Lung Biology in Health & Disease Volume 215 Ventilator-Induced Lung Injury

Introduction......Page 14
Preface......Page 16
Contributors......Page 18
Contents......Page 24
I. Introduction......Page 36
II. Mechanical Forces......Page 37
III. Membrane Signal Transduction......Page 41
IV. Intracellular Signal Transduction......Page 45
V. Conclusion......Page 49
References......Page 50
I. Introduction......Page 56
II. Determinants of Regional Pressure and Volume in Health and Disease......Page 57
III. Micromechanics of the Normal Lung......Page 61
IV. Alveolar Micromechanics in Injury States......Page 64
V. Mechanisms by Which Ventilators Injure Lungs......Page 67
VI. Concluding Remarks......Page 72
References......Page 73
I. Introduction......Page 80
II. The Histology of VILI......Page 81
III. Cellular Stress Failure in Ventilator-Injured Lungs......Page 83
IV. Determinants of PM Tension......Page 85
V. Cell Deformation–Associated PM Remodeling......Page 87
VI. PM Repair......Page 90
VII. Effects of PM Wounding on Gene Expression and Cell Survival......Page 92
References......Page 94
I. Introduction......Page 104
II. Passive Effects of Lung Distention......Page 106
III. Active Endothelial Control of Vascular Permeability......Page 107
References......Page 121
I. Introduction......Page 132
II. Effect of Pulmonary Expansion on the Pulmonary Vascular Tree......Page 133
III. Response of the Endothelial Cell to Shear Forces......Page 135
IV. Interactions Between Airway and Pulmonary Vascular Pressures......Page 136
V. Mechanisms Disrupting the Blood–Gas Barrier......Page 138
VI. Behavior of Airway and Vascular Pressures in Heterogeneous Areas......Page 140
VII. Role of Vascular Pressure and Flow on Genesis of VILI......Page 141
VIII. Effect of Respiratory Rate and Flow on Expression of VILI......Page 142
IX. Cyclic Effect on the Microvascular Environment Induced by Mechanical Ventilation......Page 145
X. Effect of Postalveolar Vascular Pressure on the Development of VILI......Page 146
XI. Potential Clinical Implications......Page 147
XII. Conclusions......Page 148
References......Page 149
I. Introduction......Page 154
II. Acute Pulmonary Edema Consecutive to High-Lung-Volume Ventilation......Page 155
III. Respiratory Mechanics and Severity of VILI......Page 163
IV. Respiratory System PV Curve Changes During Lung Injury......Page 164
V. Improvement of Lung Mechanical Properties and Protection from VILI......Page 178
VI. Clinical Considerations......Page 180
References......Page 182
I. Introduction......Page 192
II. Background......Page 193
III. Introduction to Pulmonary Fluid–Structure Interactions......Page 197
IV. Microscale Fluid–Structure Interactions Leading to VILI......Page 205
V. The Protective Effect of Pulmonary Surfactant......Page 220
VI. Future Directions......Page 228
References......Page 232
I. Introduction......Page 240
II. Ventilator-Induced Lung Inflammation......Page 241
III. Cells Submitted to Mechanical Stress......Page 243
V. Mechanosensing......Page 244
VII. Cyclic Stretch–Induced Cell Activation......Page 246
VIII. Synergy Between Cyclic Stretch and Inflammatory Stimuli......Page 247
IX. Genes Activated by Cyclic Stretch......Page 248
X. Conclusions and Perspectives......Page 250
References......Page 251
I. Introduction......Page 258
II. Mechanical Ventilation of the ALI/ARDS Lung......Page 259
IV. Cytokines and the Pathogenesis of VALI/VILI......Page 260
V. The Role of TNF-α During the Pathogenesis of VALI/VILI......Page 262
VI. The Role of IL-1β During the Pathogenesis of VALI/VILI......Page 270
VII. The Role of IL-6 During the Pathogenesis of VALI/VILI......Page 273
VIII. The Role of IFN-γ During the Pathogenesis of VALI/VILI......Page 274
IX. The Role of IL-10 During the Pathogenesis of VALI/VILI......Page 275
X. The Role of TGF-β During the Pathogenesis of VALI/VILI......Page 276
XI. The Role of Chemokines and Chemokine Receptors During the Pathogenesis of VALI/VILI......Page 277
XII. The Role of CC Chemokines During the Pathogenesis of VALI/VILI......Page 281
XIII. Conclusion......Page 282
References......Page 284
I. Introduction......Page 302
II. Physiological Effects of MV......Page 304
III. Mechanical Strain–Induced Release of Inflammatory Mediators In Vitro......Page 305
IV. Pulmonary and Systemic Release of Inflammatory Mediators in Ex Vivo and In Vivo Models of VILI......Page 306
V. Passage of Mediators from Lung to Bloodstream......Page 308
VII. Bacterial Translocation in MV......Page 310
IX. Pulmonary and Systemic Inflammatory Mediators in VILI in Clinical Studies......Page 311
XI. Conclusions......Page 313
References......Page 314
I. Introduction......Page 320
II. Alveolar Epithelial Sodium Transport......Page 321
III. Alveolar Fluid Reabsorption During VILI......Page 322
References......Page 323
I. Introduction......Page 328
II. Surfactant Depletion and Deactivation......Page 329
III. Toxic Lung Injuries......Page 332
IV. Inflammation and Infection: The Importance of Lung Priming and the Two-Hit Theory......Page 337
VI. Counteracting Previous Lung Injury......Page 341
VII. Clinical Considerations......Page 344
References......Page 345
I. Introduction......Page 350
II. Rationale for Biological Markers of VILI......Page 351
III. Recent Progress in Identifying Biological Markers of VILI......Page 353
IV. Future Approaches to Identifying Markers of VILI......Page 365
V. Summary and Conclusions......Page 368
References......Page 369
I. Introduction—Historical Context......Page 376
II. Hypercapnia—Definitions and Terminology......Page 377
III. Hypercapnia—Physiologic Effects......Page 380
IV. Acute Organ Injury: Evidence That CO[sub(2)] Is Protective......Page 382
V. Mechanisms of CO[sub(2)]-Induced Protection......Page 391
VI. Molecular Mechanisms of Hypercapnia-Induced Tissue Injury......Page 395
VII. Administration and Dose Response......Page 397
VIII. Role of Buffering......Page 398
IX. Hypercapnia—Clinical Studies......Page 400
X. Future Directions......Page 401
References......Page 402
I. Introduction......Page 412
II. Effects of Mechanical Ventilation on Alveolar Epithelial Barrier Function......Page 414
III. Alveolar Epithelial Ion and Fluid Transport......Page 420
IV. Effects of Mechanical Strain on Epithelial Inflammatory Mediators......Page 422
V. Consequences of the Loss of Epithelial Barrier Function......Page 426
VI. Effects of VILI on Surfactants......Page 427
VII. Summary......Page 428
References......Page 429
I. Introduction—VALI and Genome Medicine......Page 438
II. Challenges to Unraveling the Genetics of VALI......Page 439
III. Current Status of VALI/VILI Genetics and the Candidate Gene Approach......Page 441
IV. Gene Expression in Animal Models of VILI......Page 443
V. Ortholog Gene Database in VALI and Mechanical Stress......Page 447
VI. Regional Heterogeneity in Ventilator-Associated Mechanical Stress......Page 448
VII. Pre-B-Cell Colony–Enhancing Factor as an ALI Candidate Gene......Page 453
VIII. Preliminary PBEF Genotyping in ALI Patients......Page 455
IX. Preliminary IL-6 Genotyping in VALI......Page 457
X. Summary......Page 458
References......Page 459
I. Introduction......Page 466
II. Histological Evidence of Mechanical Ventilation–Induced Lung Distortion/Overinflation......Page 467
III. CT Evidence of Mechanical Ventilation–Induced Lung Distortion/Overinflation......Page 471
References......Page 477
I. Introduction......Page 482
II. Anatomic Imaging of VILI: Quantifying Edema Accumulation......Page 483
III. Functional Imaging of VILI......Page 491
IV. Molecular Imaging of VILI......Page 496
References......Page 503
I. Introduction......Page 510
II. MV and the Cytokine Network......Page 511
III. Modulation of the Cytokine Network in ALI: Evidence from Studies......Page 514
IV. Impact of MV on the Cytokine Network in Healthy Lungs......Page 524
References......Page 527
I. Introduction......Page 532
II. Traditional Approach to MV in ALI/ARDS......Page 533
III. Mechanisms of VILI......Page 534
IV. Lung-Protective Ventilation......Page 535
V. Clinical Trials of Lung-Protective MV Strategies......Page 538
VI. Controversies......Page 544
VII. Summary......Page 548
References......Page 549
I. Introduction......Page 554
II. Randomized, Controlled Trials of Tidal Volume Reduction in ARDS......Page 556
III. Meta-Analyses of the RCTs of Tidal Volume Reduction During ARDS......Page 562
IV. Impact of the Low Tidal Volume Trials on Practice Patterns......Page 567
V. Conclusions......Page 568
References......Page 569
I. Introduction......Page 572
II. Experimental Scientific Principles......Page 576
III. Computerized Protocol Experience......Page 610
IV. Summary......Page 624
References......Page 626
I. Introduction......Page 646
II. Understanding Current Practice......Page 648
III. Do We Know Why Clinicians Do Not Follow Practice Guidelines?......Page 650
IV. Barriers to Changing Practice in the ICU......Page 651
V. Models of Changing Clinical Practice......Page 653
VII. Conclusions......Page 656
References......Page 657
I. Introduction—Questions to Be Addressed......Page 662
II. Inclusion and Exclusion Criteria......Page 666
III. Outcomes......Page 667
IV. Study Designs......Page 669
V. The RCT......Page 670
VI. Ethical Issues in a Clinical Trial......Page 673
VII. Understanding the Results of a Clinical Trial......Page 679
VIII. Nonrandomized Cohort Studies......Page 680
IX. Evidence-Based Medicine and Hierarchy of Study Designs......Page 683
References......Page 684
II. Perfluorocarbon Liquids as Media for Breathing......Page 690
III. Effects of Perfluorocarbons on Inflammation and Oxidative Injury......Page 691
IV. In Vitro Effects of Neat Perfluorocarbon Liquids Involving Surface Tension......Page 695
V. Effects of Ventilation with Perfluorocarbons on Lung Injury......Page 696
VI. Mechanical Protection from Lung Injury by Perfluorocarbon Ventilation......Page 700
References......Page 703
I. Introduction—The Pulmonary Surfactant System......Page 712
II. Surfactant Alterations and Replacement Treatment in ALI/ARDS......Page 716
III. Role of the Pulmonary Surfactant System in VILI......Page 719
IV. Conclusions......Page 724
References......Page 725
I. Introduction......Page 732
II. Background......Page 733
III. Rationale for HFOV......Page 734
IV. Clinical Experience with HFOV......Page 739
V. Future Directions in the Application of HFOV......Page 740
References......Page 742
II. Gene Therapy for ALI......Page 746
IV. Conclusions......Page 751
References......Page 752
A......Page 756
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C......Page 758
E......Page 760
F......Page 761
H......Page 762
I......Page 763
L......Page 764
M......Page 765
N......Page 766
P......Page 767
R......Page 769
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Z......Page 773