ABSTRACT
OBJECTIVES: Fat embolism syndrome is a clinical issue in subjects with long-bone fracture. It may lead to acute lung injury. The mechanisms and therapeutic regimen remain unclear. The present study was designed to investigate the pathologic and biochemical changes after fat embolization in isolated rat lungs, and to test the effects of posttreatment with N-acetylcysteine (NAC). DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: A total of 36 perfused lungs isolated from Sprague-Dawley rats. INTERVENTIONS: The isolated lungs were randomly assigned to receive physiologic saline solution (vehicle group), fat embolism (FE group), or FE with NAC posttreatment (FE + NAC group). There were 12 isolated lungs in each group. FE was produced by introduction of corn oil micelles. NAC at a dose 150 mg/kg was given 10 mins after FE. MEASUREMENTS AND MAIN RESULTS: The extent of acute lung injury was evaluated by lung weight change, protein concentration in bronchoalveolar lavage, and exhaled nitric oxide. We also measured the pulmonary arterial pressure and capillary filtration coefficient and determined the nitrate/nitrite, methylguanidine, tumor necrosis factor-alpha, and interleukin-1beta in lung perfusate. Histopathologic changes of the lung were examined and quantified. The levels of neutrophil elastase and myeloperoxidase were determined. The expression of inducible nitric oxide synthase was detected. FE caused acute lung injury as evidenced by the lung weight changes, increases in exhaled nitric oxide and protein concentration in bronchoalveolar lavage, pulmonary hypertension, increased capillary filtration coefficient, and lung pathology. The insult also increased nitrate/nitrite, methylguanidine, tumor necrosis factor-alpha, and interleukin-1beta in lung perfusate, increased neutrophil elastase and myeloperoxidase levels, and upregulated inducible nitric oxide synthase expression. Posttreatment with NAC abrogated these changes induced by FE. CONCLUSION: FE caused acute lung injury and associated biochemical changes. Posttreatment with NAC was effective to alleviate the pathologic and biochemical changes caused by FE.
Subject(s)
Acetylcysteine/therapeutic use , Embolism, Fat/drug therapy , Expectorants/therapeutic use , Pulmonary Embolism/drug therapy , Respiratory Distress Syndrome/prevention & control , Animals , Embolism, Fat/complications , Embolism, Fat/enzymology , Leukocyte Elastase/metabolism , Male , Nitric Oxide Synthase Type II/metabolism , Peroxidase/metabolism , Pulmonary Embolism/complications , Pulmonary Embolism/enzymology , Rats , Rats, Sprague-Dawley , Respiratory Distress Syndrome/enzymology , Respiratory Distress Syndrome/etiologyABSTRACT
In a multicenter study (eight centers), we determined secretory phospholipase A(2) (sPLA(2)) levels in patients with sickle cell disease and acute chest syndrome (ACS). The diagnosis of ACS was made according to established criteria. The sPLA2 levels were determined in blood samples collected at baseline (time of diagnosis) and serially thereafter up to day 22-35 follow-up visits. Thirty-four of 43 (80%) patients with ACS had enzyme levels > or =1.00 AU at baseline. The enzyme levels decreased significantly on Days 2 through Days 25-35 after baseline. Nine of 43 (20%) patients had baseline sPLA2 values of <1.00 AU with six of them never exceeding 1.00 AU at any point in time during follow-up. The data indicate that the reliability of sPLA(2( for predicting the development of ACS is not perfect (100%) as was previously reported but occurs in about 80% of the patients.
Subject(s)
Anemia, Sickle Cell/enzymology , Lung Diseases/enzymology , Phospholipases A/blood , Acute Disease , Adolescent , Adult , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/complications , Biomarkers , Child , Child, Preschool , Embolism, Fat/blood , Embolism, Fat/enzymology , Embolism, Fat/etiology , Female , Follow-Up Studies , Group II Phospholipases A2 , Humans , Lung Diseases/blood , Lung Diseases/etiology , Male , Phospholipases A2 , Predictive Value of Tests , Pulmonary Embolism/blood , Pulmonary Embolism/enzymology , Pulmonary Embolism/etiology , SyndromeABSTRACT
Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non-SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100-fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.
Subject(s)
Anemia, Sickle Cell/complications , Anemia, Sickle Cell/enzymology , Lung Diseases/etiology , Phospholipases A/blood , Acute Disease , Adolescent , Adult , Child , Child, Preschool , Embolism, Fat/enzymology , Embolism, Fat/etiology , Fatty Acids, Nonesterified/metabolism , Female , Humans , Infant , Inflammation/enzymology , Ischemia/enzymology , Ischemia/etiology , Lung Diseases/enzymology , Lung Diseases/physiopathology , Male , Phospholipases A2 , Pneumonia/enzymology , Pulmonary Embolism/enzymology , Pulmonary Embolism/etiologyABSTRACT
Artificial fat embolism in rabbits was caused by injection of olive oil and Lipiodol Ultrafluid into the ear vein. Electron-microscopic and histochemical observations of the lung were made. The content of nonspecific esterase was evaluated. Serious defects of blood vessels and pneumocytes as well as an increase in alveolar macrophages and capillary thrombosis were noted. The endothelial cells became considerably larger and necrosis of endothelial cells and capillary destruction even occurred. Fat appeared interstially and in the alveolus. Tissue reaction is much greater in olive oil than in contrast medium. This is due to their different chemical composition. The strong tissue reaction in olive oil is caused by glycerol and unsaturated fatty acids occurring in hydrolysis. Fat emboli are primarily eliminated by enzymatic splitting. Normally alveolar macrophages and endothelial cells contain little nonspecific esterase. After application of fatty fluids they react with an increase in the content of esterase. Alveolar epithelium seems to participate in enzymatic fat splitting.
