Norepinephrine and N(ω)-monomethyl-L-arginine in porcine septic shock: Effects on hepatic O2 exchange and energy balance

Karl Träger, Peter Radermacher, Karen M. Rieger, Arnim Vlatten, Josef Vogt, Thomas Iber, Jens Adler, Ulrich Wachter, Robert Grover, Michael Georgieff, Borislav Šantak

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Abstract

We compared the effects of norepinephrine (NOR; n = 11) and the nonselective nitric oxide synthase inhibitor N(ω)-monomethyl-L-arginine (L- NMMA; n = 11) on hepatic blood flow (Q̇(liv)), O2 exchange, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxic shock. Endotoxin (ETX; n = 8) caused a continuous fall in mean arterial pressure (MAP) despite a sustained 50% increase in cardiac output (Q̇) achieved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in Q̇, while the comparable hemodynamic stabilization during L-NMMA infusion resulted from systemic vasoconstriction, increasing the systemic vascular resistance (SVR) about 30% from shock level after 6 h of treatment concomitant with a reduction in Q̇ to preshock values. Whereas NOR also increased Q̇(liv) and, hence, hepatic O2 delivery (hDO2), but did not affect hepatic O2 uptake (hVO2), L-NMMA influenced neither Q̇(liv) nor hDO2 and hVO2. Mean capillary hemoglobin O2 saturation (HbSCO2) on the liver surface as well as HbSCO2 frequency distributions, which mirror microcirculatory O2 availability, remained unchanged as well. Neither treatment influenced the ETX-induced derangements of cellular energy metabolism reflected by the progressive decrease in hepatic lactate uptake rate and increased hepatic venous lactate/pyruvate ratios. ETX nearly doubled the endogenous glucose production (EGP) rate, which was further increased with NOR, whereas L-NMMA nearly restored EGP to preshock levels. Nevertheless, despite the different mechanisms in maintaining blood pressure neither treatment influenced ETX-induced liver dysfunction.

Original languageEnglish (US)
Pages (from-to)1758-1765
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume159
Issue number6
DOIs
StatePublished - Jan 1 1999

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Träger, K., Radermacher, P., Rieger, K. M., Vlatten, A., Vogt, J., Iber, T., Adler, J., Wachter, U., Grover, R., Georgieff, M., & Šantak, B. (1999). Norepinephrine and N(ω)-monomethyl-L-arginine in porcine septic shock: Effects on hepatic O2 exchange and energy balance. American journal of respiratory and critical care medicine, 159(6), 1758-1765. https://doi.org/10.1164/ajrccm.159.6.9808040