Activated protein C improves intestinal microcirculation in experimental endotoxemia in the rat

Objective

We studied the effects of activated protein C (APC) on the intestinal microcirculation during experimental endotoxemia in rats using intravital microscopy.

Design

A prospective, randomized, controlled animal study.

Setting

Experimental laboratory of a university.

Animals

Forty-four male Lewis rats.

Interventions

The animals were divided into four groups. Group 1 served as control. Group 2 (lipopolysaccharide Escherichia coli [LPS]) and group 3 (LPS + APC) received endotoxin infusion (15 mg/kg). In groups 3 and 4 (APC) 2 mg/kg Drotrecogin alfa (activated) was administered. All animals underwent studies of intestinal functional capillary density (FCD) and leukocyte adherence on venular endothelium in the microcirculation of the terminal ileum by intravital fluorescence microscopy (IVM).

Measurements and results

APC reduced significantly the number of firmly adhering leukocytes in V3 venules (416.5 ± 54.7) and V1 venules (235.4 ± 59.8) (Fig. 1) as compared with LPS (678.9 ± 144.4 in V3 venules; 374.5 ± 90.4 in V1 venules; Fig. 2). The FCD (cm/cm²) in the mucosa of LPS rats receiving APC was increased (172.2 ± 14.1) as compared with the LPS rats (143.1 ± 9.6, P < 0.05). The FCD of longitudinal and circular muscular layers showed a better perfusion in rats treated with APC (172.2 ± 14.1 vs 167.4 ± 16.7) in comparison with untreated animals (143.1 ± 9.6 vs 141.1 ± 15.2, P < 0.05).

Figure 1

(abstract P77)

Figure 2

(abstract P77)

Conclusion

APC administration in endotoxemic animals improved microcirculatory perfusion. Moreover, APC treatment revealed anti-inflammatory effects by reducing leukocyte adherence to the endothelium.