Gut-Lymph Hypothesis of Systemic Inflammatory Response Syndrome/Multiple-Organ Dysfunction Syndrome: Validating Studies in a Porcine Model

Senthil, Maheswari; Brown, Margaret; Xu, Da-Zhong; Lu, Quan; Feketeova, Eleonora; Deitch, Edwin A.

doi:10.1097/01.ta.0000215500.00018.47

Cited by 95 publications

(63 citation statements)

References 38 publications

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“…Through the bloodstream, bacteria, endotoxins, cells degradation products and activated immune cells translocate and promote SIRS. Cytokines, chemokines, cellular and bacterial debris can also reach the pulmonary circulation from the lymphatic circulation and thus cause acute respiratory distress syndromes [15,16]. The absence of a rapid recovery of a sufficient digestive perfusion leads to irreversible transmural necrosis and then to peritonitis.…”

Section: Multistep Pathophysiologymentioning

confidence: 99%

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Diagnosis biomarkers in acute intestinal ischemic injury: so close, yet so far

Peoc’h

Nuzzo

Guedj

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Acute intestinal ischemic injury (i3) is a lifethreatening condition with disastrous prognosis, which is currently difficult to diagnose at the early stages of the disease; a rapid diagnosis is mandatory to avoid irreversible ischemia, extensive bowel resection, sepsis and death. The overlapping protein expression of liver and gut related to the complex physiopathology of the disease, the heterogeneity of the disease and its relative rarity could explain the lack of a useful early biochemical marker of i3. Apart from non-specific biological markers of thrombosis, hypoxia inflammation, and infection, several more specific biomarkers in relation with the gut barrier dysfunction, the villi injury and the enterocyte mass have been used in the diagnosis of acute i3. It includes particularly D-lactate, intestinal fatty acid-binding protein (FABP) and citrulline. Herein, we will discuss leading publications concerning these historical markers that point out the main limitations reagrding their use in routine clinical practice. We will also introduce the first and limited results arising from omic studies, underlying the remaining effort that needs to be done in the field of acute i3 biological diagnosis, which remains a challenge.

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Section: Multistep Pathophysiologymentioning

confidence: 99%

“…The absence of a rapid recovery of a sufficient digestive perfusion leads to irreversible transmural necrosis and then to peritonitis. Without intestinal resection, the SIRS evolves to multiple organ syndrome and death [16].…”

Section: Multistep Pathophysiologymentioning

confidence: 99%

Diagnosis biomarkers in acute intestinal ischemic injury: so close, yet so far

Peoc’h

Nuzzo

Guedj

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Because gut dysfunction is a trigger in the pathogenesis of multiple organ failure (Moore, 1999;Rotstein, 2000;Senthil et al, 2006;Hauer-Jensen et al, 2007;Groschwitz and Hogan, 2009), there exists a need to address loss of barrier function early after traumatic injury. Apart from prompt and adequate resuscitation (Shi et al, 2002;Vega et al, 2008), no one specific medication alone is known to support circulatory deficit in hemorrhagic shock.…”

Section: Introductionmentioning

confidence: 99%

Remediation of Hemorrhagic Shock-Induced Intestinal Barrier Dysfunction by Treatment with Diphenyldihaloketones EF24 and CLEFMA

Yadav

Hussain

Sahoo

et al. 2014

The Journal of Pharmacology and Experimental Therapeutics

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Gut is very sensitive to hypoperfusion and hypoxia, and deranged gastrointestinal barrier is implicated in systemic failure of various organs. We recently demonstrated that diphenyldihaloketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one] improves survival in a rat model of hemorrhagic shock. In this study, we tested EF24 and its other analog CLEFMA (4-[3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid) for their effect on intestinal barrier dysfunction in hypovolemic shock. Hypovolemia was induced in rats by withdrawing 50% of blood. EF24 or CLEFMA (0.4 mg/kg i.p.) treatment was provided, without volume resuscitation, after 1 hour of hemorrhage. Ileum was collected 5 hours after the treatment to investigate the expression of tight junction proteins (zonula occludens, claudin, and occludin) and epithelial injury markers [myeloperoxidase, ileal lipid-binding protein (ILBP), CD163, and plasma citrulline]. The ileal permeability for dextran-fluoroisothiocyanate and Evan's blue dye was determined. EF24 and CLEFMA reduced the hypovolemiainduced plasma citrulline levels and the ileal expression of myeloperoxidase, ILBP, and CD163. The drugs also restored the basal expression levels of zonula occludens, claudin, and occludin, which were substantially deranged by hypovolemia. In ischemic ileum, the expression of phospho(tyrosine)-zonula occludens-1 was reduced, which was reinstated by EF24 and CLEFMA. In contrast, the drug treatments maintained the hypovolemia-induced expression of phospho(threonine)-occludin, but reduced that of phospho(tyrosine)-occludin. Both EF24 and CLEFMA treatments reduced the intestinal permeability enhanced by hypovolemia. EF24 and CLEFMA attenuate hypovolemic gut pathology and protect barrier function by restoring the status of tight junction proteins. These effects were observed in unresuscitated shock, implying the benefit of EF24 and CLEFMA in prehospital care of shock.

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“…[9][10][11][12] Clinical data show a positive correlation between excessive gut permeability and the extent of the injury in trauma in patients. [12][13][14] Given the role of collecting lymphatics in the transport of gut-derived bacterial products, cytokines, and inflammatory mediators, it is possible that disrupted pumping of mesenteric collecting lymphatics in intoxicated trauma victims may contribute to the greater prevalence of morbidity and mortality from traumatic injury in the alcohol-abusing population. 15 Contractility of lymphatic smooth muscle can be modulated by extrinsic (neural and humoral) and intrinsic (myogenic) factors.…”

mentioning

confidence: 99%

Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca²⁺] in Rat Mesenteric Lymphatic Vessels

Souza‐Smith

Kerut

Breslin

et al. 2015

Lymphatic Research and Biology

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Gut-Lymph Hypothesis of Systemic Inflammatory Response Syndrome/Multiple-Organ Dysfunction Syndrome: Validating Studies in a Porcine Model

Abstract: This large animal model validates rodent studies showing that the shock-injured gut releases biologically active factors into the mesenteric lymph and these factors activate neutrophils and injure endothelial cells.

Cited by 95 publications

References 38 publications

Diagnosis biomarkers in acute intestinal ischemic injury: so close, yet so far

Diagnosis biomarkers in acute intestinal ischemic injury: so close, yet so far

Remediation of Hemorrhagic Shock-Induced Intestinal Barrier Dysfunction by Treatment with Diphenyldihaloketones EF24 and CLEFMA

Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca²⁺] in Rat Mesenteric Lymphatic Vessels

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Gut-Lymph Hypothesis of Systemic Inflammatory Response Syndrome/Multiple-Organ Dysfunction Syndrome: Validating Studies in a Porcine Model

Abstract: This large animal model validates rodent studies showing that the shock-injured gut releases biologically active factors into the mesenteric lymph and these factors activate neutrophils and injure endothelial cells.

Cited by 95 publications

References 38 publications

Diagnosis biomarkers in acute intestinal ischemic injury: so close, yet so far

Diagnosis biomarkers in acute intestinal ischemic injury: so close, yet so far

Remediation of Hemorrhagic Shock-Induced Intestinal Barrier Dysfunction by Treatment with Diphenyldihaloketones EF24 and CLEFMA

Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca2+] in Rat Mesenteric Lymphatic Vessels

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Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca²⁺] in Rat Mesenteric Lymphatic Vessels