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.