ArticleScience translational medicine2013
Pancreatic digestive enzyme blockade in the intestine increases survival after experimental shock.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Prediction of sepsis mortality using metabolite biomarkers in the blood: a meta-analysis of death-related pathways and prospective validation.BMC medicine · 2020Pooled it
- Pancreatic Digestive Enzyme Dispersion into Human Organs Outside the Gastrointestinal Tract.Journal of proteome research · 2025Article
- Oxygen-Mediated Molecular Mechanisms Involved in Intestinal Ischemia and Reperfusion Injury.International journal of molecular sciences · 2025Review
- Cathepsin K cleavage of angiopoietin-2 creates detrimental Tie2 antagonist fragments in sepsis.The Journal of clinical investigation · 2025Article
- Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.Clinical and translational medicine · 2025Review
- Aging by autodigestion.PloS one · 2024Article
- Mechanically reinforced biotubes for arterial replacement and arteriovenous grafting inspired by architectural engineering.Science advances · 2022Article
- Chronic Critical Illness: Current Aspects of the Problem (Review).Sovremennye tekhnologii v meditsine · 2022Review
- Enteral gabexate mesilate improves volume requirements and autonomic cardiovascular function after experimental trauma/hemorrhagic shock in the absence of blood reperfusion.American journal of translational research · 2022Article
- Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients.Cellular and molecular bioengineering · 2021Article
- Detailed exploration of pathophysiology involving inflammatory status and bleeding symptoms between lipopolysaccharide- and tissue factor-induced disseminated intravascular coagulation in rats.International journal of hematology · 2021Article
- The Gut-Lung Axis in Systemic Inflammation. Role of Mesenteric Lymph as a Conduit.American journal of respiratory cell and molecular biology · 2021Review
- Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock.Frontiers in immunology · 2021Review
- Enhanced intestinal permeability and intestinal co-morbidities in heat strain: A review and case for autodigestion.Temperature (Austin, Tex.) · 2021Review
- A Modern View of the Interstitial Space in Health and Disease.Frontiers in veterinary science · 2020Review
- iTRAQ-Based Quantitative Proteomic Analysis of Intestines in Murine Polymicrobial Sepsis with Hydrogen Gas Treatment.Drug design, development and therapy · 2020Article
- Targeting Complement Pathways in Polytrauma- and Sepsis-Induced Multiple-Organ Dysfunction.Frontiers in immunology · 2019Review
- Challenge to the Intestinal Mucosa During Sepsis.Frontiers in immunology · 2019Review
- Role of using two-route ulinastatin injection to alleviate intestinal injury in septic rats.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2018Article
- Innate immune responses to trauma.Nature immunology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors--6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate, tranexamic acid, or aprotinin--into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multiorgan failure, which can be treated with protease inhibitors that are currently available for use in the clinic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.