrial Septum

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Development of the Interatrial Septum (Concluded)

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Overview of Primitive Vascular System

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

The Atria Incorporate Adjacent Structures (dorsal view of the right atrium)

Langman, Medical Embryology, 3rd ed (1975)

Intussusception

The Atria Incorporate Adjacent Structures (ventral view of the left atrium) Pulmonary veins Primitive pulmonary veins

Absorbed pulmonary vein tissue

Primitive left atrium

Right and left pulmonary veins

Four pulmonary veins

Smooth walled portion of left atrium Left atrium Left auricle

Moore, The Developing Human, 4th ed (1988)

Atrioventricular Separation

Atrioventricular Orifices and Endocardial Cushions

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Endocardial Cushions Divide the Atrioventricular Canal

Larsen, Human Embryology, 3rd ed (2001)

Adherons Released by Epimyocardium Induce the Formation of Atrioventricular Mesenchyme

Carlson, Human Embryology and Developmental Biology, 3rd ed (2004)

Ventricles and Outflow Tract

Muscular Interventricular Septum Arises at the Juncture of Bulbus Cordis and Primitive Ventricle

Larsen, Human Embryology, 3rd ed (2001)

The Muscular Interventricular Septum is Formed by Apposition of Adjacent Walls

septum Langman, Medical Embryology, 3rd ed (1975)

Development of Interventricular and Spiral (Aorticopulmonary) Septa

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Development of Interventricular and Spiral (Aorticopulmonary) Septa (Continued)

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Development of Interventricular and Spiral (Aorticopulmonary) Septa (Concluded)

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Anatomy of the Adult Heart

Carlson, Human Embryology and Developmental Biology, 3rd ed (2004)

Formation of Atrioventricular Valves

Sadler, Langman’s Medical Embryology, 8th ed (2000)

Anatomy of the Adult Heart

Carlson, Human Embryology and Developmental Biology, 3rd ed (2004)

Aortic Arches

General Plan for Embryonic Arterial System

Dorsal intersegmental artery

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Differentiation of Aortic Arches

Gilbert, Pictorial Human Embryology (1989)

Fate of Aortic Arches

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

General Plan for Embryonic Arterial System

Dorsal intersegmental artery

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Venous System

Overview of Primitive Vascular System

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Development of Venous System

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Development of Venous System (Continued)

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Development of Venous System (Continued)

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Development of Venous System (Concluded)

Tuchmann-Duplessis and Haegel, Illustrated Human Embryology, Vol. 2 (1972)

Perinatal Circulatory Changes

Fetal Circulation (Human)

Carlson, Human Embryology and Developmental Biology, 3rd ed (2004)

Postnatal Circulation (Human)

Carlson, Human Embryology and Developmental Biology, 3rd ed (2004)

Medial Umbilical Ligaments

Congenital Malformations

Mechanisms Driving Cardiovascular Development

Congenital Malformations: A Major Health Issue • Estimated Incidence Overall – Major & Minor

7%

• Estimated Incidence of Heart Malformations – Among Liveborn – Among Stillbirths

1% 10%

Most Frequently Encountered Cardiovascular Anomalies • • •

Interventricular Septal Defects Persistent Ductus Arteriosus Interatrial Septal Defects

75%

• • •

Coarctation of the Aorta Transposition of Great Vessels Tetralogy of Fallot

20%

Anatomy of the Normal Heart

Sadler, Langman’s Medical Embryology, 8th ed (2000)

Malformations Related to Aberrant Cellular Migration

Sadler, Langman’s Medical Embryology, 8th ed (2000)

Tetralogy of Fallot

Blood Flow

Crouching Posture

Coeur en Sabot

Tetralogy of Fallot

Crouching Posture

Blood Flow

Coeur en Sabot

•Associated with ↓ VEGF •? amelioration by periconceptual multivitamins

Coeur en Sabot Radiographic view of a heart. Note increased transverse diameter, convexity of the inferior line, and elevated, rounded apex. Its form suggests vaguely that of a wooden shoe.

Note the absence of a pulmonary conus and increased angle at the aorticopulmonary window in the upper left heart border (arrow)

Malformations Due to Extracellular Matrix Abnormalities

Moore, The Developing Human, 4th ed (1988)

Membranous Ventricular Septal Defect

Sadler, Langman’s Medical Embryology, 8th ed (2000)

Malformations Caused by Extracellular Matrix Abnormalities (Concluded)

Sadler, Langman’s Medical Embryology, 8th ed (2000)

Malformations Related to Abnormal Blood Flow

Moore, The Developing Human, 4th ed (1988)

Malformations Related to Abnormal Blood Flow (Concluded)

Sadler, Langman’s Medical Embryology, 8th ed (2000)

Malformation Caused by Aberrant Cell Death

Sadler, Langman’s Medical Embryology, 8th ed (2000)

Malformation Related to Abnormal Visceral Situs

Moore, The Developing Human, 4th ed (1988)

Related Literature Carlson, B. M. (2004) Human Embryology and Developmental Biology, 3rd Ed., Ed., Mosby, St. Louis.  

Clark E. B. (1986) Mechanisms in the pathogenesis of congenital cardiac malformations. In: Pierpont ME, Moller JH eds. Genetics of Cardiovascular Disease. Disease. Boston: Martinus Nijhoff Publishing; 3-11.  

Clark E. B. (1992) Growth, Morphogenesis and Function: The Dynamics of Heart Development. In: Moller JH, Neal WA and Lock JE eds. Fetal, Neonatal and Infant Heart Disease. New York: Appleton-CenturyCrofts; 1-17.  

DeSesso, J. M. (2006) Comparative Features of Vertebrate Development, In: Hood R. D, ed. Developmental and Reproductive Toxicology: A Practical Approach, 2nd Ed., Ed., CRC Press, Boca Raton; 147-197.  

Gilbert, S. F. (1997) Developmental Biology, 5th Ed., Sinauer Associates, Sunderland, MA.  

Hamilton, W. J. and H. W. Mossman (1972) Hamilton, Boyd and Mossman’s Human Embryology, 4th Ed., Ed., Williams and Wilkins, Baltimore.  

Harvey, R. P. and N. Rosenthal (1999) Heart Development, Development, Academic Press, San Diego.  

Hebel, R. and M. W. Stromberg (1986) Anatomy and Embryology of the Laboratory Rat, Rat, BioMed Verlag, Worthsee, Germany.  

Larson, W. J. (2001) Human Embryology, 3rd Ed., Ed., Churchill Livingstone, New York.  

O’Rahilly, R. and F. Müller (1992) Human Embryology and Teratology, Teratology, Wiley-Liss, New York.  

Sadler, T. W. (2000) Langman’s Medical Embryology, 8th Ed., Ed., Lippincott Williams & Wilkins, Philadelphia.  

Unsicker, K. and K. Krieglstein (2006) Cell Signaling and Growth Factors in Development, Wiley-VCH, Weinheim, Germany