Oliveira-Júnior Itamar Souza, Oliveira Wagner Rogério Souza, Cavassani Samia Santos, Brunialti Milena Karina Coló, Salomao Reinaldo
Division of Histology and Structural Biology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Pedro de Toledo, Sao Paulo, Brazil.
J Trauma. 2010 Apr;68(4):822-6. doi: 10.1097/TA.0b013e3181a5f4b5.
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.
脓毒症继发的急性呼吸窘迫综合征与高发病率和高死亡率相关。本研究的目的是在脓毒症诱导的肺功能障碍模型中，描述通气策略的影响以及己酮可可碱的调节活性。雄性Wistar大鼠被随机分为六组，采用两种不同的通气策略。大鼠腹腔内注射活的大肠杆菌或生理盐水。6小时后，脓毒症动物用己酮可可碱（25mg/kg，持续20分钟）或生理盐水输注进行治疗，并分别采用低潮气量（6mL/kg；腹腔内注射大肠杆菌的脓毒症动物、经己酮可可碱治疗并采用低潮气量通气的脓毒症动物以及腹腔内注射大肠杆菌并采用低潮气量通气的脓毒症动物）或高潮气量（12mL/kg；腹腔内注射大肠杆菌的脓毒症动物、经己酮可可碱治疗并采用高潮气量通气的脓毒症动物以及腹腔内注射大肠杆菌并采用高潮气量通气的脓毒症动物）通气3小时。对照动物接受生理盐水输注，6小时后，分别采用低潮气量或高潮气量通气（分别为接受生理盐水输注并采用低潮气量通气的对照动物以及接受生理盐水输注并采用高潮气量通气的对照动物）。通过支气管肺泡灌洗（BAL）中的肺湿干比、总细胞计数、总蛋白、丙二醛和肿瘤坏死因子-α浓度评估肺功能障碍。与采用低潮气量通气的脓毒症动物相比，腹腔内注射大肠杆菌并采用高潮气量通气的脓毒症动物的肺湿干比、总细胞计数、总蛋白和BAL中的丙二醛增加。与采用相同通气支持策略的脓毒症动物（腹腔内注射大肠杆菌并采用低潮气量通气的脓毒症动物以及腹腔内注射大肠杆菌并采用高潮气量通气的脓毒症动物）相比，用己酮可可碱治疗的脓毒症动物的动脉氧合更高，BAL中的细胞内流、蛋白渗漏、丙二醛浓度和肿瘤坏死因子-α水平更低。通气策略在脓毒症诱导的急性肺损伤模型中调节炎症反应和肺部改变，己酮可可碱可改善这些效应。
