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羟乙基淀粉130/0.4和液体明胶在接受冠状动脉手术患者中的免疫和炎症作用

Immune and inflammatory role of hydroxyethyl starch 130/0.4 and fluid gelatin in patients undergoing coronary surgery.

作者信息

Öztürk Tülün, Onur Ece, Cerrahoğlu Mustafa, Çalgan Mehmet, Nizamoglu Funda, Çivi Melek

机构信息

Department of Anaesthesiology and Reanimation, Celal Bayar University, Faculty of Medicine, Manisa 45020, Turkey.

Department of Biochemistry, Celal Bayar University, Faculty of Medicine, Manisa 45020, Turkey.

出版信息

Cytokine. 2015 Jul;74(1):69-75. doi: 10.1016/j.cyto.2014.10.002. Epub 2014 Nov 4.

DOI:10.1016/j.cyto.2014.10.002
PMID:25458745
Abstract

OBJECTIVES

Compare the effects on inflammatory (TNF-α, IL-6, IL-8 and IL-10) and immunologic (CD3(+), CD4(+), CD8(+), CD11b(+), CD16(+)/56(+) T cells and total lymphocyte concentration) variables of hydroxyethyl starch 130/0.4, 4% modified fluid gelatin, or crystalloid when used as volume replacement fluids for acute normovolemic hemodilution (a blood conservation technique) in coronary artery bypass graft patients.

METHODS

Thirty patients undergoing coronary artery bypass graft surgery were randomized to receive Isolyte S® (Group ISO), 6% hydroxyethyl starch 130/0.4 (Group HES) or 4% modified gelatin solution (Group GEL) for acute normovolemic hemodilution. Blood samples were taken immediately after induction of anaesthesia (T0), and 2 h (T1), 12 h (T2), 24 h (T3), and 48 h (T4) after separation from cardiopulmonary bypass. TNF-α, IL-6, IL-8 and IL-10 levels were determined with commercially available ELISA kits. CD3(+) (mature T cells), CD4(+) (T helper cells), CD8(+) (suppressor cytotoxic T cells), CD16(+)/56(+) (natural killer lymphocytes), and CD11b(+) (Mac-1, adhesion receptor) levels were measured using flow-cytometry reagents. The CD4(+):CD8(+) ratio was calculated.

RESULTS

Between-group comparisons showed significantly higher levels of TNF-α at T1 (2 h after weaning from cardiopulmonary bypass) in Group HES compared to Group ISO (p=0.003). IL-8 was significantly lower in Group HES than Group GEL at T1 (p=0.0005). IL-10 was significantly higher in Group HES than in Group GEL at T1 (p=0.0001). The CD4(+):CD8(+) ratio in Group ISO was significantly lower than that in Group HES at T2 (p=0.003). CD11b(+) levels in Group HES were also higher than those in Group GEL and group ISO at T2, but not significantly. CD16/56(+) levels in Group HES were higher than those in Group GEL at T2 (p<0.003). No excessive hemorrhage occurred in any patient. Mediastinal drainage during the first 24 h after surgery in Group HES (347±207 mL) was not significantly different from that of Group GEL (272±177 mL) or Group ISO (247±109) (p>0.05).

CONCLUSION

Hydroxyethyl starch 130/0.4 reduced pro-inflammatory responses and increased anti-inflammatory responses to a greater degree than gelatin solution and isolyte S®. The use of hydroxyethyl starch, compared to gelatin solution and isolyte S®, resulted in less decrease in the CD4(+):CD8(+) ratio, suggesting less immunosuppression.

摘要

目的

比较羟乙基淀粉130/0.4、4%改良液体明胶或晶体液作为容量替代液用于冠状动脉搭桥手术患者急性等容血液稀释(一种血液保护技术)时,对炎症(肿瘤坏死因子-α、白细胞介素-6、白细胞介素-8和白细胞介素-10)和免疫(CD3(+)、CD4(+)、CD8(+)、CD11b(+)、CD16(+)/56(+) T细胞及总淋巴细胞浓度)变量的影响。

方法

30例行冠状动脉搭桥手术的患者被随机分为三组,分别接受爱索洛(Isolyte S®)(ISO组)、6%羟乙基淀粉130/0.4(HES组)或4%改良明胶溶液(GEL组)进行急性等容血液稀释。在麻醉诱导后即刻(T0)、脱离体外循环后2小时(T1)、12小时(T2)、24小时(T – 3)和48小时(T4)采集血样。使用市售酶联免疫吸附测定(ELISA)试剂盒测定肿瘤坏死因子-α、白细胞介素-6、白细胞介素-8和白细胞介素-10水平。使用流式细胞术试剂测量CD3(+)(成熟T细胞)、CD4(+)(辅助性T细胞)、CD8(+)(抑制性细胞毒性T细胞)、CD16(+)/56(+)(自然杀伤淋巴细胞)和CD11b(+)(Mac-1,黏附受体)水平。计算CD4(+):CD8(+)比值。

结果

组间比较显示,与ISO组相比,HES组在T1(脱离体外循环后2小时)时肿瘤坏死因子-α水平显著更高(p = 0.003)。在T1时,HES组白细胞介素-8水平显著低于GEL组(p = 0.0005)。在T1时,HES组白细胞介素-10水平显著高于GEL组(p = 0.0001)。在T2时,ISO组的CD4(+):CD8(+)比值显著低于HES组(p = 0.003)。在T2时,HES组的CD11b(+)水平也高于GEL组和ISO组,但差异不显著。在T2时,HES组的CD16/56(+)水平高于GEL组(p < 0.003)。所有患者均未发生大出血。HES组术后24小时纵隔引流量(347±207 mL)与GEL组(272±177 mL)或ISO组(247±109 mL)相比,差异无统计学意义(p > 0.05)。

结论

与明胶溶液和爱索洛相比,羟乙基淀粉130/0.4能更大程度地降低促炎反应并增强抗炎反应。与明胶溶液和爱索洛相比,使用羟乙基淀粉导致CD4(+):CD8(+)比值降低幅度较小,提示免疫抑制作用较小。

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