Effects of pentoxifylline on inflammation and lung dysfunction in ventilated septic animals.
Acute respiratory distress syndrome secondary to sepsis is associated with high morbidity and mortality. The purpose of this study was to characterize the effects of ventilatory strategy and the modulating activity of pentoxifylline in a sepsis-induced lung dysfunction model. Male Wistar rats were randomly divided into six groups, undergoing two different ventilatory strategies. Rats received live Escherichia coli or saline intraperitoneally. After 6 hours, the septic animals were treated with either pentoxifylline (25 mg/kg for 20 minutes) or normal saline infusion and ventilated with low tidal volume (6 mL/kg; septic animals with E. coli intraperitoneal [IP] infusion, PTX-treated and ventilated with low tidal volume and septic animals with E. coli IP infusion and ventilated with low tidal volume, respectively) or high tidal volume (12 mL/kg; septic animals with E. coli IP infusion, PTX-treated and ventilated with high tidal volume and septic animals with E. coli IP infusion and ventilated with high tidal volume, respectively) for 3 hours. The control animals received normal saline infusion and, after 6 hours, were ventilated with low or high tidal volume (control animals with saline infusion and ventilated with low tidal volume and control animals with saline infusion and ventilated with high tidal volume, respectively). Lung dysfunctions were assessed by wet-to-dry lung ratios, total cell count, total protein, malondialdehyde, and tumor necrosis factor-alpha concentrations in bronchoalveolar lavage (BAL). Septic animals with E. coli IP infusion and ventilated with high tidal volume presented increased wet-to-dry lung ratios, total cell count, total protein, and malondialdehyde in BAL compared with the septic animals ventilated with low tidal volume. Septic animals treated with pentoxifylline presented higher arterial oxygenation and lower cellular influx, protein leakage, malondialdehyde concentration, and tumor necrosis factor-alpha levels in BAL compared with septic animals undergoing the same ventilatory support strategies (septic animals with E. coli IP infusion and ventilated with low tidal volume and septic animals with E. coli IP infusion and ventilated with high tidal volume). Ventilatory strategy modulated the inflammatory response and pulmonary alterations in a sepsis-induced acute lung injury model, and these effects are improved by pentoxifylline.
Oliveira-Júnior
Itamar Souza
IS
Division of Histology and Structural Biology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Pedro de Toledo, Sao Paulo, Brazil.
Oliveira
Itamar Souza
IS
Oliveira
Wagner Rogério Souza
WR
Cavassani
Samia Santos
SS
Brunialti
Milena Karina Coló
MK
Salomao
Reinaldo
R
D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004927:Escherichia coli Infections / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D008171:Lung Diseases / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D010431:Pentoxifylline / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D012965:Sodium Chloride / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D012965:Sodium Chloride; D008315:Malondialdehyde; D010431:Pentoxifylline