OBJECTIVES: Oleic acid has been used to induce acute lung injury (ALI) in animals. In patients with acute respiratory distress syndrome (ARDS), the blood level of oleic acid was increased. The mechanism and therapeutic regimen of ARDS and oleic acid-induced ALI remain undefined. In the present study, we investigated the oleic acid-induced changes in lung variables for the measure of ALI, inflammatory mediators, and neutrophil-derived substances. We evaluated the effects of pretreatment and posttreatment with propofol. DESIGN: Randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Fifty adult male Sprague-Dawley rats weighing 250-300 g. INTERVENTIONS: We employed a conscious and unrestrained rat model. Oleic acid at a dose of 100 mg/kg was administered intravenously. Propofol (30 mg/kg) was given by intravenous infusion (6 mg/kg/min for 5 mins) 30 mins before (pretreatment) and 30 mins after (posttreatment) oleic acid. MEASUREMENTS AND MAIN RESULTS: We monitored the arterial pressure, heart rate, and blood gas. The lung weight changes, exhaled nitric oxide, protein concentration in bronchoalveolar lavage, and Evans blue content in lung tissue were determined. The plasma nitrate/nitrite, methylguanidine, cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-10), neutrophil elastase, myeloperoxidase, malondialdehyde, and sodium- and potassium-activated adenosine triphosphatase (Na+-K+-ATPase) were detected. Histopathological examination of the lung was performed. Oleic acid caused systemic hypotension and severe ALI as evidenced by the increases in the extent of ALI, impairment of pulmonary functions (blood gas variables), and lung pathology. In addition, oleic acid significantly increased inflammatory mediators and neutrophil-derived factors but depressed Na+-K+-ATPase. The inducible nitric oxide synthase was up-regulated. Pre- or posttreatment with propofol was capable of reversing the oleic acid-induced changes and attenuating the extent of ALI. CONCLUSIONS: Oleic acid resulted in sepsis-like responses including ALI, inflammatory reaction, and increased neutrophil-derived factors. It depressed the Na+-K+-ATPase activity but up-regulated inducible nitric oxide synthase. Treatment with propofol abrogated or reversed the oleic acid-induced changes.
OBJECTIVES:Oleic acid has been used to induce acute lung injury (ALI) in animals. In patients with acute respiratory distress syndrome (ARDS), the blood level of oleic acid was increased. The mechanism and therapeutic regimen of ARDS and oleic acid-induced ALI remain undefined. In the present study, we investigated the oleic acid-induced changes in lung variables for the measure of ALI, inflammatory mediators, and neutrophil-derived substances. We evaluated the effects of pretreatment and posttreatment with propofol. DESIGN: Randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Fifty adult male Sprague-Dawley rats weighing 250-300 g. INTERVENTIONS: We employed a conscious and unrestrained rat model. Oleic acid at a dose of 100 mg/kg was administered intravenously. Propofol (30 mg/kg) was given by intravenous infusion (6 mg/kg/min for 5 mins) 30 mins before (pretreatment) and 30 mins after (posttreatment) oleic acid. MEASUREMENTS AND MAIN RESULTS: We monitored the arterial pressure, heart rate, and blood gas. The lung weight changes, exhaled nitric oxide, protein concentration in bronchoalveolar lavage, and Evans blue content in lung tissue were determined. The plasma nitrate/nitrite, methylguanidine, cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-10), neutrophil elastase, myeloperoxidase, malondialdehyde, and sodium- and potassium-activated adenosine triphosphatase (Na+-K+-ATPase) were detected. Histopathological examination of the lung was performed. Oleic acid caused systemic hypotension and severe ALI as evidenced by the increases in the extent of ALI, impairment of pulmonary functions (blood gas variables), and lung pathology. In addition, oleic acid significantly increased inflammatory mediators and neutrophil-derived factors but depressed Na+-K+-ATPase. The inducible nitric oxide synthase was up-regulated. Pre- or posttreatment with propofol was capable of reversing the oleic acid-induced changes and attenuating the extent of ALI. CONCLUSIONS:Oleic acid resulted in sepsis-like responses including ALI, inflammatory reaction, and increased neutrophil-derived factors. It depressed the Na+-K+-ATPase activity but up-regulated inducible nitric oxide synthase. Treatment with propofol abrogated or reversed the oleic acid-induced changes.
Authors: Ana Paula Cassiano Silveira; Daniella Alves Vento; Agnes Afrodite Sumarelli Albuquerque; Andrea Carla Celotto; Cristiane Tefé-Silva; Simone Gusmão Ramos; Tales Rubens de Nadai; Alfredo José Rodrigues; Omero Benedicto Poli-Neto; Paulo Roberto Barbosa Evora Journal: Ann Transl Med Date: 2016-01
Authors: Ana Fernandez-Bustamante; Jelena Klawitter; John E Repine; Amanda Agazio; Allison J Janocha; Chirag Shah; Marc Moss; Ivor S Douglas; Zung Vu Tran; Serpil C Erzurum; Uwe Christians; Tamas Seres Journal: Anesthesiology Date: 2014-09 Impact factor: 7.892