Models of Endotoxemia in Sheep

Traber, Daniel L.; Traber, L. D.; Redl, Heinz; Schlag, G.

doi:10.1007/978-3-642-76736-4_70

Cited by 8 publications

(7 citation statements)

References 77 publications

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“…In the control group, the changes in PAP and PAR followed a parallel course characterized by continuous increase, which attained significance by 1.5 and 2.5 h, respectively. The results are similar to those reported by other investigators [2][3][4]26]. Our data and those reported by others show that endotoxin causes pulmonary hypertension, but the mechanism has not been defined.…”

Section: Figsupporting

confidence: 94%

“…Lung injury induced by Escherichia coli endotoxin is characterized by pulmonary hypertension and increased microvascular permeability, resulting in the formation of pulmonary edema [1][2][3][4]. Experimental studies have reported salutary effects of fructose-1,6-diphosphate (FDP) in shock of different etiologies, including canine endotoxin shock [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Influence of Fructose-1,6-Diphosphate on Endotoxin-Induced Lung Injuries in Sheep

Markov

Warren

Cohly

et al. 2007

Journal of Surgical Research

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Section: Figsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Influence of Fructose-1,6-Diphosphate on Endotoxin-Induced Lung Injuries in Sheep

Markov

Warren

Cohly

et al. 2007

Journal of Surgical Research

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“…In accordance with earlier studies [16,17], hemodynamic parameters, including liver blood flow, gradually deteriorated during the infusion of endotoxin. The decreases in car diac output were parallelled by corresponding decreases in portal flow, and were not com pensated by increased hepatic arterial flow.…”

Section: Discussionsupporting

confidence: 66%

The NO Donor Sodium Nitroprusside Reverses the Negative Effects on Hepatic Arterial Flow Induced by Endotoxin and the NO Synthase Inhibitor L-NAME

Gundersen¹,

Sætre²,

Scholz³

et al. 1996

Eur Surg Res

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In previous studies we have observed that the nitric oxide synthase inhibitor L-NAME induces a profound deterioration of liver circulation in experimental endotoxemia. Using the same porcine model we now have evaluated the possibility of modulating these effects with the nitric oxide donor sodium nitroprusside. Infusion of endotoxin led to a gradual deterioration of hemodynamic parameters, including liver blood flow. The decreases in portal blood flow paralleled and matched the decreases in cardiac output, and no compensatory increase in hepatic arterial flow occurred. L-NAME had detrimental effects on hemodynamics, including the liver circulation. The latter effects could, however, partially be reversed by sodium nitroprusside. Hepatic arterial flow increased from 1.9 to 7.2 ml/kg/min, with a concomitant decrease in hepatic arterial resistance from 5,364 to 1,746 dyn s/cm5 kg. A control group exhibited no significant change in either flow or resistance. The response to sodium nitroprusside was rapid and vigorous, and probably largely due to relaxation of the hepatic arterioles, and not to abatement of intrahepatic edema or plugging of the sinusoids. Furthermore, we conclude that the endotoxin-induced dysfunction of the hepatic arterial buffer response may be due to a selective inhibition of vascular endothelial function.

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“…As reported previously by our group and others, increases in EVLWI in animals exposed to infusion of LPS are associated with enhanced pulmonary microvascular pressure [9,23,24]. However, none of these investigators have focused on the relationship between the plasma concentration of ET-1 and the pulmonary microvascular pressure.…”

Section: Discussionmentioning

confidence: 83%

Tezosentan-induced attenuation of lung injury in endotoxemic sheep is associated with reduced activation of protein kinase C

et al. 2005

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IntroductionStudies in vitro reveal that endothelin-1 (ET-1) activates the α isoform of protein kinase C (PKC-α) in cultures of endothelial cells, thereby deranging cellular integrity. Sepsis and endotoxemia are associated with increased plasma concentrations of ET-1 that induce acute lung injury (ALI). We recently reported that non-selective ET-1 receptor blockade attenuates ALI in sheep by reducing the endotoxin-induced increase in extravascular lung water index (EVLWI). The aim of this study was to find out whether this attenuation is associated with reduced translocation of PKC-α from the cytosolic to the membrane fraction of lung tissue homogenate.MethodsSeventeen awake, instrumented sheep were randomly assigned to a sham-operated group (n = 3), a lipopolysaccharide (LPS) group (n = 7) receiving an intravenous infusion of Escherichia coli 15 ng/kg per min for 24 hours, and a tezosentan group (n = 7) subjected to LPS and, from 4 hours, an intravenous injection of tezosentan 3 mg/kg followed by infusion at 1 mg/kg per hour for the reminder of the experiment. Pulmonary micro-occlusion pressure (Pmo), EVLWI, plasma concentrations of ET-1, tumor necrosis factor-a (TNF-a), and interleukin-8 (IL-8) were determined every 4 hours. Western blotting was used to assess PKC-α.ResultsIn non-treated sheep a positive correlation was found between the plasma concentration of ET-1 and Pmo in the late phase of endotoxemia (12 to 24 hours). A positive correlation was also noticed between Pmo and EVLWI in the LPS and the LPS plus tezosentan groups, although the latter was significantly reduced in comparison with LPS alone. In both endotoxemic groups, plasma concentrations of ET-1, TNF-α, and IL-8 increased. In the LPS group, the cytosolic fraction of PKC-α decreased by 75% whereas the membrane fraction increased by 40% in comparison with the sham-operated animals. Tezosentan completely prevented the changes in PKC-α in both the cytosolic and the membrane fractions, concomitantly causing a further increase in the plasma concentrations of ET-1, TNF-α, and IL-8.ConclusionIn endotoxemic sheep, ET-1 receptor blockade alleviates lung injury as assessed by a decrease in EVLWI paralleled by a reduction in Pmo and the prevention of activation of PKC-α.

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Models of Endotoxemia in Sheep

Cited by 8 publications

References 77 publications

Influence of Fructose-1,6-Diphosphate on Endotoxin-Induced Lung Injuries in Sheep

Influence of Fructose-1,6-Diphosphate on Endotoxin-Induced Lung Injuries in Sheep

The NO Donor Sodium Nitroprusside Reverses the Negative Effects on Hepatic Arterial Flow Induced by Endotoxin and the NO Synthase Inhibitor L-NAME

Tezosentan-induced attenuation of lung injury in endotoxemic sheep is associated with reduced activation of protein kinase C

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