Gründling M, Lehmann Ch, Saeger D, Bohnenstengel S, Pavlovic D, Bac V, Usichenko T, Meissner K, Wendt M, Hung O, Murphy M, Whynot S, Lindequist U
Klinik für Anästhesiologie, Ernst-Moritz-Arndt-Universität Greifswald, Germany.
Clin Hemorheol Microcirc. 2008;38(3):163-70.
KKP723 (KKP), a derivative of ampicillin, is a newly developed beta-lactam antibiotic. Using an experimental endotoxemia model, the intestinal microcirculation in four groups of animals were evaluated using intravital microscopy (IVM). The groups included were a control group, an endotoxemic group (15 mg/kg i.v. LPS from E. coli), an ampicillin (50 mg/kg i.v.) treated endotoxemic group and an endotoxemic group treated with KKP (67.4 mg/kg i.v.). Ampicillin treatment resulted in a significant reduced number of firmly adhering leukocytes in intestinal submucosal venules. KKP treatment did not show this effect on leukocyte activation. We found no changes of the functional capillary density (FCD) of the intestinal wall by treatment with ampicillin or its derivative KKP. The increased leukocyte adherence in the KKP treated LPS animals may be explained by a loss of a possible ampicillin-related anti-inflammatory effect by the biotransformation process. The endotoxemia IVM model is useful to detect effects of antibiotics in an impaired microcirculation.
KKP723（KKP）是氨苄西林的衍生物，是一种新开发的β-内酰胺类抗生素。利用实验性内毒素血症模型，通过活体显微镜检查（IVM）评估四组动物的肠道微循环。所包括的组有对照组、内毒素血症组（静脉注射15mg/kg来自大肠杆菌的脂多糖）、氨苄西林（静脉注射50mg/kg）治疗的内毒素血症组和用KKP（静脉注射67.4mg/kg）治疗的内毒素血症组。氨苄西林治疗导致肠黏膜下小静脉中牢固黏附的白细胞数量显著减少。KKP治疗对白细胞活化未显示出这种作用。我们发现用氨苄西林或其衍生物KKP治疗后肠壁的功能性毛细血管密度（FCD）没有变化。在接受KKP治疗的脂多糖动物中白细胞黏附增加可能是由于生物转化过程中可能与氨苄西林相关的抗炎作用丧失所致。内毒素血症IVM模型有助于检测抗生素在受损微循环中的作用。
