Increased Intestinal Permeability in Endotoxic Pigs

Fink, Mitchell P.; Antonsson, J. B.; Wang, Hailong; Rothschild, Heidie R.

doi:10.1001/archsurg.1991.01410260101014

Cited by 149 publications

(22 citation statements)

References 24 publications

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“…However, some animal studies provided negative evidence (21,22), e.g. uptake of amino acids by everted gut sacs prepared from septic animals was significantly reduced (21).…”

Section: Effects Of Lps Treatment On the Dynamics Of Plasma Free Bcaamentioning

confidence: 99%

The Effects of Endotoxin on Plasma Free Amino Acid Concentrations in Rats

Asai

Bajotto

Yoshizato

et al. 2008

J Nutr Sci Vitaminol

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SummaryWe examined the effects of lipopolysaccharide (LPS) injection on body temperature and plasma free amino acid concentrations in rats. A catheter was placed in the jugular vein of the rats in order to draw blood from and to inject LPS into awake animals. On the day of the experiment, body temperature was recorded during the experiment (330 min) and blood was drawn before and at several time points after injection of LPS (10 g/kg body weight). Body temperature in LPS-treated rats began to rise ~30 min after injection with a peak at 120 min, and afterward remained ~1˚C higher than that in control rats through the end of the experiment. Concentrations of many plasma free amino acids were decreased by LPS treatment, with a nadir at ~120 min, and then were increased to the level of or over the control. It appears that thermoregulatory responses induced by LPS treatment may be related to alterations in plasma free amino acid concentrations. Effects of LPS treatment on the dynamics of plasma free branched-chain amino acid (BCAA) concentrations in rats with peroral or intravenous administration of BCAAs were also examined. The results showed that the rise in plasma BCAA concentrations after peroral BCAA administration was significantly suppressed by LPS treatment, but the dynamics of plasma BCAAs after intravenous administration was not affected by LPS, suggesting that LPS treatment inhibited the intestinal absorption of BCAAs into the circulation. These results suggest that the availability of administered BCAAs to the body tissues during sepsis is higher following parenteral than peroral administration. Key Words endotoxin, lipopolysaccharide, plasma amino acids, branched-chain amino acids (BCAA), body temperature Sepsis induces several metabolic responses including negative nitrogen balance and loss of lean body mass. This catabolic phase is associated with muscle protein breakdown ( 1 , 2 ) and increased whole body amino acid metabolism ( 3 ). Glutamine metabolism and branchedchain amino acid (BCAA) catabolism are especially prominent; glutamine production is increased through proteolysis and BCAAs are actively oxidized in skeletal muscles during sepsis ( 4 , 5 ). Therefore, administration of these amino acids is considered to have a potential to alleviate the septic conditions ( 6 , 7 ).Administration of bacterial lipopolysaccharide (LPS) preparations to laboratory animals is widely used to reproduce the septic state, in which various metabolic as well as thermoregulatory responses are induced in association with systemic inflammation. It has been reported that the thermoregulatory response to LPS administration is dependent upon the dose of LPS and ambient temperature ( 8 ). In many studies ( 5 , 9 -12 ), high, shock-inducing doses such as 500 g LPS/kg body weight (BW) or more have been used and these doses caused pronounced hypothermia ( 8 ). On the other hand, it has been reported that intravenous administration of low or intermediary doses (less than 10 g/kg BW) of LPS elicits fever when animals are kept i...

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“…However, some animal studies provided negative evidence (21,22), e.g. uptake of amino acids by everted gut sacs prepared from septic animals was significantly reduced (21).…”

Section: Effects Of Lps Treatment On the Dynamics Of Plasma Free Bcaamentioning

confidence: 99%

The Effects of Endotoxin on Plasma Free Amino Acid Concentrations in Rats

Asai

Bajotto

Yoshizato

et al. 2008

J Nutr Sci Vitaminol

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“…81 Hypoperfusion per se contributes, but is not indepedently sufficient to account for all mesenteric permeability mechanisms. 82 However, hypoperfusion as well as pro-inflammatory cytokines are triggers for epithelial cellular apoptosis, all of which are putative incriminating agents/events in sepsis-induced gut hyperpermeability. Intestinal epithelial apoptosis in human sepsis 83 can in fact compromise mucosal integrity whereas Bcl-2 intestinal overexpression is partially protective in mice challenged with Pseudomonas aeruginosa pneumonia.…”

Section: The Intestine In Sepsismentioning

confidence: 99%

Review article: Organ per fusion/permeabilityrelated effects of norepinephrine and vasopressin in sepsis

Farand¹,

Hamel

Lauzier

et al. 2006

Can J Anesth/J Can Anesth

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Purpose:One invariable hallmark of severe sepsis is generalized tissue "malperfusion" and hyperpermeability secondary to microcirculatory/capillary leakage. This review focuses on direct and/or indirect influences of norepinephrine, as a standard of care, and vasopressin, as an alternative vasoactive drug, on organ and tissue perfusion/permeability in severe sepsis.Source: English and French language articles and books published between 1966 and 2005 were identified through a computerized Medline search using the terms "sepsis, permeability, norepinephrine and vasopressin". Relevant publications were retrieved and scanned for additional sources. Principal findings:There are few randomized clinical trials comparing different vasopressors in sepsis; most available literature consists of clinical reports, animal experiments and occasional reviews. Based on the best current evidence from these sources, we describe the status of major organ perfusion/ permeability in sepsis (i.e., the lung, the kidney, the heart, the intestine/gut) in the context of sepsis-induced organ dysfunction/failure. Potential and differential therapeutic effects of the vasopressors norepinephrine and arginine-vasopressin, in the setting of sepsis, are identified. Conclusions:In the treatment of sepsis, arginine-vasopressin exhibits organ-specific heterogeneity in vascular responsiveness, compared to norepinephrine. While norepinephrine is a current standard of care in sepsis, arginine-vasopressin shows promise for the treatment of septic shock. Objectif

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“…Infections develop in as many as one-third of all patients admitted to surgical intensive care units and are associated with increased mortality and a significant prolongation of intensive care unit stays [18]. Although the pathophysiology of sepsis, septic shock, and multiple organ failure remains elusive, much evidence has been accumulated implicating increased vasopermeability with altered endothelial cell function in the pathologic process [19,20]. Early studies concentrated on the bacteria and their products or byproducts in the pathophysiology of sepsis, but more recent studies have indicated that the immunologic response, mounted in response to the inciting agent(s), may have a detrimental effect on normal homeostasis [5,21,22].…”

Section: Discussionmentioning

confidence: 99%