Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations

Chen, Hsing I

In animal experiments and clinical investigations, the risk factors causing ALI/ARDS include head injury, intracranial hypertension, [2] [3] [4] [57] [58] [59] [60] [61] [62] sepsis, [12, 17, 35, 37, 39, 42, 44, [63] [64] [65] [66] and infections. [6] [7] [8] [10] [11] [12] 17, 18, [29] [30] [31] 67] Pulmonary embolic disorders Journal of Geriatric Cardiology | [e-mail]; http://www.jgc301.com such as fat and air embolism are less common causes. [7, 15, 28, 47, [68] [69] [70] Ischemia/reperfusion lung injury may develop as a consequence of several pulmonary disorders such as pulmonary artery thromboendarterectomy, thrombolysis after pulmonary embolism and lung transplantation. [13, [51] [52] [53] [71] [72] [73] [74] Gastric aspiration occurs frequently in surgical patients under anesthesia and other causes such as blunt thoracic trauma, impaired glottis competency, and pregnancy. [73, 75, 76] It is one of the major causes of acute respiratory syndrome (ARDS). [77, 78] Intratracheal instillation of hydrochloric acid (HCI) or gastric particles has been employed as experimental model of acute lung injury (ALI). [16, [79] [80] [81] In addition, amphetamine, phorbal myristate acetate, oleic acid have been employed for the induction of ALI. [82] [83] [84] [85] [86] Phorbol myristate acetate (PMA, 12-O-tetradecanoyl-phorbol-13-acetate), an ester derivative from croton oil has been used to induce ALI. [65, 83, 86, 87] Experiments in vivo and in vitro have demonstrated that PMA is a strong neutrophil activator. [87] [88] [89] [90] Activation and recruitment of neutrophil that lead to release of neutrophil elastase and other mediators may play an initial role in the pathogenesis of ALI. [91, 92] The oleic acid-induced ALI has several clinical implications. First, the blood level of oleic acid was significantly elevated in patients with ARDS. [93, 94] Second, the proportion of oleic acid incorporated into surfactant phospholipids was also increased in patients with ARDS and sepsis. [95, 96] These observations have provided evidence to suggest that serum level of oleic acid as a prediction or prognostic factor for ARDS. [84, 93] Early studies focused on the potential toxic effects of high oxygen fractions on inspired air. [97] Ventilator-induced ALI was attributed to the deleterious effects on capillary stress due to alveolar overdistension. Cyclic opening and closing of atelectatic alveoli during mechanical ventilation might cause lung injury and enhance the injured alveoli. Recent evidence indicated that over distension coupled with repeated collapse and reopening of alveoli initiated an inflammatory cascade of proinflammatory cytokines release. [68, [98] [99] [100] In spite of the risk factors and causes, the pathophysiology of ARDS/ALI has generally considered to be initiated by formation of alveolar edema (even hemorrhage) that is enriched with protein, inflammatory cells or red blood cells. After damage of alveolar-capillary barrier, impairment of gas exchange occurs, with decrease in lung compliance and increases in dispersion of ventilation and perfusion and intrapulmonary shunt. Hypoxia, reduction in arterial oxygen partial pressure to fraction of oxygen in inspired air PaO 2 /FiO 2 , hypercapnia ensued despite ventilation with high oxygen. [1, 2, 67, 68, 101, 102] In addition to the potential toxic effects of NO and free radicals, certain chemokines, cytokines, neutrophil elastase, myeloperoxidase and malondialdehyde have been