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Expired [sup.13]C[O.sub.2] recovery from an oral L-[1-[sup.13]C] phenylalanine ([[sup.13]C]Phe) dose has been used to quantify liver function. This parameter, however, does not depend solely on liver function but also on total C[O.sub.2] production, Phe turnover, and initial tracer distribution. Therefore, we evaluated the impact of these factors on breath test values. Nine ethyl-toxic cirrhotic patients and nine control subjects received intravenously 2 mg/kg of [[sup.13]C]Phe, and breath and blood samples were collected over 4 h. C[O.sub.2] production was measured by indirect calorimetry. The exhaled [sup.13]C[O.sub.2] enrichments were analyzed by isotope ratio mass spectrometry and the [13C]Phe and L-[1-13C]tyrosine enrichments by gas chromatography-mass spectrometry. The cumulative [sup.13]C[O.sub.2] recovery was significantly lower in cirrhotic patients (7 vs. 12%; P < 0.01), in part due to lower total C[O.sub.2] production rates. Phe turnover in cirrhotic patients was significantly lower (33 vs. 44 [micro]mol*[kg.sup.-1]*[h.sup.-1]; P < 0.05). When these extrahepatic factors were considered in the calculation of the Phe oxidation rate, the intergroup differences were even more pronounced (3 vs. 7 [micro]mol*[kg.sup.-1]*[h.sup.-1]) than those for [sup.13]C[O.sub.2] recovery data. Also, the Phe-to-Tyr conversion rate, another indicator of Phe oxidation, was significantly reduced (0.7 vs. 3.0 [micro]mol*[kg.sup.-1]*[h.sup.-1]). cirrhosis; stable isotopes; [sup.13]C[O.sub.2] recovery; phenylalanine breath test

Objective: To evaluate the effects of the stable prostacyclin analogue iloprost on hepato-splanchnic blood flow, oxygen exchange and metabolism in patients with septic shock. Design: Prospective clinical study. Setting: Intensive care unit in a university clinic. Patients: Eleven patients with septic shock requiring norepinephrine to maintain mean arterial pressure above 70 mmHg. Interventions: Iloprost was incrementally infused to increase cardiac index by 15%. Measurements and main results: Splanchnic blood flow (Qspl) was measured using the steady-state indocyanine-green infusion technique and endogenous glucose production rate (EGP) using a stable isotope approach. Systemic and splanchnic oxygen consumption (VO2), the hepato-splanchnic uptake rates of the glucose precursors lactate, pyruvate, alanine and glutamine, the hepatic venous redox state and gastric mucosal-arterial PCO2 gradients were determined. After a baseline measurement, iloprost infusion was started. After 90 min all measurements were repeated and a third measurement was obtained after another 90 min following iloprost withdrawal. Qspl (baseline I: 0.82/0.75–1.08 l·min·m2; iloprost: 0.94/0.88–1.29 l·min·m2; baseline II: 0.87/0.74–1.09 l·min·m2) and splanchnic oxygen delivery (baseline I: 122/103–166 ml·min·m2; iloprost: 134/117–203 ml·min·m2; baseline II: 130/98–158 ml·min·m2) significantly increased. While systemic VO2 significantly increased (baseline I: 139/131–142 ml·min·m2; iloprost: 147/136–164 ml·min·m2; baseline II: 143/133–154 ml·min·m2) splanchnic VO2 increased in 9 of 11 patients which, however, did not reach statistical significance. EGP significantly decreased (baseline I: 23/16–26 µmol·kg·min; iloprost: 16/14–21 µmol·kg·min; baseline II: 18/12–20 µmol·kg·min), whereas all other parameters of energy metabolism remained unchanged. Conclusion: In patients with septic shock an iloprost-induced increase in cardiac index increased splanchnic blood flow and shifted oxygen utilization from the energy requiring de novo glucose production rate to other oxygen-demanding metabolic pathways. [ABSTRACT FROM AUTHOR]

Objective: We compared the effects of thromboxane receptor antagonist and synthase inhibitor DTTX30 on systemic and liver blood flow, oxygen (O2) exchange and energy metabolism during 24 h of hyperdynamic endotoxemia with untreated endotoxemia. Design: Prospective, randomized, experimental study with repeated measures. Setting: Investigational animal laboratory. Subjects: Twenty-seven domestic pigs: 16 during endotoxemia with volume resuscitation alone; 11 with endotoxemia, volume resuscitation and treatment with DTTX30. Interventions: Continuous infusion of Escherichia coli lipopolysaccharide (LPS) for 24 h together with volume resuscitation. After 12 h of endotoxemia, DTTX30 was administered as a bolus of 0.12 mg kg–1 followed by 12 h continuous infusion of 0.29 mg kg–1 per h. Measurements and results: DTTX30 effectively counteracted the endotoxin-associated increase in TXB2 levels and increased 6-keto-PGF1α with a significant shift of the thromboxane/prostacyclin ratio towards predominance of prostacyclin. DTTX30 prevented the significant progressive endotoxin-induced decrease of mean arterial pressure (MAP) below baseline while maintaining cardiac output (CO), and increased the fractional contribution of liver blood flow to CO without an effect on either hepatic O2 delivery or O2 uptake. The mean capillary hemoglobin O2 saturation (HbO2) on the liver surface and HbO2 frequency distributions remained unchanged as well. Conclusions: DTTX30 significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased the endogenous glucose production (EGP) rate, EGP returned towards baseline levels in the DTTX30-treated group. Thus, in our model DTTX30 resulted in hemodynamic stabilization concomitant with improved hepatic metabolic performance. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of a 12 h continuous infusion of iloprost, a stable prostacyclin analogue, on hepatic blood flow (Qliv), O2 exchange, and energy metabolism during a 24 h hyperdynamic, porcine endotoxemia with volume resuscitation alone.Design: Prospective, randomized, experimental study with repeated measures.Setting: Investigational animal laboratory.Subjects: Twenty-eight domestic pigs: 16 animals during endotoxemia with volume resuscitation alone (ETX), 12 with endotoxemia, volume resuscitation, and treatment with iloprost (ILO).Interventions: Endotoxemia was initiated by continuous infusion of E. coli lipopolysaccharide. Animals were resuscitated with hetastarch, aimed at maintaining a MAP of > 60 mmHg. After 12 h of endotoxemia, iloprost was administered for 12 h in the treatment group, titrated to avoid pharmacologically induced hypotension (MAP < 60 mmHg).Measurements and Results: Iloprost significantly increased Qliv, with no effect on hepatic O2 delivery. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface, as well as HbScO2 frequency distributions--a measure of microcirculatory O2 availability--remained unchanged. Treatment with iloprost, however, significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased endogenous glucose production (EGP) rate, iloprost restored EGP to normal at the end of the experiment.Conclusions: Thus, in a clinically relevant model of human sepsis, iloprost did not produce potential adverse effects but rather ameliorated hepatic metabolic disturbances and, thereby, hepatic energy balance. [ABSTRACT FROM AUTHOR]