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- Title
Effects of 15-deoxy-Δ<sup>12,14</sup>-prostaglandin-J<sub>2</sub> during hyperdynamic porcine endotoxemia.
- Authors
Hauser, Balázs; Kick, Jochen; Iványi, Zsolt; Asfar, Pierre; Ehrmann, Ulrich; Muth, Claus-Martin; Albicini, Maura; Wachter, Ulrich; Vogt, Josef; Bauer, Michael; Brückner, Uwe Bernd; Radermacher, Peter; Bracht, Hendrik
- Abstract
Objective: To investigate the hemodynamic and metabolic effects of the peroxisome proliferator-activated receptor (PPAR)-γ ligand and nuclear-factor (NF)-κ B inhibitor 15-deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2) during long-term, hyperdynamic porcine endotoxemia. Design: Prospective, randomized, controlled experimental study with repeated measures. Setting: Investigational animal laboratory. Subjects: 19 anesthetized, mechanically ventilated and instrumented pigs. Interventions: At 12 h of continuous intravenous endotoxin and hydroxyethylstarch to keep mean arterial pressure (MAP) > 60 mmHg, swine randomly received vehicle (control group, n = 10) or 15-deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2 group, n = 9; 1 µg kg-1 min-1loading dose during 1 h; thereafter, 0.25 µg kg-1 min-1 for 11 h). Measurements and results: Hemodynamic, metabolic and organ function parameters were assessed together with parameters of nitric oxide production and oxidative stress. 15d-PGJ2 prevented the endotoxin-induced progressive hypotension, due to a positive inotropic effect, which resulted in a significantly higher blood pressure during the treatment phase and prevented the rise in hepatic vein alanine-aminotransferase activity. It did not affect, however, any other parameter of organ function nor of nitric oxide production, proinflammatory cytokine release or lipid peroxidation (8-isoprostane). Conclusions: 15d-PGJ2 stabilized systemic hemodynamics, due to improved myocardial performance, and resulted in an only transient effect on alanine-aminotransferase activity, without further beneficial effect on endotoxin-induced metabolic and organ function derangements. Low tissue 15d-PGJ2 concentrations and/or the delayed drug administration may explain these findings.
- Subjects
HEMODYNAMICS; PEROXISOMES; PROSTAGLANDINS; NF-kappa B; ENDOTOXINS
- Publication
Intensive Care Medicine, 2006, Vol 32, Issue 5, p759
- ISSN
0342-4642
- Publication type
Article
- DOI
10.1007/s00134-006-0107-8