Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass?

Martinez-Pellús, Antonio E.; Merino, P.; Bru, Mariano; Conejero, R.; Seller, G.; Muñoz, Carlos; Fuentes, T.; González, Guillermo; Alvarez, B.

doi:10.1097/00003246-199311000-00017

Cited by 119 publications

(50 citation statements)

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“…How-ever, during and after bacterial killing or when translocated from the lumen of the intestine, LPS unassociated with worsening infection can induce inappropriate (toxic) levels of cellular mediators that trigger pathophysiological events such as hypotension, fever, shock, and coagulopathies (Bone, 1991a,b;Ulevitch and Tobias, 1995;Morrison, 1998;Norimatsu and Morrison, 1998;Suffredini and O'Grady, 1999) often leading to multiorgan failure and death (Brandtzaeg et al, 2001). Intestinal tract-derived endotoxin has been implicated as the cause of a variety of clinical manifestations such as postsurgical inflammatory response after abdominal aortic aneurysm (Roumen et al, 1993;Lau et al, 2000) and coronary artery bypass grafting (Martinez-Pellus et al, 1993), hepatic diseases such as alcoholic cirrhosis (Yin et al, 2001), and aggravation of inflammatory diseases such as graft versus host disease (Cooke et al, 2001) and inflammatory bowel disease (Gardiner et al, 1995).…”

Section: Similar To (6-o-{2-deoxy-6-o-methyl-4-o-phosphono-3-o-[(r)-3mentioning

confidence: 99%

Inhibition of Endotoxin Response by E5564, a Novel Toll-Like Receptor 4-Directed Endotoxin Antagonist

Mullarkey

Rose²,

Bristol³

et al. 2002

J Pharmacol Exp Ther

274

232

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␣-D-Glucopyranose,3-O-decyl-2-deoxy-6-O-[2-deoxy-3-O-[(3R)-3-methoxydecyl]-6-O-methyl-2-[[(11Z)-1-oxo-11-octadecenyl]amino]-4-O-phosphono-␤-D-glucopyranosyl]-2- [(1,3-dioxotetradecyl)amino]-1-(dihydrogen phosphate), tetrasodium salt (E5564) is a second-generation synthetic lipodisaccharide designed to antagonize the toxic effects of endotoxin, a major immunostimulatory component of the outer cell membrane of Gram negative bacteria. In vitro, E5564 dose dependently (nanomolar concentrations) inhibited lipopolysaccharide (LPS)-mediated activation of primary cultures of human myeloid cells and mouse tissue culture macrophage cell lines as well as human or animal whole blood as measured by production of tumor necrosis factor-␣ and other cytokines. E5564 also blocked the ability of Gram negative bacteria to stimulate human cytokine production in whole blood. In vivo, E5564 blocked induction of LPS-induced cytokines and LPS or bacterial-induced lethality in primed mice. E5564 was devoid of agonistic activity when tested both in vitro and in vivo and has no antagonistic activity against Gram positive-mediated cellular activation at concentrations up to 1 M. E5564 blocked LPSmediated activation of nuclear factor-B in toll-like receptor 4/MD-2-transfected cells. In a mouse macrophage cell line, activity of E5564 was independent of serum, suggesting that E5564 exerts its activity through the cell surface receptor(s) for LPS, without the need for serum LPS transfer proteins. Similar, another lipid A-like antagonist, E5564 associates with plasma lipoproteins, causing low concentrations of E5564 to be quantitatively inactivated in a dose-and time-dependent manner. However, compared with E5531, E5564 is a more potent inhibitor of cytokine generation, and higher doses retain activity for durations likely sufficient to permit clinical application. These results indicate that E5564 is a potent antagonist of LPS and lacks agonistic activity in human and animal model systems, making it a potentially effective therapeutic agent for treatment of disease states caused by endotoxin.

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Section: Similar To (6-o-{2-deoxy-6-o-methyl-4-o-phosphono-3-o-[(r)-3mentioning

confidence: 99%

Inhibition of Endotoxin Response by E5564, a Novel Toll-Like Receptor 4-Directed Endotoxin Antagonist

Mullarkey

Rose²,

Bristol³

et al. 2002

J Pharmacol Exp Ther

274

232

View full text Add to dashboard Cite

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“…MARTINEZ-PELLUS et al [53] demonstrated a decrease in blood levels of endotoxaemia in patients undergoing cardiac surgery (a model representing ischaemia-reperfusion) when administering full SDD regimens, including intravenous cefotaxime. Further studies are needed to prove the efficacy of gut decontamination to prevent VAP related to bacterial translocation.…”

Section: Bacterial Translocationmentioning

confidence: 99%

Stomach as a source of colonization of the respiratory tract during mechanical ventilation: association with ventilator-associated pneumonia

Torres

El-Ebiary²,

Soler³

et al. 1996

Eur Respir J

103

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The aetiopathogenesis of ventilator-associated pneumonia (VAP) requires abnormal oropharyngeal and gastric colonization and the further aspiration of their contents to the lower airways. VAP develops easily if aspiration or inoculation of microorganisms occur in patients with artificial airways, in whom mechanical, cellular and/or humoral defences are altered.Well-known risk factors for gastric colonization include: alterations in gastric juice secretion; alkalinization of gastric contents; administration of enteral nutrition; and the presence of bilirubin. However, the role of the colonized gastric reservoir in the development of VAP remains debatable.Evidence in favour of the role of the stomach in the development of VAP comes mainly from randomized, controlled trials of selective gut decontamination and stress ulcer prophylaxis in the intensive care unit (ICU), in which reducing the bacterial burden of the stomach decreases the incidence of nosocomial respiratory infections. However, at least three studies of flora have found an absence of stomach origin of pneumonia occurring during mechanical ventilation.Prophylactic measures suggested to prevent VAP in relation to the gastric reservoir include: treatment for stress ulcers with sucralfate; prevention of duodenal reflux with metoclopramide; reduction of gastric burden and bacterial translocation by selective digestive decontamination; acidification of enteral feeding; and jejunal feeding. Gastro-oesophageal reflux can be prevented by using small bore nasogastric tubes and jejunal feeding. The aspiration of gastric contents can be reduced by positioning patients in a semirecumbent position, checking the patency of the tube cuff, and aspiration of subglottic secretions.The role of the stomach as a reservoir for microorganisms causing ventilatorassociated pneumonia is still controversial but despite the debate, there is major evidence in the literature in favour of the gastric origin of part of these pulmonary infections.

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“…Obwohl in den vergangengen Jahren die Mehrzahl der durchgeführten Studien zu dem Ergebnis kamen, daß eine systemische Inflammation mit Freisetzung von überwiegend proinflammatorischen Zytokinen ("SIRS durch EKZ") für die Pathophysiologie des Multiorgan-Dysfunktions-Syndroms (MODS) verantwortlich zu sein scheint [8,20,26,27], geben die Ergebnisse neuerer Untersuchungen Anlaß zu der Erkenntnis, daß auch eine initiale antiinflammatorische Antwort des Organismus für die bereits erwähnten Organschäden und eine gestörte Immunfunktion mitverantwortlich gemacht werden muß [17,25]. Insbesondere nach Anwendung der EKZ konnten verschiedene Arbeitsgruppen eine Freisetzung von proinflammatorischen (TNF, IL-1, ethanolamide (LK 544) did not influence the LPS-stimulated release of the cytokines studied.…”

Section: Influence Of Gamma-hydroxybutyrate (Ghb) On Proinflammatory unclassified

“…Ob die tersucht. In Übereinstimmung mit verschiedenen Arbeitsgruppen wurde periund postopoerativ eine im Vergleich zum präoperativen Ausgangswert signifikant erhöhte spontane Freisetzung von IL-6 beobachtet, während TNF und IL-1β nicht in signifikantem Maße freigesetzt wurden [8,20,22,24]. Diese Befunde bei Eingriffen mit EKZ wurden bisher als Hinweis für die Aktivierung immunkompetenter Zellen (z.B.…”

Section: Diskussionunclassified

Einfluß von Gamma- Hydroxy-Buttersäure (GHB) auf die proinflammatorische Zytokin-Genexpression bei koronarchirurgischen Eingriffen

et al. 1998

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The results suggest a biphasic response of stimulated PBMC cytokine gene expression during CABG with an initial tolerance to LPS-stimulation shortly after termination of ECC. However, whether or not PBMC express functional GHB receptors remains unclear in light of contradictory effects of the different ligands. In spite of the ex vivo and in vitro results, application of GHB-Na in doses which are primarily based on its use as an anesthetic agent do not seem to modulate the release of the cytokines studied.

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Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass?

Cited by 119 publications

References 0 publications

Inhibition of Endotoxin Response by E5564, a Novel Toll-Like Receptor 4-Directed Endotoxin Antagonist

Inhibition of Endotoxin Response by E5564, a Novel Toll-Like Receptor 4-Directed Endotoxin Antagonist

Stomach as a source of colonization of the respiratory tract during mechanical ventilation: association with ventilator-associated pneumonia

Einfluß von Gamma- Hydroxy-Buttersäure (GHB) auf die proinflammatorische Zytokin-Genexpression bei koronarchirurgischen Eingriffen

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