Hepatic oxygen exchange and energy metabolism in hyperdynamic porcine endotoxemia: effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX30
| Autor: | Peter Radermacher, Michael Georgieff, Carl Zülke, Arnim Vlatten, Ulrich Wachter, Uwe B. Brückner, K. W. Jauch, Martin Matejovic, Jürgen Altherr, Alexander Brinkmann, Josef Vogt, Karl Träger |
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| Rok vydání: | 2001 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Resuscitation Mean arterial pressure Cardiac output Pyridines Swine Thromboxane Drug Evaluation Preclinical Hemodynamics Prostacyclin Chlorobenzenes Critical Care and Intensive Care Medicine Statistics Nonparametric Hemoglobins Random Allocation Oxygen Consumption Internal medicine Pyruvic Acid Escherichia coli medicine Animals Prospective Studies Enzyme Inhibitors Escherichia coli Infections business.industry Antagonist Metabolism Endotoxemia Disease Models Animal Endocrinology Lactates Fluid Therapy Blood Gas Analysis Energy Metabolism business Liver Circulation medicine.drug |
| Zdroj: | Intensive Care Medicine. 27:416-425 |
| ISSN: | 1432-1238 0342-4642 |
| DOI: | 10.1007/s001340000839 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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