Effects of coagulation factor XIII on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation in experimental endotoxemia

Abstract

Introduction: The objective of this study was to determine the effects of the administration of the coagulation factor XIII (F XIII) on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia.

Methods: In a prospective, randomized, controlled animal study 42 male Wistar rats were divided into three groups. Group 1 served as the control group. Groups 2 (lipopolysaccharide (LPS) group) and 3 (F XIII group) received endotoxin infusions (2.5 mg/kg/h for 2 hours). In group 3, 50 U/kg body weight F XIII was continuously administered during the first 30 minutes of endotoxemia. F XIII levels were measured in all animals. One half of the animals of each group were studied for intestinal functional capillary density (FCD) and leukocyte adherence on venular endothelium by intravital fluorescence microscopy (IVM). In the other half of each group, mesenteric plasma extravasation (FITC-albumin) was determined by IVM.

Results: The F XIII level was significantly increased in the F XIII treatment group. In the LPS group, endotoxemia led to a significant reduction of mucosal FCD (-18.5%; p < 0.01 versus control group). F XIII administration in the F XIII group attenuated the decrease in mucosal FCD (-3.7% compared to control; p < 0.05 versus LPS group). During endotoxemia, a significant increase of leukocyte adherence at the endothelium could be noted in the LPS group compared to the control group. Leukocyte adherence at the endothelium and plasma extravasation in the F XIII group did not differ significantly from the LPS group.

Conclusion: Factor XIII protected mucosal capillary perfusion against endotoxin-induced impairment in an experimental sepsis model in rats, whereas leukocyte adherence and plasma extravasation remained unchanged.

Figure 1

Factor XIII activity (percentage of baseline values, mean ± standard error of the mean; *p < 0.05 compared to baseline; ^#p < 0.05 compared to lipopolysaccharide (LPS) group). Control, control group; F XIII, factor XIII treated LPS group; LPS, untreated LPS group.

Figure 2

Effects of factor XIII administration on intestinal functional capillary density (FCD) in the mucosal layer during experimental endotoxemia. FCD after one hour of endotoxemia (mean ± standard error of the mean; *p < 0.05 compared to baseline; ^#p < 0.05 compared to lipopolysaccharide (LPS) group). Control, control group, F XIII, factor XIII treated LPS group; LPS, untreated LPS group.

Figure 3

Effects of factor XIII administration on intestinal leukocyte adherence in the submucosal layer during experimental endotoxemia. Adherent (Adh) leukocytes in V1-/V3-venules after two hours of endotoxemia (mean ± standard error of the mean; *p < 0.05 compared to control group; p > 0.05 lipopolysaccharide (LPS) plus F XIII group compared to LPS group). Control, control group; F XIII, factor XIII treated LPS group; LPS, untreated LPS group.

Figure 4

Effects of factor XIII administration on mesenteric plasma extravasation during experimental endotoxemia. Plasma extravasation after one hour of endotoxemia (mean ± SEM). Control, control group; F XIII, factor XIII treated LPS group; FITC, fluorescein isothiocyanate; LPS, untreated LPS group.