Effects of 15-deoxy-Delta12,14-prostaglandin-J2 during hyperdynamic porcine endotoxemia.

Abstract:

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-Delta12,14-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-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). 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.

journal_name

Intensive Care Med

journal_title

Intensive care medicine

authors

Hauser B,Kick J,Iványi Z,Asfar P,Ehrmann U,Muth CM,Albicini M,Wachter U,Vogt J,Bauer M,Brückner UB,Radermacher P,Bracht H

doi

10.1007/s00134-006-0107-8

keywords:

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

759-65

issue

5

eissn

0342-4642

issn

1432-1238

journal_volume

32

pub_type

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