Protective effect of diclofenac sodium against endotoxic shock in anaesthetized pigs.
The effect of diclofenac sodium was investigated on haemodynamics, haematologic and blood glucose values as well as the release of eicosanoids, tumor necrosis factor (TNF) and platelet activating factor (PAF) in anaesthetized pigs receiving 5 micrograms.kg-1 Escherichia coli lipopolysaccharide (LPS) over 60 min into the superior mesenteric artery. The animals were observed for an additional period of 2 h after the termination of LPS infusion. 15 of the 31 animals infused with LPS and not treated with diclofenac sodium died within 30 min after the commencement of LPS infusion (non-survivors), while the other 16 survived the experimental period of 3-h, though in a shock state (survivors). No alterations were observed in plasma concentrations of PAF or eicosanoids (TXB2, 6-keto PGF1 alpha and LTB4), but a marked increase was detected in TNF release in the non-survivors. A significant, though transient, increase in concentrations of PAF, TNF and eicosanoids studied characterized the survivors. Another group of 7 LPS-infused pigs was treated with diclofenac sodium (2 mg, kg-1, i.v. bolus 60 min before the start of LPS infusion, followed by a continuous infusion of 1 mg kg-1 h-1) 1 mg/kg-1/h-1. This treatment prevented death and shock despite the high concentrations of TNF and PAF. Concentrations of both cyclooxygenase and 5-lipoxygenase enzymes products were reduced. These data indicated that the beneficial effect of diclofenac sodium in LPS induced shock may be related to the reduced production of eicosanoids.
Mózes
T
T
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Heiligers
J P
JP
Tak
C J
CJ
Zijlstra
F J
FJ
Ben-Efraim
S
S
Saxena
P R
PR
Bonta
I L
IL
D000818:Animals; D001772:Blood Cell Count; D001786:Blood Glucose / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology*; D015777:Eicosanoids / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D010972:Platelet Activating Factor / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001786:Blood Glucose; D015777:Eicosanoids; D006454:Hemoglobins; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D004008:Diclofenac