Fujii Masahiro, Miyagi Yasuo, Bessho Ryuzo, Nitta Takashi, Ochi Masami, Shimizu Kazuo
Division of Cardiovascular Surgery, Department of Surgery, Nippon Medical School, Tokyo 113-8603, Japan.
Interact Cardiovasc Thorac Surg. 2010 Jun;10(6):859-62. doi: 10.1510/icvts.2009.225243. Epub 2010 Mar 30.
Cardiopulmonary bypass (CPB) has been implicated as a cause of acute lung injury (ALI) in cardiac surgical patients. We used a bronchoscopic microsampling (BMS) probe to examine alveolar biochemical constituents and evaluated the effect of sivelestat sodium hydrate, a novel synthesized polymorphonuclear (PMN) neutrophil elastase inhibitor, on ALI induced by CPB. Twelve patients undergoing aortic valve replacement were treated with either sivelestat 0.2 mg/kg/h (sivelestat group, n=6) or 0.9% saline (control group, n=6) from the start of surgery. Samples were collected by the BMS probe at three time points: after tracheal intubation, 1 h after CPB introduction, and 3 h after CPB termination. Pulmonary function was assessed perioperatively. There were no differences in baseline characteristics. The concentration of PMN elastase was significantly suppressed in the sivelestat group, compared with the control group (P=0.001). The sivelestat group also had lower levels of interleukin-6 and interleukin-8. Alveolar-arterial oxygen difference markedly increased, and a worsening of the PaO(2)/FiO(2) ratio indicated severe impairment after CPB. However, sivelestat attenuated the pattern of physiological deterioration of gas exchange. Sivelestat may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing CPB.
体外循环（CPB）被认为是心脏手术患者急性肺损伤（ALI）的一个原因。我们使用支气管镜微量采样（BMS）探头检测肺泡生化成分，并评估新型合成多形核（PMN）中性粒细胞弹性蛋白酶抑制剂水合西维来司他对CPB诱导的ALI的影响。12例行主动脉瓣置换术的患者从手术开始时分别接受0.2 mg/kg/h水合西维来司他治疗（水合西维来司他组，n = 6）或0.9%生理盐水治疗（对照组，n = 6）。在三个时间点通过BMS探头采集样本：气管插管后、CPB开始后1小时和CPB结束后3小时。围手术期评估肺功能。基线特征无差异。与对照组相比，水合西维来司他组PMN弹性蛋白酶浓度显著降低（P = 0.001）。水合西维来司他组白细胞介素-6和白细胞介素-8水平也较低。肺泡-动脉氧分压差明显增加，CPB后PaO₂/FiO₂比值恶化表明严重受损。然而，水合西维来司他减轻了气体交换生理恶化的模式。水合西维来司他可能减轻中性粒细胞弹性蛋白酶或促炎细胞因子，并改善接受CPB患者的肺功能障碍。
