Am. J. Respir. Crit. Care Med., Volume 159, Number 6, June 1999, 1758-1765

Norepinephrine and N-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, and BORISLAV ANTAK

Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik für Anästhesiologie, Ulm, Germany; and Department of Hospital Critical Care Clinical Development, Glaxo Wellcome Research and Development, Greenford, United Kingdom

We compared the effects of norepinephrine (NOR; n = 11) and the nonselective nitric oxide synthase inhibitor N-monomethyl-L-arginine (L-NMMA; n = 11) on hepatic blood flow ( _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 () achieved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in , 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 to preshock values. Whereas NOR also increased _liv and, hence, hepatic O₂ delivery (hDO₂), but did not affect hepatic O₂ uptake (hVO₂), L-NMMA influenced neither _liv nor hDO₂ and hVO₂. Mean capillary hemoglobin O₂ saturation (HbSc_O2) on the liver surface as well as HbSc_O2 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.

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