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前列地尔和乌司他丁对先天性心脏病小儿患者体外循环后炎症反应及肺损伤的影响

[Effects of alprostadil and ulinastatin on inflammatory response and lung injury after cardiopulmonary bypass in pediatric patients with congenital heart diseases].

作者信息

Jiang Yi-fei, Wang Wen-wei, Ye Wen-lian, Ni Yu-fei, Li Jun, Chen Xiao-ling, Jin Sheng-wei, Lian Qing-quan

机构信息

Department of Anesthesiology, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2008 Nov 11;88(41):2893-7.

PMID:19080093
Abstract

OBJECTIVE

To investigate the therapeutic effects of alprostadil (Lipo-PGE1) and Ulinastatin on inflammatory response and lung injury after cardiopulmonary bypass (CPB) in pediatric patients with congenital heart diseases.

METHODS

58 children with congenital heart diseases, including atrial septal defect, ventricular septal defect, and atrioventricular septal defect, scheduled to undergo CPB, aged 4 - 72 months, were randomly divided into 4 groups: alprostadil Group P (n = 15) receiving alprostadil 10 ng/ml added into the prime solution and continuous pump infusion of alprostadil 10 ngxkg(-1)xmin(-1) via central vein until the end of operation, Group U (n = 15) receiving ulinastatin 20 000 U/kg divided into several doses to be added into the prime solution, Group PU (n = 14) receiving alprostadil and ulinastatin according to the above protocols, and Group C (control group, n = 14) receiving normal saline of the equal volume. Electrocardiogram (ECG), heart rate (HR), pulse oxygen saturation (SpO(2)), and mean arterial pressure (MAP) were continuously monitored during operation. Duration of mechanical ventilation and staying in ICU were also recorded. Plasma neutrophil (PMN), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP-9) levels in the radial arterial blood samples were measured after induction of anesthesia before CPB (T(1)), 30 minutes and (T(2)), 2 hours (T(3)), 6 hours (T(4)), and 24 hours (T(5)) after the declamping of aorta. Inhaled oxygen concentration and arterial blood gas analysis were recorded at T(1), T(2), and T(3) for calculation of oxygenation index (OI).

RESULTS

There were no significant differences in the MAP and HR among these four groups at any time points (all P > 0.05). The umbers of PMN and the levels of IL-6, IL-8, and TNF-alpha at T(2) and T(3) of Groups P, U, and PU were all significantly lower than that of Group C (all P < 0.05), with those of Group PU being the lowest. The IL-10 levels at T(2) and T(3) of Groups U and PU were significantly higher than that of Group C (both P < 0.05), the level of MMP-9 at T(2) and T(3) of Groups U and PU were significantly lower than that of Group C (all P < 0.05), however, there was not significant difference between Group P and Group C (P > 0.05). The OIs at T(2) of Groups P, U, and PU were significantly higher than that of Group C (all P < 0.05). The mechanical ventilation time of Groups P, U, and PU were all significantly shorter than that of Group C, and that of Group PU was significantly shorter than that of group C (P < 0.05).

CONCLUSION

Decreasing the inflammatory response after CPB, alprostadil and ulinastatin used during CPB effectively reduce the pulmonary injury via inhibition of the neutrophil activation and cytokines release.

摘要

目的

探讨前列地尔(脂微球载体前列腺素E1)和乌司他丁对先天性心脏病小儿患者体外循环(CPB)后炎症反应及肺损伤的治疗作用。

方法

58例先天性心脏病患儿,包括房间隔缺损、室间隔缺损和房室间隔缺损,计划行CPB,年龄4 - 72个月,随机分为4组:前列地尔组(P组,n = 15),将10 ng/ml前列地尔加入预充液中,并经中心静脉持续泵入前列地尔10 ng·kg⁻¹·min⁻¹直至手术结束;乌司他丁组(U组,n = 15),将20 000 U/kg乌司他丁分多次加入预充液中;前列地尔联合乌司他丁组(PU组,n = 14),按上述方案给予前列地尔和乌司他丁;对照组(C组,n = 14),给予等体积生理盐水。术中持续监测心电图(ECG)、心率(HR)、脉搏血氧饱和度(SpO₂)和平均动脉压(MAP)。记录机械通气时间和入住重症监护病房(ICU)的时间。于麻醉诱导后CPB前(T₁)、主动脉开放后30分钟(T₂)、2小时(T₃)、6小时(T₄)和24小时(T₅)采集桡动脉血样本,测定血浆中性粒细胞(PMN)、白细胞介素(IL)-6、IL-8、IL-10、肿瘤坏死因子(TNF)-α和基质金属蛋白酶(MMP)-9水平。于T₁、T₂和T₃记录吸入氧浓度和动脉血气分析结果,计算氧合指数(OI)。

结果

4组在任何时间点的MAP和HR均无显著差异(均P > 0.05)。P组、U组和PU组在T₂和T₃时的PMN数量以及IL-6、IL-8和TNF-α水平均显著低于C组(均P < 0.05),其中PU组最低。U组和PU组在T₂和T₃时的IL-10水平显著高于C组(均P < 0.05),U组和PU组在T₂和T₃时的MMP-9水平显著低于C组(均P < 0.05),然而,P组与C组之间无显著差异(P > 0.05)。P组、U组和PU组在T₂时的OI均显著高于C组(均P < 0.05)。P组、U组和PU组的机械通气时间均显著短于C组,且PU组显著短于C组(P < 0.05)。

结论

CPB期间使用前列地尔和乌司他丁可减轻CPB后的炎症反应,通过抑制中性粒细胞活化和细胞因子释放有效减轻肺损伤。

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Urinary trypsin inhibitor attenuated inflammatory response of patients undergoing cardiopulmonary bypass by inducing activated Treg cells.
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