Endogenous glucose release in hyperdynamic porcine endotoxin shock: N^G-monomethyl-L-arginine (L-NMMA) versus noradrenaline

Introduction

Inhibition of nitric oxide (NO) synthesis is currently investigated for the treatment of hypotension associated with septic shock. Since both endotoxin (ETX) and NO have been reported to influence gluconeogenesis we compared the effects of standard vasopressor therapy with noradrenaline (NOR) to L-NMMA on endogenous glucose release during long-term ETX induced shock.

Methods

Pigs were studied in a normotensive, hyperdynamic shock model with volume resuscitation (HES 6%) to keep intrathoracic blood volume constant. Animals were randomly assigned to three groups 12 h after start of ETX infusion. ETX group: no drug treatment (n = 8); NOR group: treatment with NOR (n = 11); L-NMMA group: treatment with L-NMMA (n = 11), both titrated to maintain MAP at preshock levels. Hepatic uptake of glucose precursors as well as endogenous glucose formation (stable isotope approach) were measured.

Results

Data are median and interquartile range. *P < 0.05 vs preshock (RM ANOVA on ranks).**P < 0.05 between groups (ANOVA).

Conclusion

Despite their similar effects on liver hemodynamics and O₂ kinetics neither NOR nor L-NMMA influenced the ETX-induced dissociation between liver uptake rates of glucose precursors and total de novo glucose formation rate.

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