ix
Part I Structure, Function and Regulation
The Human Pulmonary Circulation
1 The Human Pulmonary Circulation: Historical Introduction........................... 3
John B. West
Structure and Function of the Pulmonary Circulation
2 Microcirculation of the Lung: Functional and Anatomic Aspects..................... 13
Joan Gil
3 Pulmonary Vascular Development........................................................................ 25
Rosemary C. Jones and Diane E. Capen
4 Pulmonary Vascular Function............................................................................... 61
Robert Naeije and Nico Westerhof
5 Pulmonary Vascular Mechanics............................................................................ 73
Alejandro Roldán-Alzate and Naomi C. Chesler
6 Modeling of the Pulmonary Vasculature.............................................................. 91
Merryn H. Tawhai and Kelly S. Burrowes
7 Metabolic and Clearance Function at the Pulmonary
Microvascular Endothelial Surface in Pulmonary Hypertension...................... 105
Stylianos E. Orfanos and David Langleben
Pulmonary Vasomotor Tone, Vascular Reactivity, and Vascular Permeability
8 The Influence of the Major Vasoactive Mediators
Relevant to the Pathogenesis of Pulmonary Hypertension................................. 117
Margaret R. MacLean and Yvonne Dempsie
9 The Normal Fetal and Neonatal Pulmonary Circulation.................................... 135
Steven H. Abman and Robin H. Steinhorn
10 Excitation–Contraction Coupling and Regulation
of Pulmonary Vascular Contractility.................................................................... 147
Jeremy P.T. Ward and Greg A. Knock
Contents
x Contents
11 Endothelial Regulation of Pulmonary Vascular Tone......................................... 167
Stephen Y. Chan and Joseph Loscalzo
12 Acute Lung Injury: The Injured Lung Endothelium,
Therapeutic Strategies for Barrier Protection, and Vascular Biomarkers........ 197
Eddie T. Chiang, Ting Wang, and Joe G.N. Garcia
Signal Transduction
13 Ion Channels and Transporters in the Pulmonary Vasculature:
A Focus on Smooth Muscle.................................................................................... 223
Amy L. Firth and Jason X.-J. Yuan
14 Receptor-Mediated Signal Transduction and Cell Signaling.............................. 245
Fiona Murray, Jason X.-J. Yuan, and Paul A. Insel
15 Role of Calcium as a Second Messenger in Signaling:
A Focus on Endothelium........................................................................................ 261
Donna L. Cioffi, Christina J. Barry, and Troy Stevens
16 Caveolae and Signaling in Pulmonary Vascular
Endothelial and Smooth Muscle Cells.................................................................. 273
Geerten P. van Nieuw Amerongen, Richard D. Minshall, and Asrar B. Malik
Oxygen Sensing and Reactive Oxygen Specials in the Lung
17 The Chemistry of Biological Gases........................................................................ 287
D. Jeannean Carver and Lisa A. Palmer
18 Role of Oxygen-Derived Species in the Regulation
of Pulmonary Vascular Tone.................................................................................. 301
Michael S. Wolin, Mansoor Ahmad, and Sachin A. Gupte
19 Mitochondrial Reactive Oxygen Species and Redox State
in Pulmonary Vascular O2 Sensing........................................................................ 313
Stephen L. Archer and John J. Ryan
Cell Proliferation and Apoptosis
20 Cellular and Molecular Mechanisms of Pulmonary
Vascular Smooth Muscle Cell Proliferation......................................................... 323
Tamara Tajsic and Nicholas W. Morrell
21 Role of Ca2+ in Vascular Smooth Muscle Gene
Expression and Proliferation................................................................................. 335
Karen M. Lounsbury and Patricia C. Rose
22 Biochemistry and Cellular Mechanisms of Apoptosis
in Vascular Smooth Muscle and Endothelial Cells.............................................. 347
Oliver Eickelberg and Fotini M. Kouri
Coagulation, Thrombosis, and Fibrinolysis
23 The Coagulation Cascade and Its Regulation...................................................... 357
James T.B. Crawley, Jose R. Gonzalez-Porras, and David A. Lane
Contents xi
24 Platelets in Pulmonary Vascular Physiology and Pathology............................... 371
Michael H. Kroll
25 Lysis and Organization of Pulmonary Thromboemboli...................................... 385
Timothy A. Morris and Debby Ngo
Interactions of Pulmonary Vascular Cells with Circulating Blood Cells
26 Interactions of Leukocytes and Coagulation
Factors with the Vessel Wall................................................................................... 399
Scott Visovatti, Takashi Ohtsuka, and David J. Pinsky
27 Interaction of the Plasminogen System with the Vessel Wall.............................. 411
Riku Das and Edward F. Plow
28 Endothelial Apoptosis and Repair in Pulmonary
Arterial Hypertension............................................................................................. 425
Rohit Moudgil, Manoj M. Lalu, and Duncan J. Stewart
The Systemic Circulation in the Lung
29 Bronchial Arterial Circulation in the Human...................................................... 439
Gabor Horvath and Adam Wanner
Part II Methodological Approaches for Research
In vivo and Genetic Animal Models
30 Animal Models of Pulmonary Hypertension........................................................ 453
Jocelyn Dupuis and Norbert Weissmann
31 Transgenic and Gene-Targeted Mouse Models
for Pulmonary Hypertension................................................................................. 459
James D. West
32 Animal Models of Increased Lung Vascular Permeability................................. 471
Sara Hanif Mirza, M. Kamran Mirza, and Asrar B. Malik
Morphological, Functional, and Regulatory Approaches
33 Isolation and Culture of Pulmonary Vascular Smooth
Muscle and Endothelial Cells................................................................................. 485
Carmelle V. Remillard, Ayako Makino, and Jason X.-J. Yuan
34 Conventional Patch Clamp Techniques and High-Throughput Patch
Clamp Recordings on a Chip for Measuring Ion Channel Activity................... 495
Carmelle V. Remillard and Jason X.-J. Yuan
35 Measurement of Pulmonary Vascular Structure
and Pulmonary Blood Distribution by Multidetector-Row
Computed Tomography and Magnetic Resonance Imaging Techniques........... 511
Sara K. Alford and Eric A. Hoffman
xii Contents
Molecular Biological Techniques
36 Quantification of DNA, RNA, and Protein Expression....................................... 525
Fiona Murray, Jason X.-J. Yuan, and Paul A. Insel
37 Gene Cloning, Transfection, and Mutagenesis..................................................... 539
Ellen C. Breen and Jason X.-J. Yuan
38 Approaches for Manipulation of Gene Expression.............................................. 557
Ying Yu and Jason X.-J. Yuan
Genomic, Proteomic and Bioinformatical Approaches
39 Bioinformatics, Genomics, and Functional Genomics: Overview...................... 567
Ali Torkamani, Eric J. Topol, and Nicholas J. Schork
40 Genomic Applications to Study Pulmonary Hypertension................................. 581
Todd M. Bull and Mark W. Geraci
41 Proteomics and Functional Proteomics................................................................. 591
Dayue Darrel Duan
Stem Cells
42 Maintenance, Propagation, and Differentiation of Human
Embryonic Stem Cells and Induced Pluripotent Stem Cells.............................. 613
Zoë L. Vomberg, Megan Robinson, Thomas Fellner, and Karl H. Willert
43 Identification of Adult Stem and Progenitor
Cells in the Pulmonary Vasculature...................................................................... 621
Amy L. Firth, Weijuan Yao, and Jason X.-J. Yuan
44 Differentiation of Embryonic Stem Cells to Vascular Cell Lineages................. 637
Andriana Margariti, Lingfang Zeng, and Qingbo Xu
Clinical Research Approaches
45 Statistics and Clinical Data Analysis: A Reference Guide.................................. 651
Michael C. Donohue, Tanya Wolfson, and Anthony C. Gamst
Part III Pathology and Pathobiology
Hypoxia and Hyperoxia in the Development of Pulmonary Hypertension
46 Hypoxic Pulmonary Vasoconstriction................................................................... 675
E. Kenneth Weir, Jesús A. Cabrera, Douglas A. Peterson,
Saswati Mahapatra, and Zhigang Hong
47 Pathogenic Roles of Ca2+ and Ion Channels in Hypoxia-Mediated
Pulmonary Hypertension....................................................................................... 683
Jian Wang, Dandan Zhang, Carmelle V. Remillard, and Jason X.-J. Yuan
48 Roles of Endothelium-Derived Vasoactive and Mitogenic
Factors in the Development of Chronic-Hypoxia-Mediated
Pulmonary Hypertension....................................................................................... 695
Rajeev Malhotra and Kenneth D. Bloch
Contents xiii
49 Oxygen-Sensitive Transcription Factors and Hypoxia-Mediated
Pulmonary Hypertension....................................................................................... 713
Louise Østergaard, Vinzenz H. Schmid, and Max Gassmann
50 Developmental Regulation of Pulmonary Vascular Oxygen Sensing................. 725
David N. Cornfield
51 Pulmonary Vascular Remodeling by High Oxygen............................................. 733
Rosemary C. Jones and Diane E. Capen
Pulmonary Vasoconstriction and Vascular Remodeling in Pulmonary Hypertension
52 Pulmonary Vascular Remodeling: Cellular
and Molecular Mechanisms................................................................................... 759
Kurt R. Stenmark and Maria G. Frid
53 Carbon Monoxide and Heme Oxygenase in the Regulation
of Pulmonary Vascular Function and Structure.................................................. 779
Stella Kourembanas
54 Shear Stress, Cell Signaling, and Pulmonary Vascular Remodeling................. 787
Shampa Chatterjee and Aron B. Fisher
55 Pulmonary Hypertension and the Extracellular Matrix..................................... 801
Marlene Rabinovitch
56 Role of Progenitor Cells in Pulmonary Vascular Remodeling............................ 811
Kurt R. Stenmark, Susan M. Majka, and Maria G. Frid
57 Receptor Signaling in Pulmonary Arterial Hypertension................................... 825
Patricia A. Thistlethwaite, Robin N. Leathers,
Xioadong Li, and Xiaoxue Zhang
Endothelium and Thrombosis in the Development of Pulmonary Hypertension
58 Role of Endothelium in the Development of Pulmonary Hypertension............. 837
Bryan Ross and Adel Giaid
59 Coagulation and the Vessel Wall in Pulmonary Embolism................................. 851
Irene M. Lang
Pulmonary Edema and Acute Lung Injury
60 Alveolar Epithelial Fluid Transport in Lung Injury........................................... 861
Hans G. Folkesson
61 High-Altitude Pulmonary Edema.......................................................................... 871
Erik R. Swenson
62 Statins and Acute Lung Injury.............................................................................. 889
Amit K. Mahajan and Jeffery R. Jacobson
63 Genomics of Acute Lung Injury and Vascular Barrier Dysfunction................. 899
Roberto F. Machado and Joe G.N. Garcia
xiv Contents
64 Ventilator-Induced Mechanical Stress and Lung Vascular Dysfunction........... 913
Konstantin G. Birukov
Part IV Pulmonary Vascular Diseases
Nomenclature, Classification and Epidemiology of Pulmonary Hypertension
65 Classification of Pulmonary Hypertension: History and Perspectives.............. 937
David B. Badesch
66 Epidemiology of Pulmonary Arterial Hypertension............................................ 943
Jess Mandel and Darren B. Taichman
67 Air Pollution and the Pulmonary Vasculature..................................................... 963
Melissa L. Bates and Rebecca Bascom
Pulmonary Arterial Hypertension
68 Idiopathic Pulmonary Arterial Hypertension...................................................... 979
Jane E. Lewis and Richard N. Channick
69 Genetics of Familial and Idiopathic Pulmonary Arterial Hypertension........... 997
Eric D. Austin, James E. Loyd, and John A. PhillipsIII
70 Pulmonary Arterial Hypertension Related to Scleroderma
and Collagen Vascular Diseases............................................................................. 1011
Paul M. Hassoun
71 Pathology and Management of Portopulmonary Hypertension......................... 1023
Michael J. Krowka
72 Pathobiology and Treatment of Pulmonary
Hypertension in HIV Disease................................................................................. 1033
Michael H. Ieong and Harrison W. Farber
73 Pulmonary Arterial Hypertension Secondary
to Anorexigensand Other Drugs and Toxins........................................................ 1043
Kim Bouillon, Yola Moride, Lamiae Bensouda-Grimaldi,
and Lucien Abenhaim
74 Pulmonary Arterial Hypertension Related to Gaucher’s
Disease, Sarcoidosis, and Other Disorders........................................................... 1061
Judd W. Landsberg and Jess Mandel
Pulmonary Arterial Hypertension in Pediatric Patients
75 Pediatric Pulmonary Hypertension: An Integrated
View from Pediatric Subspecialists....................................................................... 1083
Judy L. Aschner, Candice D. Fike, Eric D. Austin,
Frederick E. Barr, and J. Donald Moore
76 Persistent Pulmonary Hypertension of the Newborn:
Mechanisms and Treatment................................................................................... 1109
Steven H. Abman, Robin H. Steinhorn, and Judy L. Aschner
Contents xv
77 The Pulmonary Circulation in Congenital Heart Disease................................... 1119
Thomas J. Kulik and Mary P. Mullen
78 Pulmonary Hypertension Secondary to Congenital
Systemic-to-Pulmonary (Left-to-Right) Shunts................................................... 1139
Antonio A. Lopes
79 Surgical Evaluation of Congenital-Heart-Disease-Associated
Pulmonary Hypertension....................................................................................... 1153
Clive J. Lewis and Andrew A. Klein
Pulmonary Venous Hypertension
80 Pulmonary Veno-occlusive Disease........................................................................ 1169
Peter F. Clardy and Jess Mandel
81 Left Ventricular Diastolic Heart Function and Pulmonary Hypertension........ 1183
Stuart Rich and Mardi Gomberg-Maitland
Pulmonary Hypertension Associated with Hypoxia and Hypoxemia
82 Pulmonary Hypertension Associated with Chronic
Obstructive Pulmonary Diseases........................................................................... 1189
Norbert F. Voelkel, Catherine Grossman, and Herman J. Bogaard
83 Pulmonary Hypertension Associated with Interstitial Lung Disease................. 1197
Mary E. Strek and Julian Solway
84 High-Altitude Pulmonary Hypertension.............................................................. 1211
Fabiola León-Velarde and Francisco C. Villafuerte
85 Pulmonary Hypertension and Congenital Heart
Defects at High Altitude......................................................................................... 1223
Alexandra Heath de Freudenthal, Franz-Peter Freudenthal Tichauer,
Carmen R. Condori Taboada, and Janne C. Lopes Mendes
Pulmonary Hypertension due to Chronic Thrombotic and/or Embolic Disease
86 Pulmonary Embolism and Deep Vein Thrombosis.............................................. 1231
Paul F. Currier and Charles A. Hales
87 Pulmonary Hypertension Due to Pulmonary
Embolism and Thromboembolic Obstruction of Proximal
and Distal Pulmonary Arteries.............................................................................. 1239
Peter F. Fedullo, Kim M. Kerr, and William R. Auger
88 Risk Factors for Chronic Thromboembolic Pulmonary Hypertension............. 1253
Diana Bonderman and Irene M. Lang
89 Evaluation of Small-Vessel Arteriopathy in Chronic
Thromboembolic Pulmonary Hypertension......................................................... 1261
Nick H. Kim
xvi Contents
90 Hemolytic-Anemia-Associated Pulmonary Hypertension:
Sickle-Cell-Disease- and Thalassemia-Associated
Pulmonary Hypertension..................................................................................... 1269
Elizabeth S. Klings and Mark T. Gladwin
Pulmonary Hypertension due to Disorders Directly Affecting the Pulmonary Vasculature
91 Pulmonary Hypertension Due to Schistosomiasis.............................................. 1283
Ghazwan Butrous and Angela P. Bandiera
92 Pulmonary Hypertension Due to Capillary Hemangiomatosis........................ 1297
Mourad Toporsian, David H. Roberts, and S. Ananth Karumanchi
Right Heart Dysfunction and Pulmonary Hypertension
93 Molecular Basis of Right Ventricular Hypertrophy
and Failure in Pulmonary Vascular Disease....................................................... 1305
Yuichiro J. Suzuki
94 Right Ventricular Dysfunction in Pulmonary Hypertension............................ 1313
Francois Haddad, Mehdi Skhiri, and Evangelos Michelakis
Other Disorders of the Pulmonary Circulation
95 Large Vessel Pulmonary Arteritis....................................................................... 1333
Kim M. Kerr
96 Tumors of the Pulmonary Vascular Bed............................................................. 1343
Eunhee S. Yi
97 Cor Pulmonale....................................................................................................... 1355
Mardi Gomberg-Maitland, Thenappan Thenappan, John J. Ryan,
Ankush Goel, Nicole Cipriani,Aliya N. Husain, Amit Patel,
Savitri E. Fedson, and Stephen L. Archer
98 Pregnancy and Contraception in Patients with Pulmonary
Arterial Hypertension........................................................................................... 1377
Barbara A. Cockrill and Charles A. Hales
Part V Diagnosis and Treatment
Diagnostic Approaches for Pulmonary Vascular Diseases
99 Cardiac Catheterization in the Patient with Pulmonary Hypertension.......... 1387
Christopher Barnett and Ori Ben-Yehuda
100 Imaging of Pulmonary Vascular Diseases........................................................... 1403
Michael A. Bettmann
101 Histological and Pathological Diagnosis of Pulmonary
Hypertension: Pathological Classification of Pulmonary
Vascular Lesions.................................................................................................... 1413
Brian B. Graham, Li Zhang, and Rubin M. Tuder
Contents xvii
102 Echocardiography in Pulmonary Vascular Disease........................................... 1425
Paul R. Forfia
Therapeutic Interventions for Pulmonary Vascular Diseases
103 Calcium Channel Blockers in the Treatment
of Pulmonary Arterial Hypertension.................................................................. 1447
Stuart Rich and Mardi Gomberg-Maitland
104 Prostacyclin and Prostaglandins.......................................................................... 1451
Horst Olschewski
105 Endothelin Receptor Antagonists for the Treatment
of Pulmonary Arterial Hypertension.................................................................. 1465
Victor F. Tapson and Robyn J. Barst
106 Phosphodiesterase Inhibitors in the Treatment
of Pulmonary Hypertension................................................................................. 1477
Lan Zhao, Zhenguo Zhai, John Wharton, and Martin R. Wilkins
107 Nitric Oxide for Children..................................................................................... 1487
Judy L. Aschner, Candice D. Fike, Eric Austin,
J. Donald Moore, and Frederick E. Barr
108 The Serotonin System as a Therapeutic Target
in Pulmonary Hypertension................................................................................. 1501
Serge Adnot
109 Combination Therapy for Pulmonary Arterial Hypertension......................... 1509
Ioana R. Preston and Nicholas S. Hill
110 Thrombolytic and Anticoagulant Therapy for Pulmonary
Embolism and Chronic Thromboembolic Pulmonary Hypertension.............. 1521
Paul F. Currier and Charles A. Hales
111 Nursing Care of Patients with Pulmonary Arterial Hypertension................... 1531
Christine Archer-Chicko
Interventional and Surgical Approaches to Treatment of Pulmonary Vascular Diseases
112 Atrial Septostomy.................................................................................................. 1559
Julio Sandoval, Jorge Gaspar, and Héctor Peña
113 Evaluation of Patients with Chronic Thromboembolic
Pulmonary Hypertension for Pulmonary Endarterectomy.............................. 1567
William R. Auger, Peter F. Fedullo, and Kim M. Kerr
114 Pulmonary Endarterectomy................................................................................ 1575
Michael M. Madani and Stuart W. Jamieson
115 Evaluation of Patients with Pulmonary Hypertension
for Lung Transplantation..................................................................................... 1591
Gordon L. Yung
xviii Contents
116 Lung Transplantation for Pulmonary Hypertension......................................... 1597
Ashish S. Shah and John V. Conte Jr.
117 Living-Donor Lobar Lung Transplantation
for Pulmonary Arterial Hypertension................................................................ 1601
Hiroshi Date and Takahiro Oto
118 Results of Lung Transplantation......................................................................... 1611
Janet R. Maurer
Index................................................................................................................................. 1625