Pancreatic Duct Ligation Abrogates the Trauma Hemorrhage-Induced Gut Barrier Failure and the Subsequent Production of Biologically Active Intestinal Lymph

Caputo, Francis J.; Rupani, Bobby; Watkins, Anthony C.; Barlos, Dimitrios; Vega, David; Senthil, Maheswari; Deitch, Edwin A.

doi:10.1097/shk.0b013e31804858f2

Cited by 39 publications

(32 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus ischemia-reperfusion-mediated oxidative modification of the mucus may render the mucus layer susceptible to pancreatic digestive enzymes contained within the gut lumen. This notion is consistent with recent studies showing that pancreatic duct diversion of pancreatic enzymes from the intestinal lumen is associated with amelioration of T/HS-induced gut injury and preservation of both the intestinal mucus layer and gut barrier function (4). Thus, in the absence of pancreatic proteases in the gut lumen, T/HS-induced gut injury and dysfunction, as well as loss of the mucus layer, were largely abrogated.…”

Section: Discussionsupporting

confidence: 80%

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure

Fishman

Levy

Alli

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

View full text Add to dashboard Cite

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure. Am J Physiol Gastrointest Liver Physiol 304: G57-G63, 2013. First published November 1, 2012; doi:10.1152/ajpgi.00170.2012.-Recent studies demonstrate that mechanisms underlying gut barrier failure include systemic processes and less studied luminal processes. We thus tested the hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock-induced gut injury and dysfunction. Male Sprague-Dawley rats underwent trauma/hemorrhagic shock. Controls underwent trauma only. Mucus from the terminal 30 cm of the ileum was collected, processed, and analyzed for reactive nitrogen intermediates (RNI)-mediated damage, reactive oxygen species (ROS)-induced damage, and total antioxidant capacity. The distal ileum was stained to quantify the mucus layer; gut permeability was assessed physiologically. A time course study was conducted to determine the temporal sequence of mucus layer damage. The role of free radicalmediated damage to the gut barrier was investigated by the effect of the free radical scavenger dimethyl sulfoxide on trauma/hemorrhagic shock-induced changes on the mucus and on gut permeability. Trauma/hemorrhagic shock increased intestinal permeability, which was associated with evidence of loss of the unstirred mucus layer. These changes correlated with increased ROS-and RNI-mediated mucus damage and loss of mucus total antioxidant capacity. Based on the time course study, ROS-mediated mucus damage and loss of total antioxidant capacity were present immediately following shock, whereas RNI-mediated damage was delayed for 3 h. Dimethyl sulfoxide ameliorated gut barrier loss, ROS-mediated changes to the mucus layer, and loss of total antioxidant capacity. There was no change in RNI-induced changes to the mucus layer. These results support the hypothesis that trauma/hemorrhagic shock leads to mucus damage and gut dysfunction through the generation of free radical species.intestinal mucus layer; gut-mediated sepsis IN CERTAIN CLINICAL SCENARIOS, including major trauma and hemorrhage, gut injury and the subsequent loss of the gut barrier function have been implicated in the development of the acute respiratory distress syndrome, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome (8). Thus prevention or amelioration of gut injury in conditions associated with intestinal ischemia would be a key therapeutic strategy. Several such strategies, including early enteral nutrition, have been identified and instituted into clinical practice (1,20). However, the development of successful new clinical therapies is based on a complete knowledge of the mechanisms of the injuries they are being developed to treat. Consequently, a considerable amount of investigative attention has been committed to elucidating the pathogenesis of stress-and trauma/ shock-induced gut injury and gut barrier failure. These studies have largely focused on the ...

show abstract

Section: Discussionsupporting

confidence: 80%

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure

Fishman

Levy

Alli

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, the fact that the duct ligation model prevents pancreatic enzymes from reaching the gut lumen could help explain the lack of microscopic morphologic evidence of gut injury. Further support for the role of luminal pancreatic proteases in exacerbating gut injury comes from studies in a trauma-hemorrhagic shock model where pharmacologic neutralization of luminal pancreatic proteases (34) or pancreatic duct diversion (35) limited gut injury and preserved gut barrier function. On the other hand, our result suggest that the duration and magnitude of the ischemia-reperfusion insult was sufficient to cause injury to the mucus layer as well as loss of gut barrier function, despite the absence of intraluminal pancreatic proteases and evidence of microscopic morphologic gut injury.…”

Section: Discussionmentioning

confidence: 99%

The Intestinal Mucus Layer is a Critical Component of the Gut Barrier that is Damaged During Acute Pancreatitis

Fishman¹,

Levy²,

Alli³

et al. 2014

Shock

Self Cite

View full text Add to dashboard Cite

Background Gut barrier failure has been implicated in the progression from single organ injury to multiple organ failure. The unstirred mucus layer is a major component of the physiological gut barrier, its role in acute pancreatitis(AP) is not clearly defined. Study Design Rats underwent biliopancreatic duct ligation-induced AP; two controls were used: biliopancreatic duct ligation with drainage and sham duct ligation. After 4.5 hours, serum and ascitic amylase activity was measured. Mucus was analyzed for reactive nitrogen intermediates(RNI)-mediated damage, reactive oxygen species(ROS)-induced damage, and total antioxidant capacity. Mucus coverage and villous injury was assessed histologically. Ileum permeability was measured by diffusion of a fluorescent dextran probe. Histology and morphology of the mucus layer were validated in a mouse AP model (intraductal taurocholate plus caerulein). Results Biliopancreatic duct ligation increased serum α-amylase, ascitic volume, and ascitic α-amylase. Intestinal permeability was increased, which was associated with loss of the unstirred mucus layer but not villous injury. These changes correlated with increased ROS-and-RNI-mediated mucus damage as well as decreased mucus total antioxidant capacity but were not present in the two control groups. Using a different model of AP in mice, the finding of mucus layer disruption was recapitulated at 6 hours after AP, but by 24 hours, rebound hypersecretion of inspissated mucus was seen. Conclusions These results support the hypothesis that damage to the unstirred mucus layer with evidence of oxidative stress occurs during AP-induced gut barrier failure.

show abstract

“…The intestinal lymph pathway plays an important role in organ injuries in severe pathological conditions, such as hemorrhagic and traumatic shock and acute pancreatitis 5,15 . The report form Sambol et al 8 found that MLDL could prevent trauma/ hemorrhage shock-induced increases in LVDP and ±dP/dt max of isolated hearts form trauma/hemorrhage shocked rats.…”

Section: Discussionmentioning

confidence: 99%

Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock

Si-hai

Zhao

et al. 2015

Acta Cir. Bras.

View full text Add to dashboard Cite

PURPOSE:To evaluate whether post-hemorrhagic shock mesenteric lymph (PSML) is involved in cardiac dysfunction induced by hemorrhagic shock. METHODS:The hemorrhagic shock model (40±2 mmHg, 3h) was established in rats of the shock and shock+drainage groups; and PSML drainage was performed from hypotension 1-3h in the shock+drainage rats. Then, the isolated hearts were obtained from the rats for the examination of cardiac function with Langendorff system. Subsequently, the isolated hearts were obtained from normal rats and perfused with PSML or Krebs-Henseleit solution, and the changes of cardiac function were observed. RESULTS:The left ventricular systolic pressure (LVSP) and the maximal rates of LV developed pressure (LVDP) rise and fall (±dP/ dt max ) in the shock and shock+drainage groups were lower than that of the sham group; otherwise, these indices in the shock+drainage group were higher compared to the shock group. In addition, after isolated hearts obtained from normal rats perfusing with PSML, these cardiac function indices were gradual decline along with the extension of time, such as heart rate, LVSP, ±dP/dt max , etc. CONCLUSION:Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock.

show abstract

Pancreatic Duct Ligation Abrogates the Trauma Hemorrhage-Induced Gut Barrier Failure and the Subsequent Production of Biologically Active Intestinal Lymph

Cited by 39 publications

References 28 publications

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure

The Intestinal Mucus Layer is a Critical Component of the Gut Barrier that is Damaged During Acute Pancreatitis

Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock

Contact Info

Product

Resources

About