title: Norepinephrine and nomega-monomethyl-L-arginine in porcine septic shock: effects on hepatic O2 exchange and energy balance.
abstract: We compared the effects of norepinephrine (NOR; n = 11) and the nonselective nitric oxide synthase inhibitor Nomega-monomethyl-L-arginine (L-NMMA; n = 11) on hepatic blood flow (Q 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 (Q) achieved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in Q, 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 Q to preshock values. Whereas NOR also increased Q liv and, hence, hepatic O2 delivery (hDO2), but did not affect hepatic O2 uptake (hVO2), L-NMMA influenced neither Q 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.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik für Anästhesiologie, Ulm, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Träger
authors.forename: P
authors.initials: P
authors.lastname: Radermacher
authors.forename: K M
authors.initials: KM
authors.lastname: Rieger
authors.forename: A
authors.initials: A
authors.lastname: Vlatten
authors.forename: J
authors.initials: J
authors.lastname: Vogt
authors.forename: T
authors.initials: T
authors.lastname: Iber
authors.forename: J
authors.initials: J
authors.lastname: Adler
authors.forename: U
authors.initials: U
authors.lastname: Wachter
authors.forename: R
authors.initials: R
authors.lastname: Grover
authors.forename: M
authors.initials: M
authors.lastname: Georgieff
authors.forename: B
authors.initials: B
authors.lastname: Santak
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D004731:Endotoxins; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D005947:Glucose; D009638:Norepinephrine