Department of Anaesthesiology and Pain Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
Int J Mol Med. 2011 Aug;28(2):187-92. doi: 10.3892/ijmm.2011.690. Epub 2011 May 6.
Post-operative pulmonary complications such as systemic inflammatory response syndrome (SIRS), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are strongly associated with morbidity and mortality after esophagectomy. Post-operative administration of sivelestat sodium hydrate (sivelestat), a selective inhibitor of neutrophil elastase (NE), has been shown to improve the post-operative clinical course after esophagectomy. This study aimed to evaluate the effect of prophylactic administration of sivelestat on bronchial inflammatory responses. We randomized 24 patients into two groups. One group received 0.2 mg/kg/h sivelestat from the induction of anesthesia to post-operative day 1 (sivelestat group) and the other group received the same amount of physiological saline (control group). Bronchial alveolar epithelial lining fluid (ELF) samples were obtained from both groups at the induction of anesthesia and at the end of surgery. The serum and ELF levels of interleukin (IL)-6 and IL-8 were measured by enzyme-linked immunosorbent assay, and NE activity was spectrophotometrically determined using the same samples. Although IL-6 levels in the ELF significantly increased at the end of surgery compared with the pre-operative levels in both groups, the IL-8 levels and NE activity did not significantly increase at the end of the surgery compared to the corresponding pre-operative values in the sivelestat group. Moreover, IL-8 levels and NE activity in the ELF were significantly reduced at the end of surgery in the sivelestat group compared with corresponding values in the control group. The durations of ALI and ARDS were apparently shorter in the sivelestat group and the duration of SIRS was significantly shorter in the sivelestat group compared to the control group. We demonstrated that prophylactic use of sivelestat mitigated bronchial inflammation by suppressing NE activity and IL-8 levels in the ELF and shortened the duration of SIRS after transthoracic esophagectomy.
术后肺部并发症，如全身炎症反应综合征（SIRS）、急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS），与食管癌手术后的发病率和死亡率密切相关。术后给予中性粒细胞弹性蛋白酶（NE）选择性抑制剂西维来司他钠（sivelestat）可改善食管癌手术后的临床病程。本研究旨在评估预防性给予 sivelestat 对支气管炎症反应的影响。我们将 24 例患者随机分为两组。一组患者从麻醉诱导开始至术后第 1 天（sivelestat 组）给予 0.2mg/kg/h sivelestat，另一组患者给予等量生理盐水（对照组）。两组患者均在麻醉诱导时和手术结束时采集支气管肺泡上皮衬液（ELF）样本。通过酶联免疫吸附试验测定血清和 ELF 中白细胞介素（IL）-6 和 IL-8 的水平，并用相同的样本通过分光光度法测定 NE 活性。尽管两组患者 ELF 中的 IL-6 水平在手术结束时与术前水平相比显著升高，但与 sivelestat 组相应的术前值相比，IL-8 水平和 NE 活性在手术结束时并未显著升高。此外，与对照组相比，sivelestat 组患者 ELF 中的 IL-8 水平和 NE 活性在手术结束时明显降低。sivelestat 组的 ALI 和 ARDS 持续时间明显缩短，SIRS 持续时间明显短于对照组。我们的研究结果表明，预防性使用 sivelestat 通过抑制 ELF 中的 NE 活性和 IL-8 水平减轻了支气管炎症，并缩短了经胸食管癌手术后 SIRS 的持续时间。
