scholarly journals Damage-associated molecular patterns in resuscitated hemorrhagic shock are mitigated by peritoneal fluid administration

2018 ◽  
Vol 315 (3) ◽  
pp. L339-L347
Author(s):  
Paul J. Matheson ◽  
Mark A. Eid ◽  
Matthew A. Wilson ◽  
Victoria S. Graham ◽  
Samuel A. Matheson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hemorrhagic Shock ◽  
Tissue Injury ◽  
High Mobility ◽  
Primary Response ◽  
Sprague Dawley ◽  
Shed Blood ◽  
Lung Blood Flow ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Conventional resuscitation (CR) of hemorrhagic shock (HS), a significant cause of trauma mortality, is intravenous blood and fluids. CR restores central hemodynamics, but vital organ flow can drop, causing hypoperfusion, hypoxia, damage-associated molecular patterns (DAMPs), and remote organ dysfunction (i.e., lung). CR plus direct peritoneal resuscitation (DPR) prevents intestinal and hepatic hypoperfusion. We hypothesized that DPR prevents lung injury in HS/CR by altering DAMPs. Anesthetized male Sprague-Dawley rats were randomized to groups ( n = 8/group) in one of two sets: 1) sham (no HS, CR, or DPR), 2) HS/CR (HS = 40% mean arterial pressure (MAP) for 60 min, CR = shed blood + 2 volumes normal saline), or 3) HS/CR + DPR. The first set underwent whole lung blood flow by colorimetric microspheres. The second set underwent tissue collection for Luminex, ELISAs, and histopathology. Lipopolysaccharide (LPS) and DAMPs were measured in serum and/or lung, including cytokines, hyaluronic acid (HA), high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 protein (MYD88), and TIR-domain-containing adapter-inducing interferon-β (TRIF). Statistics were by ANOVA and Tukey-Kramer test with a priori P < 0.05. HS/CR increased serum LPS, HA, HMGB1, and some cytokines [interleukin (IL)-1α, IL-1β, IL-6, and interferon-γ]. Lung TLR4 and MYD88 were increased but not TRIF compared with Shams. HS/CR + DPR decreased LPS, HA, cytokines, HMGB1, TLR4, and MYD88 levels but did not alter TRIF compared with HS/CR. The data suggest that gut-derived DAMPs can be modulated by adjunctive DPR to prevent activation of lung TLR-4-mediated processes. Also, DPR improved lung blood flow and reduced lung tissue injury. Adjunctive DPR in HS/CR potentially improves morbidity and mortality by downregulating the systemic DAMP response.

Decreases in organ blood flows associated with increases in sublingual P CO 2 during hemorrhagic shock

1998 ◽  
Vol 85 (6) ◽  
pp. 2360-2364 ◽  
Author(s):  
Xiaohua Jin ◽  
Max Harry Weil ◽  
Shijie Sun ◽  
Wanchun Tang ◽  
Joe Bisera ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hemorrhagic Shock ◽  
Esophageal Wall ◽  
Sprague Dawley ◽  
Shed Blood ◽  
Blood Flows ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Arterial Blood Lactate ◽  
Highly Correlated

Earlier studies demonstrated that not only the stomach but also the esophageal wall served as an appropriate site for estimating the severity of circulatory shock by using tonometric methods. We then conceived of the option of sublingual tonometry. In the present study, we tested the hypothesis that the changes in sublingual [Formula: see text] serve as indicators of decreases in blood flow to sublingual and visceral tissue. In Sprague-Dawley rats, sublingual[Formula: see text] increased from 50 to 127 Torr and arterial blood lactate increased from 0.9 to 11.2 mmol/l during bleeding. Sublingual blood flow simultaneously decreased to ∼32% of preshock values. After reinfusion of shed blood, organ blood flows and sublingual [Formula: see text] were promptly restored to near-baseline values. There were corresponding decreases in blood flows in the tongue, stomach, jejunum, colon, and kidneys during hemorrhagic shock. Increases in sublingual[Formula: see text] were highly correlated with decreases in sublingual blood flow ( r= 0.80), tongue blood flow ( r = 0.81), gastric blood flow ( r = 0.74), jejunal blood flow ( r = 0.65), colon blood flow ( r = 0.80), and renal blood flow ( r = 0.75). Unbled control animals demonstrated no significant changes. Therefore, we anticipate that sublingual tonometry will provide a useful, noninvasive alternative for monitoring visceral [Formula: see text].

scholarly journals Role of Damage-Associated Molecular Patterns in Septic Acute Kidney Injury, From Injury to Recovery

2021 ◽  
Vol 12 ◽  
Author(s):  
Pierre-Olivier Ludes ◽  
Charles de Roquetaillade ◽  
Benjamin Glenn Chousterman ◽  
Julien Pottecher ◽  
Alexandre Mebazaa
Keyword(s):  
Acute Kidney Injury ◽  
Tissue Injury ◽  
High Mobility ◽  
Kidney Injury ◽  
Blood Perfusion ◽  
Tubular Damage ◽  
Organ Protection ◽  
Tubular Necrosis ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Damage-associated molecular patterns (DAMPs) are a group of immunostimulatory molecules, which take part in inflammatory response after tissue injury. Kidney-specific DAMPs include Tamm-Horsfall glycoprotein, crystals, and uromodulin, released by tubular damage for example. Non-kidney-specific DAMPs include intracellular particles such as nucleus [histones, high-mobility group box 1 protein (HMGB1)] and cytosol parts. DAMPs trigger innate immunity by activating the NRLP3 inflammasome, G-protein coupled class receptors or the Toll-like receptor. Tubular necrosis leads to acute kidney injury (AKI) in either septic, ischemic or toxic conditions. Tubular necrosis releases DAMPs such as histones and HMGB1 and increases vascular permeability, which perpetuates shock and hypoperfusion via Toll Like Receptors. In acute tubular necrosis, intracellular abundance of NADPH may explain a chain reaction where necrosis spreads from cell to cell. The nature AKI in intensive care units does not have preclinical models that meet a variation of blood perfusion or a variation of glomerular filtration within hours before catecholamine infusion. However, the dampening of several DAMPs in AKI could provide organ protection. Research should be focused on the numerous pathophysiological pathways to identify the relative contribution to renal dysfunction. The therapeutic perspectives could be strategies to suppress side effect of DAMPs and to promote renal function regeneration.

Differing effects of anesthetics on splanchnic arterial blood flow during hemorrhagic shock

1994 ◽  
Vol 76 (6) ◽  
pp. 2304-2309 ◽  
Author(s):  
S. I. Myers ◽  
R. Hernandez ◽  
T. A. Miller
Keyword(s):  
Blood Flow ◽  
Hemorrhagic Shock ◽  
Arterial Blood Flow ◽  
Splanchnic Blood Flow ◽  
Aortic Blood Flow ◽  
Sprague Dawley ◽  
Acute Hemorrhage ◽  
Shed Blood ◽  
Arterial Blood ◽  
Aortic Blood

The effect of anesthesia on splanchnic blood flow was examined during hemorrhagic shock and resuscitation. Sprague-Dawley rats were anesthetized with the inhalation anesthetic, methoxyflurane, or pentobarbital (65 mg/kg). Transonic Doppler flow probes were placed around the superior mesenteric artery (SMA) and the abdominal aorta, and the animals were subjected to acute hemorrhage (or sham) to 30 mmHg for 90 min followed by 30 min of resuscitation with shed blood (n = 6/group). At 90, 105, and 120 min, sham animals in both anesthetic groups showed comparable blood pressures with a 50% decrease in SMA and aortic blood flow. Acute hemorrhage decreased SMA blood flow by 94.5 +/- 0.01 and 86.0 +/- 2.8%, respectively, in the pentobarbital and methoxyflurane groups, with similar changes occurring in aortic blood flow. During resuscitation, arterial pressure remained significantly depressed and SMA blood flow decreased by 65% in the pentobarbital group, whereas blood pressure returned to control levels and SMA blood flow increased to 56% of control values (P < 0.001) in the methoxyflurane group. The findings indicate that the choice of anesthetic agent may significantly impact splanchnic blood flow and needs to be taken into account when designing experiments examining effects of hemorrhagic shock.

scholarly journals Release mechanisms of major DAMPs

APOPTOSIS ◽  
2021 ◽  
Vol 26 (3-4) ◽  
pp. 152-162
Author(s):  
Atsushi Murao ◽  
Monowar Aziz ◽  
Haichao Wang ◽  
Max Brenner ◽  
Ping Wang
Keyword(s):  
Rna Binding ◽  
High Mobility ◽  
Live Cells ◽  
Membrane Channel ◽  
Membrane Rupture ◽  
Underlying Mechanisms ◽  
Shock Proteins ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Secretory Lysosomes

AbstractDamage-associated molecular patterns (DAMPs) are endogenous molecules which foment inflammation and are associated with disorders in sepsis and cancer. Thus, therapeutically targeting DAMPs has potential to provide novel and effective treatments. When establishing anti-DAMP strategies, it is important not only to focus on the DAMPs as inflammatory mediators but also to take into account the underlying mechanisms of their release from cells and tissues. DAMPs can be released passively by membrane rupture due to necrosis/necroptosis, although the mechanisms of release appear to differ between the DAMPs. Other types of cell death, such as apoptosis, pyroptosis, ferroptosis and NETosis, can also contribute to DAMP release. In addition, some DAMPs can be exported actively from live cells by exocytosis of secretory lysosomes or exosomes, ectosomes, and activation of cell membrane channel pores. Here we review the shared and DAMP-specific mechanisms reported in the literature for high mobility group box 1, ATP, extracellular cold-inducible RNA-binding protein, histones, heat shock proteins, extracellular RNAs and cell-free DNA.

Abstract 288: High Mobility Group Box 1 (HMGB1) is Involved in the Physiopathology of Post-Cardiac Arrest Syndrome

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Emilie Boissady ◽  
Cynthia El Hedjaj ◽  
Matthias Kohlhauer ◽  
Bijan Ghaleh ◽  
Renaud Tissier
Keyword(s):  
Cardiac Arrest ◽  
High Mobility ◽  
Brain Regions ◽  
Clinical Parameter ◽  
High Mobility Group ◽  
Neurological Dysfunction ◽  
Blood Levels ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Introduction: After cardiac arrest, a sepsis-like syndrome is observed and contributes to poor prognosis. Hypothesis: This syndrome could be provoked by the massive release of Damage Associated Molecular Patterns (DAMP). Our aim was to investigate the role of the High mobility group box 1 (HMGB1), a well-characterized nuclear DAMP, in an experimental model of cardiac arrest. Methods: Rabbits were anesthetized and submitted to 10 min of ventricular fibrillation. After resuscitation, they either received an administration of the inhibitor of HMGB1 release glycyrrhizin (4 mg/kg i.v.. (GL group, n=6), or saline (5 ml, i.v.; CT group, n=6). Two additional groups received glycyrrhizin (n=4) or saline (n=4) alone without cardiac arrest (Sham groups). Blood samples were withdrawn to evaluate the kinetics of HMGB1 release. After awakening, survival and neurological dysfunction were evaluated during 3 days. Animals were then euthanized and brain histologic damages were assessed (fluorojade-C staining). Results: In the Sham groups, glycyrrhizin did not modify hemodynamic nor clinical parameter as compared to saline. In the CT group, HMGB1 blood levels increased since 30 min after cardiac arrest and remained elevated until the end of the follow-up. This increase in HMGB1 concentrations was significantly attenuated in GL vs CR (18±1 vs 29±5 and ng/ml at 30 min after cardiac arrest, respectively). Neurological dysfunction score or survival were not significantly improved in GL vs CT (e.g., survival = 50 vs 33 % at day 3 in GT vs CT group). However, fluorojade C staining showed a dramatic attenuation of degenerating neurons in GL vs CT groups in all brain regions (e.g., 7±3 vs 32±10 neurons/field in cortex, respectively). Conclusion: HMGB1 played a key role in early inflammation and promoted neuronal death after cardiac arrest. Its inhibition alone does not provide sufficient benefits to improve the clinical outcome. It emphasizes the importance of other contributors, beyond inflammation and neurons cell death. Adjunction of HMGB1 inhibitors to other therapies could still be of interest.

scholarly journals Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization, in Possible Relation to Damage-Associated Molecular Patterns and Autophagy

2020 ◽  
Vol 21 (23) ◽  
pp. 8998
Author(s):  
Yuka Tsuji ◽  
Mizuki Kuramochi ◽  
Hossain M. Golbar ◽  
Takeshi Izawa ◽  
Mitsuru Kuwamura ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Rat Model ◽  
Tissue Injury ◽  
Macrophage Polarization ◽  
Coagulation Necrosis ◽  
M2 Macrophage ◽  
Old Rats ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
M1 Type

Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver samples from six-week-old rats injected with APAP (1000 mg/kg BW, ip, once) after 15 h fasting were collected at hour 10, and on days 1, 2, 3, and 5. Liver lesions consisting of coagulation necrosis and inflammation were seen in the affected centrilobular area on days 1 and 2, and then, recovered with reparative fibrosis by day 5. Liver exudative enzymes increased transiently on day 1. CD68+ M1-macrophages increased significantly on days 1 and 2 with increased mRNAs of M1-related cytokines such as IFN-g and TNF-α, whereas CD163+ M2-macrophages appeared later on days 2 and 3. Macrophages reacting to MHC class II and Iba1 showed M1-type polarization, and CD204+ macrophages tended to be polarized toward M2-type. At hour 10, interestingly, HMGB1 (representative DAMPs) and its related signals, TLR-9 and MyD88, as well as LC3B+ autophagosomes began to increase. Collectively, the pathogenesis of rat APAP hepatotoxicity, which is the first, detailed report for a rat model, might be influenced by macrophage functions of M1 type for tissue injury/inflammation and M2-type for anti-inflammatory/fibrosis; particularly, M1-type may function in relation to DAMPs and autophagy. Understanding the interplayed mechanisms would provide new insight into hepato-pathogenesis and contribute to the possible development of therapeutic strategies.

scholarly journals Complement factor 3 deficiency attenuates hemorrhagic shock-related hepatic injury and systemic inflammatory response syndrome

2010 ◽  
Vol 299 (5) ◽  
pp. R1175-R1182 ◽  
Author(s):  
Changchun Cai ◽  
Roop Gill ◽  
Hyun-Ae Eum ◽  
Zongxian Cao ◽  
Patricia A. Loughran ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Hemorrhagic Shock ◽  
Complement Activation ◽  
Tissue Injury ◽  
Soft Tissue Injury ◽  
High Mobility ◽  
Organ Damage ◽  
Heme Oxygenase 1 ◽  
Complement Factor ◽  
Wild Type

Although complement activation is known to occur in the setting of severe hemorrhagic shock and tissue trauma (HS/T), the extent to which complement drives the initial inflammatory response and end-organ damage is uncertain. In this study, complement factor 3-deficient (C3−/−) mice and wild-type control mice were subjected to 1.5-h hemorrhagic shock, bilateral femur fracture, and soft tissue injury, followed by 4.5-h resuscitation (HS/T). C57BL/6 mice were also given 15 U of cobra venom factor (CVF) or phosphate-buffered saline injected intraperitoneally, followed by HS/T 24 h later. The results showed that HS/T resulted in C3 consumption in wild-type mice and C3 deposition in injured livers. C3−/− mice had significantly lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and circulating DNA levels, together with much lower circulating interleukin (IL)-6, IL-10, and high-mobility group box 1 (HMGB1) levels. Temporary C3 depletion by CVF preconditioning also led to reduced transaminases and a blunted cytokine release. C3−/− mice displayed well-preserved hepatic structure. C3−/− mice subjected to HS/T had higher levels of heme oxygenase-1, which has been associated with tissue protection in HS models. Our data indicate that complement activation contributes to inflammatory pathways and liver damage in HS/T. This suggests that targeting complement activation in the setting of severe injury could be useful.

scholarly journals Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury

2015 ◽  
Vol 308 (9) ◽  
pp. L855-L860 ◽  
Author(s):  
Robert Maile ◽  
Samuel Jones ◽  
Yinghao Pan ◽  
Haibo Zhou ◽  
Ilona Jaspers ◽  
...  
Keyword(s):  
North Carolina ◽  
Bacterial Infection ◽  
Injury Severity ◽  
Burn Injury ◽  
Tissue Injury ◽  
Cell Damage ◽  
Inhalation Injury ◽  
High Mobility Group Protein ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Bacterial infection is a major cause of morbidity affecting outcome following burn and inhalation injury. While experimental burn and inhalation injury animal models have suggested that mediators of cell damage and inflammation increase the risk of infection, few studies have been done on humans. This is a prospective, observational study of patients admitted to the North Carolina Jaycee Burn Center at the University of North Carolina who were intubated and on mechanical ventilation for treatment of burn and inhalational injury. Subjects were enrolled over a 2-yr period and followed till discharge or death. Serial bronchial washings from clinically indicated bronchoscopies were collected and analyzed for markers of tissue injury and inflammation. These include damage-associated molecular patterns (DAMPs) such as hyaluronic acid (HA), double-stranded DNA (dsDNA), heat-shock protein 70 (HSP-70), and high-mobility group protein B-1 (HMGB-1). The study population was comprised of 72 patients who had bacterial cultures obtained for clinical indications. Elevated HA, dsDNA, and IL-10 levels in bronchial washings obtained early (the first 72 h after injury) were significantly associated with positive bacterial respiratory cultures obtained during the first 14 days postinjury. Independent of initial inhalation injury severity and extent of surface burn, elevated levels of HA dsDNA and IL-10 in the central airways obtained early after injury are associated with subsequent positive bacterial respiratory cultures in patients intubated after acute burn/inhalation injury.

Alarmins at the maternal–fetal interface: involvement of inflammation in placental dysfunction and pregnancy complications

2019 ◽  
Vol 97 (3) ◽  
pp. 206-212 ◽  
Author(s):  
Marie-Eve Brien ◽  
Bernadette Baker ◽  
Cyntia Duval ◽  
Virginie Gaudreault ◽  
Rebecca L. Jones ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Deoxyribonucleic Acid ◽  
High Mobility ◽  
Placental Dysfunction ◽  
Current State ◽  
Hofbauer Cells ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
In Pregnancy

Inflammation is known to be associated with placental dysfunction and pregnancy complications. Infections are well known to be a cause of inflammation but they are frequently undetectable in pregnancy complications. More recently, the focus has been extended to inflammation of noninfectious origin, namely caused by endogenous mediators known as “damage-associated molecular patterns (DAMPs)” or alarmins. In this manuscript, we review the mechanism by which inflammation, sterile or infectious, can alter the placenta and its function. We discuss some classical DAMPs, such as uric acid, high mobility group box 1 (HMGB1), cell-free fetal deoxyribonucleic acid (DNA) (cffDNA), S100 proteins, heat shock protein 70 (HSP70), and adenosine triphosphate (ATP) and their impact on the placenta. We focus on the main placental cells (i.e., trophoblast and Hofbauer cells) and describe the placental response to, and release of, DAMPs. We also covered the current state of knowledge about the role of DAMPs in pregnancy complications including preeclampsia, fetal growth restriction, preterm birth, and stillbirth and possible therapeutic strategies to preserve placental function.

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