Wang Pengfei, Li Yousheng, Li Jieshou
Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
J Invest Surg. 2009 Sep-Oct;22(5):375-82. doi: 10.1080/08941930903214727.
This study was designed to evaluate the role of different intravascular volume replacement regimens of HES 130/0.4 on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis induced by murine model of cecal ligation and puncture (CLP).
The left colonic anastomosis was performed in 40 rats that were divided into five groups (n = 8/group): saline controls (30 ml/kg); CLP plus saline (30 ml/kg); CLP plus HES (7.5, 15, or 30 ml/kg, respectively). Saline or HES was treated before the construction of left colonic anastomosis and on a regular daily basis. Anastomotic bursting pressures were measured in vivo on day 5. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) activity, malondialdehyde (MDA), reduced glutathione (GSH) levels, and nuclear factor-kappa B (NF-kappa B) activation. The plasma levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were also measured.
Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures, and perianastomotic tissue HP contents and GSH levels, along with increases in perianastomotic tissue MPO activity, MDA levels and NF-kappa B activation and plasma levels of TNF-alpha and IL-6. After treated with HES, these provoked perianastomotic tissue MPO activity, MDA levels, NF-kappa B activation, and plasma levels of TNF-alpha and IL-6 were suppressed and GSH levels were restored, especially in 15 ml/kg HES group. Without obvious influence on systemic nutritional condition, HES 15 ml/kg but not HES 7.5 ml/kg significantly increased anastomotic bursting pressures, and perianastomotic tissue HP contents. However, HES 30 ml/kg even led to adverse effects on anastomotic bursting pressures.
This study showed that moderate doses (15 ml/kg) of HES 130/0.4 administration significantly prevented this intraperitoneal sepsis-induced impaired anastomotic healing of the left colon. It also suggested the possibility of poorer anastomotic healing receiving HES at higher doses (30 ml/kg). Clearly, HES 130/0.4 now should not be recommended to use at a high doses postoperatively in sepsis.
本研究旨在评估在盲肠结扎穿孔（CLP）小鼠模型诱导的腹腔内脓毒症情况下，不同剂量的羟乙基淀粉130/0.4（HES 130/0.4）血管内容量替代方案对左半结肠吻合口愈合过程的作用。
对40只大鼠进行左半结肠吻合术，并将其分为五组（每组n = 8）：生理盐水对照组（30 ml/kg）；CLP加生理盐水组（30 ml/kg）；CLP加HES组（分别为7.5、15或30 ml/kg）。在构建左半结肠吻合术前及之后每天进行生理盐水或HES治疗。在第5天测量体内吻合口破裂压力。获取组织样本以分析羟脯氨酸（HP）含量、髓过氧化物酶（MPO）活性、丙二醛（MDA）、还原型谷胱甘肽（GSH）水平以及核因子-κB（NF-κB）激活情况。同时测量血浆肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6水平。
腹腔内脓毒症导致结肠吻合口破裂压力、吻合口周围组织HP含量和GSH水平显著降低，同时吻合口周围组织MPO活性、MDA水平、NF-κB激活以及血浆TNF-α和IL-6水平升高。用HES治疗后，这些引发的吻合口周围组织MPO活性、MDA水平、NF-κB激活以及血浆TNF-α和IL-6水平受到抑制，GSH水平得以恢复，尤其是在15 ml/kg HES组。在对全身营养状况无明显影响的情况下，15 ml/kg的HES显著增加了吻合口破裂压力和吻合口周围组织HP含量，而7.5 ml/kg的HES则未产生此效果。然而，30 ml/kg的HES甚至对吻合口破裂压力产生了不良影响。
本研究表明，中等剂量（15 ml/kg）的HES 130/0.4给药可显著预防这种腹腔内脓毒症诱导的左半结肠吻合口愈合受损。这也提示了高剂量（30 ml/kg）HES可能导致吻合口愈合较差的可能性。显然，目前不建议在脓毒症术后高剂量使用HES 130/0.4。
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