Pathogenesis of Hemorrhage-Induced Bacteria/Endotoxin Translocation in Rats Effects of Recombinant Bactericidal/Permeability-Increasing Protein

Yao, Yong-ming; Bahrami, Soheyl; Leichtfried, Guenther; Redl, Heinz; Schlag, G.

doi:10.1097/00000658-199504000-00011

Cited by 88 publications

(41 citation statements)

References 31 publications

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“…In addition, an increased susceptibility to endotoxin may take place during the posttraumatic phase accounting for pathophysiologic alterations triggered by even slight amounts of endotoxin [38]. In this respect, therapeutic intervention by the systemic administration of anti-endotoxin agents has been shown to almost neutralize the plasma endotoxin concentration, clearly providing protection to vital organs against hemorrhage-induced injury and mortality [39][40][41][42]. These findings imply that gut-derived endotoxemia not only occurs early in the ischemic episode but also plays an important role regarding morbidity and mortality due to severe hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Early Bacteremia/Endotoxemia and Inflammatory Responses after Trauma – Hemorrhage and Complement Activation in a Nonhuman Primate Model

et al. 2000

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There is criticism that the major line of evidence regarding posttraumatic inflammatory response and bacterial translocation has mainly come from experiments in rodents. The aim of this study was therefore to investigate the very early bacteremia/endotoxemia and inflammatory response in nonhuman primates.Six baboons were subjected to hemorrhagic shock (40 mm Hg mean arterial pressure) preceded by infusion of zymosan-activated plasma (to simulate trauma-associated complement activation) followed by reinfusion for 1 h. Measurements of complement and granulocyte (PMN) activation, cytokines of the inflammatory network, soluble cytokine receptors, and bacteria/endotoxin translocation (BT) were performed.There were significantly increased levels of PMN elastase, interleukin-6, and soluble tumor necrosis factor (TNF) receptors, but not of TNF. BT was evident from positive blood cultures, and from trendwise increased endotoxin plasma levels. Early liver damage was shown from elevated glutathione S-transferase (GST) plasma levels.Complement activation and hemorrhagic shock lead to an early inflammatory response together with bacteremia/endotoxemia as evidence of translocation from the gut already during the shock period in subhuman primates.

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Section: Discussionmentioning

confidence: 99%

Evidence for Early Bacteremia/Endotoxemia and Inflammatory Responses after Trauma – Hemorrhage and Complement Activation in a Nonhuman Primate Model

et al. 2000

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“…The liver also acts to clear and detoxify toxins and bacterial products entering via the portal vein from the gut. Previously, experimental strategies to decrease endotoxin [lipopolysaccharide (LPS)], an essential component of the outer membrane of gram-negative bacteria, improved survival and decreased the production of inflammatory cytokines after hemorrhage and resuscitation (7,50).…”

mentioning

confidence: 99%

Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation

Lehnert¹,

Uehara²,

Bradford³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation. Am J Physiol Gastrointest Liver Physiol 291: G456 -G463, 2006. First published May 18, 2006 doi:10.1152/ajpgi.00480.2005.-Hemorrhagic shock and resuscitation cause endotoxemia and hepatocellular damage. Because lipopolysaccharide-binding protein (LBP) enhances cellular responses to endotoxin, our aim was to determine whether LBP contributes to hemorrhage/resuscitation-induced injury by comparing LBP knockout and wild-type mice. Under pentobarbital anaesthesia, wild-type and LBP-deficient mice were hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer solution. Serum alanine aminotransferase (ALT) necrosis, neutrophil infiltration, and 4-hydroxynonenal by histology/ cytochemistry and stress kinase activation by immunoblot analysis were then determined. ALT in wild-type mice was 2,461 Ϯ 383 and 1,418 Ϯ 194 IU/l (means Ϯ SE), respectively, at 2 and 6 h after resuscitation versus sham ALT of 102 Ϯ 6 IU/l. In LBP-deficient mice, ALT was blunted at both time points to 1,108 Ϯ 340 and 619 Ϯ 171 IU/l (P Ͻ 0.05). Liver necrosis after 6 h was also attenuated from 3.5 Ϯ 0.8% in wild-type mice to 1.3 Ϯ 0.5% in LBP-deficient mice (P Ͻ 0.05). After hemorrhage/resuscitation, neutrophil infiltration increased 71% more in wild-type than LBP knockout mice. Similarly, hepatic 4-hydroxynonenal staining, indicative of lipid peroxidation, decreased from 33.8 Ϯ 4.5% in wild-type mice to 11.6 Ϯ 1.9% in knockout mice (P Ͻ 0.05).

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“…Moreover, JNK2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium [36], although JNK I is reported to mediate apical junction disassembly triggered by calcium depletion [37]. Impaired intestinal barrier function promoted by ]NK during H/R may therefore also lead to portal vein endotoxemia, activation of TLR4 with phosphorylation of MAPKs, and increased production of inflammatory cytokines and ROS by hepatic Kupffer cells [34,35,43,44]. Future studies will be needed to characterize how JNK2-dependent actions inside and outside hepatocytes contribute causally to liver injury, mitochondrial dysfunction, and development of MODS/SIRS after H/R.…”

Section: Decreased Oxidative Stress After Hemorrhage Andmentioning

confidence: 99%

Mitochondrial Permeability Transition in Pathogenesis of Hemorrhagic Injury: Targeted Therapy with Minocycline

Lemasters¹

2012

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE 2012 REPORT TYPE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERMedical University of South Carolina Charleston, SC 29425-0001 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTPatients that initially survi ve hemorrhage and resuscitation may develop a systemic infla mmatory response syndrome (SIRS) that lead s to injury and dysfun ction of vital orga ns (multiple organ dysfunction syndrome, MODS), particularl y to the liver and kidney. SIRS a nd MODS may involve m itochondrial dysfunction. Minocycline and doxycycline are tetracycline derivatives that are cytoprotective to liver, brain and other organs in various models of hypoxic, ischemic and oxidative stress, which may a ct by preserv ing mitochondrial function. We determined whether minocycline and doxycycline protect liver and kidney in a mouse model of hemorrhage and resuscitation. Minocycline and doxycycline each decreased liver enzymes and creatinine in the blood after hemorrhage/resuscitation compared to vehicle. Minocy cline and doxycycline also sig nificantly decreased liver necrosis and liver and kidney apoptosis. Lastly, minocycline protected against mitochondrial inner membrane permeabilization (mitochondrial permeability transition) occurring after HS/R and improved survival. In conclusion, minocycline and doxycycline when administered only after resu scitation decrease liver an d kidney injury a fter hemorrhage/resuscitation and improve survival. These safe and widely used agents mi ght be usefu l clinically to prevent SIRS and MODS after hemorrhagic shock. Despite improvements in evacuation, 35% of deaths from far forward battlefield injuries occur prior to arrival to a field hospital. Even after successful hemorrhagic resuscitation, late deaths from multiple organ failure occur in up to 50% of victims of severe multiple trauma...

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Pathogenesis of Hemorrhage-Induced Bacteria/Endotoxin Translocation in Rats Effects of Recombinant Bactericidal/Permeability-Increasing Protein

Cited by 88 publications

References 31 publications

Evidence for Early Bacteremia/Endotoxemia and Inflammatory Responses after Trauma – Hemorrhage and Complement Activation in a Nonhuman Primate Model

Evidence for Early Bacteremia/Endotoxemia and Inflammatory Responses after Trauma – Hemorrhage and Complement Activation in a Nonhuman Primate Model

Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation

Mitochondrial Permeability Transition in Pathogenesis of Hemorrhagic Injury: Targeted Therapy with Minocycline

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