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西维来司他钠对新生仔猪体外循环后急性肺损伤的影响

The effect of sivelestat sodium on post-cardiopulmonary bypass acute lung injury in a neonatal piglet model.

作者信息

Ando Makoto, Murai Tatsuya, Takahashi Yukihiro

机构信息

Department of Pediatric Cardiac Surgery, Sakakibara Heart Institute,Fuchu-si, Tokyo, Japan.

出版信息

Interact Cardiovasc Thorac Surg. 2008 Oct;7(5):785-8. doi: 10.1510/icvts.2008.177576. Epub 2008 Jul 2.

Abstract

Cardiopulmonary bypass may cause acute lung injury and can seriously affect postoperative outcome, especially in younger patients. A synthesized neutrophil elastase inhibitor, sivelestat sodium, may be most effective when used during cardiopulmonary bypass. After anesthesia induction, sivelestat (2 mg/kg/h) was given to the SS group (n=7), and 0.9% saline solution to the placebo group (n=7). Piglets were placed on hypothermic cardiopulmonary bypass and subjected to myocardial ischemia (2 h) induced by cold crystalloid cardioplegia. At 24 h after surgery, PaO(2)/FiO(2) ratio and alveolar-arterial oxygen difference were significantly better in the SS group (379.1+/-93.9 mmHg and 250.5+/-89.3 mmHg) than the placebo group (232.4+/-105.3 mmHg, and 378.3+/-90.8 mmHg, P<0.05). Interleukin-8 level in the epithelial lining fluid was above the lowest standard in 6 out of 7 (4.5, 12.9, 24.6, 27.7, 37.7, and 159.8; mean=44.5+/-57.6 g/l) in the placebo group, and in 2 out of 7 (36.1 and 67.8 g/l) in the SS group (P<0.05). The median histological score of acute lung injury in the harvested lung was 3 (2-5) in the placebo group and 1 (1-5) in the SS group (P<0.05). Intraoperative administration of sivelestat effectively reduced neutrophil induction and activation in the lung and improved oxygenation after cardiopulmonary bypass in a piglet model.

摘要

体外循环可能导致急性肺损伤,并严重影响术后结局,尤其是在年轻患者中。一种合成的中性粒细胞弹性蛋白酶抑制剂西维来司他钠,在体外循环期间使用时可能最为有效。麻醉诱导后,SS组(n = 7)给予西维来司他(2 mg/kg/h),安慰剂组(n = 7)给予0.9%生理盐水溶液。将仔猪置于低温体外循环下,并接受冷晶体心脏停搏液诱导的心肌缺血(2小时)。术后24小时,SS组的动脉血氧分压/吸入氧分数值(PaO(2)/FiO(2))和肺泡-动脉氧分压差(379.1±93.9 mmHg和250.5±89.3 mmHg)明显优于安慰剂组(232.4±105.3 mmHg和378.3±90.8 mmHg,P<0.05)。安慰剂组7例中有6例(4.5、12.9、24.6、27.7、37.7和159.8;平均值=44.5±57.6 g/l)上皮衬液中的白细胞介素-8水平高于最低标准,而SS组7例中有2例(36.1和67.8 g/l)(P<0.05)。在收获的肺中,安慰剂组急性肺损伤的组织学评分中位数为3(2 - 5),SS组为1(1 - 5)(P<0.05)。在仔猪模型中,术中给予西维来司他可有效减少肺内中性粒细胞的诱导和激活,并改善体外循环后的氧合。

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