Arginine reduces leukocyte/endothelial cell interaction in a model of normotensive endotoxemia without attenuating capillary perfusion failure

Introduction

Sepsis and septic multiorgan failure are still associated with a high mortality. Recent pathophysiological studies could show that a substantial depletion of the semi-essential amino acid arginine occurs during sepsis. However, the effects of a high-dosed supplementation of L-arginine on the microcirculation have not been well characterised. This study addresses the effect of an intravenous L-arginine application on the microcirculation in a well-established model of normotensive endotoxemia.

Methods

In a dorsal skinfold chamber preparation in male Syrian golden hamsters, normotensive endotoxemia was induced by intravenous lipopolysaccharide (LPS) administration (Escherichia coli, 2 mg/kg BW). Before and 30 minutes, 3 hours, 8 hours and 24 hours after LPS application, arteriolar and venular leukocyte rolling and adhesion as well as functional capillary density as a parameter of microvascular perfusion injury were quantified by intravital microscopy. In the treatment group, animals received intravenous L-arginine (50 mg/kg BW, n = 5) 15 minutes before LPS administration. Animals infused with the stereo isomer D-arginine (n = 4, 50 mg/kg BW) or sodium chloride (NaCl 0.9%, vehicle) served as controls.

Results

Administration of LPS markedly increased leukocyte rolling and adherence in control animals (P < 0.01 vs baseline). L-Arginine induced a significant reduction of leukocyte rolling (P < 0.05) and adherence (P < 0.01) in postcapillary venules, whereas D-arginine did not lead to significant differences when compared with vehicle controls. Interestingly, despite its effect on leukocyte/endothelial cell interaction, L-arginine did not attenuate capillary perfusion failure.

Conclusion

L-Arginine supplementation results in a significant reduction of LPS-induced leukocyte/endothelial cell interaction in this in-vivo microcirculation model (dorsal skinfold chamber). The lack of improvement in capillary perfusion has to be further characterised in additional studies.