Response of the rat intestinal microcirculation to experimental endotoxemia is attenuated by ampicillin but not by its derivative KKP723.

Abstract

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.