Vancomycin and to lesser extent tobramycin have vasomodulatory effects in experimental endotoxemia in the rat

Abstract

Antibiotic treatment represents a key component of therapy for severe sepsis. Apart from their antimicrobial efficacy, when choosing antibiotics in septic conditions, vasomodulatory effects should also be taken into account. Aim of this study was to evaluate the vasomodulatory effects of vancomycin (VANCO) and tobramycin (TOBRA) in experimental endotoxemia by using intravital microscopy (IVM) of the intestinal microcirculation and measurements of the arterial contractility in vitro. Endotoxemia was induced in rats by intravenous administration of lipopolysaccharide (LPS). VANCO or TOBRA were given immediately after LPS administration. Intestinal functional capillary density (FCD) and leukocyte-endothelial interactions were evaluated by IVM 2 hrs after LPS challenge. The effects of the antibiotics on the motility of aortal rings were examined in vitro. Leukocyte adhesion was significantly potentiated in the LPS group and in both antibiotic groups as compared to control group. Roller flow in V1 and V3 venules increased in antibiotic treated groups as compared to untreated LPS animals. FCD in the longitudinal muscular and mucosal layers decreased significantly in either endotoxemia or antibiotics treated rats. However, administration of VANCO ameliorated FCD in endotoxemic rats. Both antibiotics, in higher concentration, produced moderate relaxation of the arterial smooth muscle. Tobramycin and vancomycin did not affect the interaction between leukocytes and microvascular endothelium while vancomycin increased functional capillary density in the intestinal wall. Both antibiotics had direct relaxing effects on the vascular smooth muscle. Therefore, vancomycin and to lesser extent tobramycin may influence vascular tone and thereby affect microcirculation in endotoxemia and sepsis.