Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?

Endotoxin shock was induced in 31 anaesthetized pigs by infusion of 5 μg/kg of Escbeicbia coli endotoxin (LPS) over 60 min into the superior mesenteric artery. Fifteen of these pigs died within 30 min of the start of LPS infusion whereas the remaining 16 survived the experimental period of 2 h. In a...

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Main Authors: T. Mózes, E. M. van Gelderen, E. J. Mylecharane, P. R. Saxena
Format: Article
Language:English
Published: Wiley 1995-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/S0962935195000202
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author T. Mózes
E. M. van Gelderen
E. J. Mylecharane
P. R. Saxena
author_facet T. Mózes
E. M. van Gelderen
E. J. Mylecharane
P. R. Saxena
author_sort T. Mózes
collection DOAJ
description Endotoxin shock was induced in 31 anaesthetized pigs by infusion of 5 μg/kg of Escbeicbia coli endotoxin (LPS) over 60 min into the superior mesenteric artery. Fifteen of these pigs died within 30 min of the start of LPS infusion whereas the remaining 16 survived the experimental period of 2 h. In a group of nine pigs indomethacin (2 mg/kg, i.v.)was inected 20–25 rain after the start of LPS infusion at which time mean arterial blood pressure (MABP) had decreased below 40 mmHg indicating imminent death. Indomethacin immediately reversed the hypotension. In another group of five pigs, NG-nitro L-arginine-methyl ester (L-NAME, 1 and 3 mg/kg)was iniected 10 and 5 min, respectively, before the expected death without any beneficial effect on the hypotension. Three rain after the last dose of L-NAME, indomethacin (2 mg/kg, i.v.) was iniected. In three animals the hypotension was reserved by indomethacin, although this beneficial effect was delayed in comparison with the LP-Streated group not receiving L-NAME. Four pigs were pretreated with L-NAME, 3 mg/kg, i.v., 10 min prior to LPS infusion. All pretreated animals tended to die within 30 min of the start of the LPS infusion. Five rain before the expected death (20–25 rain after the start of LPS infusion) indomethacin (2 mg/kg) was inected. In three of these animals indomethacin reversed hypotenston and prevented death. Interestingly, this rise in the MABP developed very slowly. These results suggest that the beneficial effect of indomethacin in endotoxin shock might be related partially to interference with nitric oxide, which is not the only factor determining blood pressure levels during endotoxic shock.
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spelling doaj-art-2eeecfb7315248b9a7ea5aa03b68345a2025-02-03T01:09:48ZengWileyMediators of Inflammation0962-93511466-18611995-01-014211712310.1155/S0962935195000202Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?T. Mózes0E. M. van Gelderen1E. J. Mylecharane2P. R. Saxena3Department of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Postbox 1738, Rotterdam 3000 DR, The NetherlandsDepartment of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Postbox 1738, Rotterdam 3000 DR, The NetherlandsDepartment of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Postbox 1738, Rotterdam 3000 DR, The NetherlandsDepartment of Pharmacology, Cardiovascular Research Institute ‘COEUR’, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Postbox 1738, Rotterdam 3000 DR, The NetherlandsEndotoxin shock was induced in 31 anaesthetized pigs by infusion of 5 μg/kg of Escbeicbia coli endotoxin (LPS) over 60 min into the superior mesenteric artery. Fifteen of these pigs died within 30 min of the start of LPS infusion whereas the remaining 16 survived the experimental period of 2 h. In a group of nine pigs indomethacin (2 mg/kg, i.v.)was inected 20–25 rain after the start of LPS infusion at which time mean arterial blood pressure (MABP) had decreased below 40 mmHg indicating imminent death. Indomethacin immediately reversed the hypotension. In another group of five pigs, NG-nitro L-arginine-methyl ester (L-NAME, 1 and 3 mg/kg)was iniected 10 and 5 min, respectively, before the expected death without any beneficial effect on the hypotension. Three rain after the last dose of L-NAME, indomethacin (2 mg/kg, i.v.) was iniected. In three animals the hypotension was reserved by indomethacin, although this beneficial effect was delayed in comparison with the LP-Streated group not receiving L-NAME. Four pigs were pretreated with L-NAME, 3 mg/kg, i.v., 10 min prior to LPS infusion. All pretreated animals tended to die within 30 min of the start of the LPS infusion. Five rain before the expected death (20–25 rain after the start of LPS infusion) indomethacin (2 mg/kg) was inected. In three of these animals indomethacin reversed hypotenston and prevented death. Interestingly, this rise in the MABP developed very slowly. These results suggest that the beneficial effect of indomethacin in endotoxin shock might be related partially to interference with nitric oxide, which is not the only factor determining blood pressure levels during endotoxic shock.http://dx.doi.org/10.1155/S0962935195000202
spellingShingle T. Mózes
E. M. van Gelderen
E. J. Mylecharane
P. R. Saxena
Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?
Mediators of Inflammation
title Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?
title_full Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?
title_fullStr Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?
title_full_unstemmed Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?
title_short Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?
title_sort beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide
url http://dx.doi.org/10.1155/S0962935195000202
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AT emvangelderen beneficialhaemodynamiceffectofindomethacinduringendotoxinshockinanaesthetizedpigsputativeinvolvementofnitricoxide
AT ejmylecharane beneficialhaemodynamiceffectofindomethacinduringendotoxinshockinanaesthetizedpigsputativeinvolvementofnitricoxide
AT prsaxena beneficialhaemodynamiceffectofindomethacinduringendotoxinshockinanaesthetizedpigsputativeinvolvementofnitricoxide