Effects of 15-deoxy-Delta12,14-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-Delta12,14-prostaglandin-J2 (15d-PGJ2) during long-term, hyperdynamic porcine endotoxemia.


METHODS
Prospective, randomized, controlled experimental study with repeated measures.


METHODS
Investigational animal laboratory.


METHODS
19 anesthetized, mechanically ventilated and instrumented pigs.


METHODS
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).


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.
Hauser
Balázs
B
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Parkstrasse 11, 89073, Ulm, Germany.
Kick
Jochen
J
Iványi
Zsolt
Z
Asfar
Pierre
P
Ehrmann
Ulrich
U
Muth
Claus-Martin
CM
Albicini
Maura
M
Wachter
Ulrich
U
Vogt
Josef
J
Bauer
Michael
M
Brückner
Uwe Bernd
UB
Radermacher
Peter
P
Bracht
Hendrik
H
D000818:Animals; D003517:Cyclopentanes; D019446:Endotoxemia / Q000503:physiopathology*; D005060:Europe; D007022:Hypotension / Q000517:prevention & control; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D011446:Prospective Studies; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D011897:Random Allocation; D012121:Respiration, Artificial; D013552:Swine
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D003517:Cyclopentanes; D007155:Immunologic Factors; D011453:Prostaglandins; C013905:cyclopentenone; D015230:Prostaglandin D2