Hemorrhagic Shock Increases Gut Macromolecular Permeability in the Rat

Russell, Diane Haddock; Barreto, José C.; Klemm, Klaus; Miller, Thomas A.

doi:10.1097/00024382-199507000-00008

Cited by 59 publications

(29 citation statements)

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“…If it is assumed that glycocalyx damage is systemic, the endothelial surface covered by the glycocalyx is large, and the glycocalyx is involved in various processes (65) including permeability (49) and mechanotransduction of fluid shear stress (65), the potential consequences of glycocalyx degradation are substantial. After ischemia and inflammation, glycocalyx shedding promotes neutrophil/leukocyte access to tissue (33,38), and a similar mechanism could be present during hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

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Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids

Filho

Torres

Salgado

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

104

108

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Torres Filho IP, Torres LN, Salgado C, Dubick MA. Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids. Am J Physiol Heart Circ Physiol 310: H1468 -H1478, 2016. First published April 1, 2016; doi:10.1152/ajpheart.00006.2016.-The endothelial glycocalyx plays an essential role in many physiological functions and is damaged after hemorrhage. Fluid resuscitation may further change the glycocalyx after an initial hemorrhage-induced degradation. Plasma levels of syndecan-1 and heparan sulfate have been used as indirect markers for glycocalyx degradation, but the extent to which these measures are representative of the events in the microcirculation is unknown. Using hemorrhage and a wide range of resuscitation fluids, we studied quantitatively the relationship between plasma biomarkers and changes in microvascular parameters, including glycocalyx thickness. Rats were bled 40% of total blood volume and resuscitated with seven different fluids (fresh whole blood, blood products, and crystalloids). Intravital microscopy was used to estimate glycocalyx thickness in Ͼ270 postcapillary venules from 58 cremaster preparations in 9 animal groups; other microvascular parameters were measured using noninvasive techniques. Systemic physiological parameters and blood chemistry were simultaneously collected. Changes in glycocalyx thickness were negatively correlated with changes in plasma levels of syndecan-1 (r ϭ Ϫ0.937) and heparan sulfate (r ϭ Ϫ0.864). Changes in microvascular permeability were positively correlated with changes in both plasma biomarkers (r ϭ 0.8, P Ͻ 0.05). Syndecan-1 and heparan sulfate were also positively correlated (r ϭ 0.7, P Ͻ 0.05). Except for diameter and permeability, changes in local microcirculatory parameters (red blood cell velocity, blood flow, and wall shear rate) did not correlate with plasma biomarkers or glycocalyx thickness changes. This work provides a quantitative framework supporting plasma syndecan-1 and heparan sulfate as valuable clinical biomarkers of glycocalyx shedding that may be useful in guiding resuscitation strategies following hemorrhage.

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Section: Discussionmentioning

confidence: 99%

“…Changes in microvascular permeability are observed during hemorrhagic shock (49). Since all resuscitation fluids can contribute to edema formation (39) and the glycocalyx is critically involved in determining transvascular exchange after resuscitation (66), a multifluid comparison with regard to permeability is of great interest.…”

Section: Discussionmentioning

confidence: 99%

Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids

Filho

Torres

Salgado

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

104

108

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“…Intestinal barrier dysfunction, manifested by increased mucosal permeability to hydrophilic macromolecules and/or increased bacterial translocation to mesenteric lymph nodes (MLN), occurs following hemorrhagic shock and resuscitation (HS/R) in rodents (6)(7)(8)(9)(10)(11)(12)(13). These findings may have clinical implications, because increased intestinal permeability has been shown to be associated with an increased risk of complications, MODS, or even mortality in critically ill patients (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Anti-HMGB1 Neutralizing Antibody Ameliorates Gut Barrier Dysfunction and Improves Survival after Hemorrhagic Shock

Yang

Harada

Mollen

et al. 2006

Mol Med

206

156

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Intestinal barrier dysfunction occurs following hemorrhagic shock and resuscitation (HS/R). High-mobility group B1 (HMGB1) has been shown to increase the permeability of Caco-2 human enterocyte-like epithelial monolayers in vitro. In this study, we found that serum concentrations of HMGB1 were higher in blood samples obtained from 25 trauma victims with hemorrhagic shock than in 9 normal volunteers. We also studied whether treatment with anti-HMGB1 antibody can ameliorate HS/R-induced gut barrier dysfunction in mice. Animals were shocked by withdrawal of blood to maintain mean arterial pressure at 25 to 30 mmHg for 2 h. After resuscitation with shed blood plus Ringer's lactate solution, the mice were treated with either anti-HMGB1 antibody or nonimmune rabbit IgG. Serum HMGB1 concentrations were significantly higher in trauma victims than control mice. Treatment with anti-HMGB1 antibody improved survival at 24 h and ameliorated the development of ileal mucosal hyperpermeability to FITC-labeled dextran. At 24 h after HS/R, treatment with anti-HMGB1 antibody decreased bacterial translocation to mesenteric lymph nodes and was associated with lower circulating concentrations of IL-6 and IL-10. These data support the notion that HMGB1 is a mediator of HS/R-induced gut barrier dysfunction and suggest that anti-HMGB1 antibodies warrant further evaluation as a therapeutic to ameliorate the morbidity of HS/R in trauma patients.

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“…An ischemic intestine is associated with elevated permeability [37,38,39,40,41] and therefore the usual compartmentalization of digestive enzymes in the lumen of the intestine may no longer be preserved. The question arises whether products generated during inadvertent entry of digestive enzymes into the wall of the intestine may cause an inflammatory reaction.…”

Section: The Intestine As Source Of Inflammatory Mediatorsmentioning

confidence: 99%

A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis

Schmid‐Schönbein

2007

International Immunopharmacology

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My association with Tony Hugli, long-term editor of Immunopharmacology and International Immunopharmacology, came about by a specific and long-standing problem in inflammation research. What is the trigger mechanism of inflammation in physiological shock? This is an important clinical problem due to the high mortality associated with physiological shock. We joined forces in the search of the answer to this question for more than a decade. Our journey eventually led to development of the hypothesis that shock may be associated with pancreatic enzymes, a set of powerful digestive enzymes that are an integral part of human digestion. The digestive enzymes need to be compartmentalized in the lumen of the intestine where they break down a broad spectrum of biological molecules into their building blocks, suitable for molecular transport across the mucosal epithelium into the circulation. The mucosal epithelial barrier is the key element for compartmentalization of the digestive enzymes. But under conditions when the mucosal barrier is compromised, the fully activated digestive enzymes in the lumen of the intestine are transported into the wall of the intestine, starting an auto-digestion process. In the process several classes of mediators are generated that by themselves have inflammatory activity and upon entry into the central circulation generate the hallmarks of inflammation and eventually cause multi-organ failure. Thus, our journey led to a new hypothesis, which is potentially of fundamental importance for death by multi-organ failure. The auto-digestion hypothesis is in line with the century old observation that the intestine plays a special role on shock -indeed it is the organ for digestion. Auto-digestion may be the prize to pay for life-long nutrition.

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Hemorrhagic Shock Increases Gut Macromolecular Permeability in the Rat

Cited by 59 publications

References 0 publications

Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids

Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids

Anti-HMGB1 Neutralizing Antibody Ameliorates Gut Barrier Dysfunction and Improves Survival after Hemorrhagic Shock

A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis

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