Acute lung injury : study of pathogenesis and therapeutic interventions

by Rocksén, David

Abbreviations Introduction…………………………………………………………………. 13 Definitions of ALI and ARDS……………………………………………….15 Incidence…………………………………………………………………….. 16 Risk factors and mortality…………………………………………………... 17 Direct lung injury……………………………………………………... 17 Indirect lung injury……………………………………………………. 17 Lung pathology in ARDS…………………………………………………... 19 Pathogenesis………………………………………………………………… 22 Inflammatory response……………………………………………….. 22 Macrophages………………………………………………... 22 Neutrophils…………………………………………………. 23 Lymphocytes………………………………………………... 24 Cytokines and chemokines………………………………….. 25 Direct injury…………………………………………………………... 26 Pharmacological treatment………………………………………………….27 Corticosteroids………………………………………………………... 27 Antioxidants…………………………………………………………... 27 Other pharmacological efforts………………………………………… 28 Animal models of ALI/ARDS……………………………………………… 29 Exposure to endotoxin………………………………………………... 29 Animal models of endotoxin inhalation……………………... 30 Systemic administration of endotoxin……………………….. 31 Two-hit models………………………………………………………. 31 Shwartzman reaction………………………………………... 32 Other animal models of ALI/ARDS…………………………………. 33 Aims of the thesis…………………………………………………………… 35 Methodological considerations…………………………………………….. 37 Main results and discussion………………………………………………... 43 Generalized Shwartzman reaction as an animal model of acute respiratory distress syndrome…………………………. 43 Lung neutrophilia in acute lung inflammation, septic shock and in the generalized Shwarzman reaction……………… 45 Activation of lymphocytes in endotoxin-induced airway inflammation and in the generalized Shwartzman reaction……………..47 Treatment with dexamethasone in different experimental animal models of ALI/ARDS…………………………... 50 Treatment with antioxidants in different experimental animal models of ALI/ARDS…………………………... 51 Final comments……………………………………………………………... 55