Effects of 15-deoxy-Δ12,14-prostaglandin-J2 during hyperdynamic porcine endotoxemia

Objective: 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-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) 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-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2) group, n = 9; 1 mu g kg(-1) min(-1) loading dose during 1 h; thereafter, 0.25 mu g 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-PGJ(2) 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-PGJ(2) 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-PGJ(2) concentrations and/or the delayed drug administration may explain these findings.