Effects of dopexamine on the intestinal microvascular blood flow and leucocyte activation in a sepsis model in rats

Abstract

Introduction: Dopexamine may be a therapeutic option to improve hepatosplanchnic perfusion in sepsis. To investigate this possibility, we administered dopexamine in an experimental sepsis model in rats. Methods: This prospective, randomized, controlled laboratory study was conducted in 42 Wistar rats. The animals were divided into three groups. Group 1 served as the control group (CON group). The animals in both groups 2 (LPS group) and 3 (DPX group) received an endotoxin (lipopolysaccharide from Escherichia coli - LPS) infusion (20 mg/kg for 15 minutes). DPX group additionally received dopexamine (0.5 μg/kg per minute over four hours). One half of the animals in each group underwent studies of intestinal microvascular blood flow (IMBF) using laser Doppler fluxmetry. In the other half an intravital microscopic evaluation of leucocyte-endothelial cell interaction in intestinal microcirculation was conducted. Functional capillary density (FCD) in the intestinal mucosa and in the circular as well as longitudinal muscle layer was estimated. Results: One hour after endotoxin challenge, IMBF decreased significantly in LPS group to 51% compared with baseline (P < 0.05). In DPX group (endotoxin plus dopexamine) we found IMBF values significantly higher than those in LPS group (approximately at the level of controls). The impaired FCD following endotoxin challenge was improved by dopexamine in the longitudinal muscle layer (+33% in DPX group versus LPS group; P < 0.05) and in the circular muscle layer (+48% in DPX group versus LPS group; P < 0.05). In DPX group, dopexamine administration reduced the number of firmly adherent leucocytes (-31% versus LPS group; P < 0.05). Plasma levels of tumour necrosis factor-α were reduced by dopexamine infusion (LPS group: 3637 ± 553 pg/ml; DPX group: 1933 ± 201 pg/ml) one hour after endotoxin challenge. Conclusion: Dopexamine administration improved IMBF and FCD (markers of intestinal microcirculation) and reduced leucocyte activation (a marker of inflammation) in experimental sepsis. © 2006 Birnbaum et al.; licensee BioMed Central Ltd.