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- Title
Effects of 15-deoxy-Delta12,14-prostaglandin-J2 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
<bold>Objective: </bold>To investigate the hemodynamic and metabolic effects of the peroxisome proliferator-activated receptor (PPAR)-gamma ligand and nuclear-factor (NF)-kappa B inhibitor 15-deoxy-Delta12,14-prostaglandin-J2 (15d-PGJ2) during long-term, hyperdynamic porcine endotoxemia.<bold>Design: </bold>Prospective, randomized, controlled experimental study with repeated measures.<bold>Setting: </bold>Investigational animal laboratory.<bold>Subjects: </bold>19 anesthetized, mechanically ventilated and instrumented pigs.<bold>Interventions: </bold>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-Delta12,14-prostaglandin-J2 (15d-PGJ2 group, n=9; 1 microg kg(-1) min(-1) loading dose during 1 h; thereafter,0.25 microg kg(-1) min(-1) for 11 h).<bold>Measurements and Results: </bold>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).<bold>Conclusions: </bold>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
EUROPE; HYPOTENSION; ANIMAL experimentation; ARTIFICIAL respiration; COMPARATIVE studies; HYDROCARBONS; IMMUNOLOGICAL adjuvants; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; PROSTAGLANDINS; RESEARCH; STATISTICAL sampling; SWINE; OXIDATIVE stress; EVALUATION research; ENDOTOXEMIA; PHARMACODYNAMICS; PREVENTION
- Publication
Intensive Care Medicine, 2006, Vol 32, Issue 5, p759
- ISSN
0342-4642
- Publication type
journal article
- DOI
10.1007/s00134-006-0107-8