Blumenthal Stephan, Borgeat Alain, Pasch Thomas, Reyes Livia, Booy Christa, Lambert Maud, Schimmer Ralph C, Beck-Schimmer Beatrice
Department of Anesthesiology, Orthopedic University Clinic Zurich Balgrist, Switzerland.
Anesthesiology. 2006 May;104(5):961-9. doi: 10.1097/00000542-200605000-00012.
Endotoxin causes acute lung injury, which can lead to acute respiratory distress syndrome. Because local anesthetics are known to attenuate inflammatory reactions, ropivacaine was tested for its possible antiinflammatory effect in lipopolysaccharide-induced lung injury in rat alveolar epithelial cells (AECs) and rat pulmonary artery endothelial cells (RPAECs) in vitro and in vivo.
AECs and RPAECs were stimulated for 4 h with lipopolysaccharide or lipopolysaccharide and 1 mum ropivacaine. Messenger RNA (mRNA) for intercellular adhesion molecule 1 was assessed. Isolated neutrophils were incubated with stimulated target cells to quantify adhesion and neutrophil-induced cytotoxicity in AECs and RPAECs. In vivo, lipopolysaccharide was instilled intratracheally with or without 1 mm intratracheally or intravenously administered ropivacaine. Bronchoalveolar lavage was performed 5 h later to determine neutrophil and albumin content, as well as concentrations of inflammatory mediators.
In AECs and RPAECs, ropivacaine attenuated lipopolysaccharide-induced up-regulation of mRNA for intercellular adhesion molecule 1 by 41% and 24%, respectively (P < 0.05). In the presence of ropivacaine, increased neutrophil adhesion was down-regulated by 58% and 44% (P < 0.005), whereas cytotoxicity in AECs and RPAECs was diminished by 28% and 33%, respectively (P < 0.05). Enhanced neutrophil count in lipopolysaccharide lungs was reduced by 56% in the presence of intratracheally instilled ropivacaine (81% with intravenous ropivacaine; P < 0.005). Albumin was decreased by 46% with intratracheal ropivacaine (38% with intravenous ropivacaine; P < 0.05), and inflammatory mediators were decreased by 48-59% (69-81% with intravenous ropivacaine; P < 0.01).
Ropivacaine intervention substantially attenuated the inflammatory response in acute lung injury and thus may carry an interesting potential for antiinflammatory treatment.
内毒素可导致急性肺损伤，进而引发急性呼吸窘迫综合征。由于已知局部麻醉药可减轻炎症反应，因此在体外和体内对大鼠肺泡上皮细胞（AECs）和大鼠肺动脉内皮细胞（RPAECs）中罗哌卡因在脂多糖诱导的肺损伤中的可能抗炎作用进行了测试。
用脂多糖或脂多糖与1μmol罗哌卡因刺激AECs和RPAECs 4小时。评估细胞间黏附分子1的信使核糖核酸（mRNA）。将分离的中性粒细胞与受刺激的靶细胞一起孵育，以量化AECs和RPAECs中的黏附及中性粒细胞诱导的细胞毒性。在体内，气管内滴注脂多糖，同时气管内或静脉内给予或不给予1mmol罗哌卡因。5小时后进行支气管肺泡灌洗，以测定中性粒细胞和白蛋白含量以及炎症介质浓度。
在AECs和RPAECs中，罗哌卡因分别使脂多糖诱导的细胞间黏附分子1的mRNA上调减弱了41%和24%（P<0.05）。在罗哌卡因存在的情况下，中性粒细胞黏附增加分别下调了58%和44%（P<0.005），而AECs和RPAECs中的细胞毒性分别降低了28%和33%（P<0.05）。气管内滴注罗哌卡因时，脂多糖诱导的肺中中性粒细胞计数增加减少了56%（静脉注射罗哌卡因时减少81%；P<0.005）。气管内给予罗哌卡因时白蛋白减少了46%（静脉注射罗哌卡因时减少38%；P<0.05），炎症介质减少了48%-59%（静脉注射罗哌卡因时减少69%-81%；P<0.01）。
罗哌卡因干预可显著减轻急性肺损伤中的炎症反应，因此可能具有抗炎治疗的潜在价值。
