抑肽酶或氨甲环酸对心脏手术后婴儿蛋白水解/细胞因子谱的影响。
Effects of aprotinin or tranexamic acid on proteolytic/cytokine profiles in infants after cardiac surgery.
机构信息
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
出版信息
Ann Thorac Surg. 2010 Jun;89(6):1843-52; discussion 1852. doi: 10.1016/j.athoracsur.2010.02.069.
BACKGROUND
After cardiopulmonary bypass (CPB), elaboration of cytokines, and subsequent induction of interstitial proteases, such as matrix metalloproteinases (MMPs), can result in a complex postoperative course. The serine protease inhibitor, aprotinin, which has been used in congenital heart surgery putatively for modulating fibrinolysis is now unavailable, necessitating the use of lysine analogues such as tranexamic acid (TXA). The present study tested the hypothesis that distinctly different plasma profiles of signaling molecules and proteases would be differentially affected after the administration of aprotinin or TXA in the context of congenital cardiac surgery and CPB.
METHODS
Thirty-seven patients (age, 4.8 +/- 0.3 months) undergoing corrective surgery for ventricular septal defect and tetralogy of Fallot received either aprotinin (n = 22) or TXA (n = 15). Using a high throughput multiplex suspension immunoassay, plasma was serially quantified for cytokines and MMPs: before aprotinin or TXA (baseline), after separation from CPB, and 4, 12, 24, and 48 hours post-CPB.
RESULTS
Tumor necrosis factor-alpha increased initially after CPB in both the aprotinin and TXA groups, but at 24 and 48 hours post-CPB was approximately 50% lower in the aprotinin group (p < 0.05). The IL-10 levels were threefold higher in the TXA group compared with the aprotinin group immediately post-CBP (p < 0.05). Plasma levels of MMP types associated with inflammation, MMP-8, and MMP-9, were twofold higher in the late post-CPB period in the TXA group when compared with the aprotinin group.
CONCLUSIONS
After ventricular septal defect or tetralogy of Fallot repair in children, cytokine induction occurs, which is temporally related to the emergence of a specific MMP profile. Moreover, these unique findings demonstrated differential effects between the serine protease inhibitor aprotinin and the lysine analogue TXA with respect to cytokine and MMP induction in the early postoperative period. The different cytokine-proteolytic profile between these antifibrinolytics may in turn influence biologic processes in the postoperative period.
背景
体外循环（CPB）后，细胞因子的产生以及随后间质蛋白酶（如基质金属蛋白酶 [MMPs]）的诱导，可能导致复杂的术后过程。丝氨酸蛋白酶抑制剂抑肽酶曾被用于先天性心脏病手术，据称可调节纤溶作用，但现已不可用，需要使用赖氨酸类似物如氨甲环酸（TXA）。本研究测试了以下假设，即在先天性心脏手术和 CPB 背景下，给予抑肽酶或 TXA 后，信号分子和蛋白酶的血浆谱会有明显不同，从而产生不同的影响。
方法
37 名（年龄 4.8 ± 0.3 个月）接受室间隔缺损和法洛四联症矫正手术的患者接受了抑肽酶（n = 22）或 TXA（n = 15）治疗。使用高通量悬浮免疫分析，对患者血浆中的细胞因子和 MMP 进行了连续定量分析：在抑肽酶或 TXA 之前（基线）、从 CPB 分离后、CPB 后 4、12、24 和 48 小时。
结果
CPB 后，两组患者的肿瘤坏死因子-α（TNF-α）均先升高，但 CPB 后 24 和 48 小时，抑肽酶组 TNF-α 降低约 50%（p < 0.05）。CPB 后，TXA 组的白细胞介素 10（IL-10）水平比抑肽酶组高 3 倍（p < 0.05）。CPB 后晚期，TXA 组与抑肽酶组相比，与炎症相关的 MMP 类型 MMP-8 和 MMP-9 的血浆水平升高了两倍。
结论
在儿童行室间隔缺损或法洛四联症修复术后，细胞因子诱导发生，其与特定 MMP 谱的出现具有时间相关性。此外，这些独特的发现表明，在术后早期，丝氨酸蛋白酶抑制剂抑肽酶和赖氨酸类似物 TXA 在细胞因子和 MMP 诱导方面存在差异。这些抗纤溶药物之间不同的细胞因子-蛋白水解谱可能反过来影响术后的生物学过程。
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