scholarly journals Pulmonary injury risk curves and behavioral changes from blast overpressure exposures of varying frequency and intensity in rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Venkatasivasai Sujith Sajja ◽  
Jonathan K. Statz ◽  
LCDR Peter B. Walker ◽  
Irene D. Gist ◽  
Donna M. Wilder ◽  
...  
Keyword(s):  
Lung Injury ◽  
Injury Risk ◽  
Behavioral Changes ◽  
Sprague Dawley ◽  
Injury Threshold ◽  
Blast Overpressure ◽  
Sprague Dawley Rats ◽  
Field Activity ◽  
Blast Lung Injury ◽  
The Military

Abstract At present, there are no set guidelines establishing cumulative limits for blast exposure numbers and intensities in military personnel, in combat or training operations. The objective of the current study was to define lung injury, pathology, and associated behavioral changes from primary repeated blast lung injury under appropriate exposure conditions and combinations (i.e. blast overpressure (BOP) intensity and exposure frequency) using an advanced blast simulator. Male Sprague Dawley rats were exposed to BOP frontally and laterally at a pressure range of ~ 8.5–19 psi, for up to 30 daily exposures. The extent of lung injury was identified at 24 h following BOP by assessing the extent of surface hemorrhage/contusion, Hematoxylin and Eosin staining, and behavioral deficits with open field activity. Lung injury was mathematically modeled to define the military standard 1% lung injury threshold. Significant levels of histiocytosis and inflammation were observed in pressures ≥ 10 psi and orientation effects were observed at pressures ≥ 13 psi. Experimental data demonstrated ~ 8.5 psi is the threshold for hemorrhage/contusion, up to 30 exposures. Modeling the data predicted injury risk up to 50 exposures with intensity thresholds at 8 psi for front exposure and 6psi for side exposures, which needs to be validated further.

Acute intranigral homocysteine administration produces stereotypic behavioral changes and striatal dopamine depletion in Sprague–Dawley rats

2006 ◽  
Vol 1075 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Goutam Chandra ◽  
Prasanta K. Gangopadhyay ◽  
Karuppagounder S. Senthil Kumar ◽  
Kochupurackal P. Mohanakumar
Keyword(s):  
Behavioral Changes ◽  
Striatal Dopamine ◽  
Dopamine Depletion ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Striatal Dopamine Depletion

scholarly journals Anthropomorphic Blast Test Device for Primary Blast Injury Risk Assessment

2020 ◽  
Vol 185 (Supplement_1) ◽  
pp. 227-233
Author(s):  
Yun Hsu ◽  
Kevin Ho ◽  
Philemon Chan
Keyword(s):  
Risk Assessment ◽  
Lung Injury ◽  
Open Field ◽  
Injury Risk ◽  
Health Hazard ◽  
Field Tests ◽  
Blast Injury ◽  
Test Device ◽  
Blast Overpressure ◽  
Lung Injuries

Abstract Introduction Blast overpressure health hazard assessment is required prior to fielding of weapon systems that produce blast overpressures that pose risk of auditory and nonauditory blast lung injuries. The anthropomorphic blast test device (ABTD) offers a single device solution for collection of both auditory and nonauditory data from a single blast at anthropometrically correct locations for injury risk assessment. It also allows for better replication of personnel positioning during weapons firings. The ABTD is an update of the blast test device (BTD), the current Army standard for collection of thoracic blast loading data. Validation testing of the ABTD is required to ensure that lung injury model validated using BTD collected test data and sheep subjects is still applicable when the ABTD is used. Methods Open field validation blast tests were conducted with BTD and ABTD placed at matching locations. Tests at seven blast strength levels were completed spanning the range of overpressures for occupational testing. Results The two devices produced very similar values for lung injury dose over all blast levels and orientations. Conclusion The ABTD was validated successfully for open field tests. For occupational blast injury assessments, ABTD can be used in place of the BTD and provide enhanced capabilities.

scholarly journals Activation of cholinergic anti-inflammatory pathway involved in therapeutic actions of α-mangostin on lipopolysaccharide-induced acute lung injury in rats

2020 ◽  
Vol 34 ◽  
pp. 205873842095494
Author(s):  
Zhe Yang ◽  
Qin Yin ◽  
Opeyemi Joshua Olatunji ◽  
Yan Li ◽  
Shu Pan ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Sprague Dawley ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Inflammatory Pathway ◽  
Inflammatory Reactions ◽  
Sprague Dawley Rats ◽  
Anti Inflammatory

Introduction: Alpha-mangostin (MAN) possesses a wide variety of pharmacological effects. In this study, we investigated its effect on cholinergic anti-inflammatory pathway (CAP), and tested if CAP regulation was involved in the therapeutic action on acute lung injury (ALI). Methods: Male Sprague Dawley rats were pre-treated with MAN (40 mg/kg) for 3 days and ALI was induced with an intraperitoneal injection of lipopolysaccharide (LPS). Certain rats received monolateral vagotomy or sham surgery. The effects on inflammatory reactions and relevant pathways in ALI rats or LPS pre-treated RAW 264.7 cells were investigated by histological, immunohistochemical, immunoblotting, RT-qPCR, and immunofluorescence assays, while levels of proinflammatory cytokines, acetylcholine (Ach) and the enzymatic activity of acetylcholinesterase (AchE) were determined by corresponding quantitative kits. Results: Oral administration of MAN reduced the severity of ALI, while vagotomy surgery antagonized this effect. MAN restored the decline in α7 nicotinic acetylcholine receptor (α7nAchR) in the lungs of ALI rats, and promoted the expression of α7nAchR and choline acetyltransferase (CHAT) in RAW 264.7 cells. Although AchE expression was barely affected by MAN at 5 μg/ml, its catalytic activity was reduced by almost 95%. Extracellular rather than intracellular Ach was notably raised shortly after MAN treatment. Furthermore, MAN at 5 μg/ml effectively inhibited LPS-induced increase in phosphorylation and nucleus translocation of p65 subunit, and secretion of TNF-α and IL-1β, which was then offset by methyllycaconitine citrate hydrate. Conclusion: MAN activated CAP by increasing peripheral Ach and up-regulating α7nAchR expression, which eventually led to NF-κB inhibition and remission of acute inflammations.

High-volume ventilation induces pentraxin 3 expression in multiple acute lung injury models in rats

2007 ◽  
Vol 292 (1) ◽  
pp. L144-L153 ◽  
Author(s):  
Daisuke Okutani ◽  
Bing Han ◽  
Marco Mura ◽  
Thomas K. Waddell ◽  
Shaf Keshavjee ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
High Volume ◽  
Pentraxin 3 ◽  
Sprague Dawley ◽  
Ventilator Induced Lung Injury ◽  
Sprague Dawley Rats ◽  
Volume Ventilation ◽  
Highly Correlated ◽  
Injury Models

Pentraxin 3 (PTX3) is an acute-phase protein, which can be produced by a variety of tissue cells at the site of infection or inflammation. It plays an important role in innate immunity in the lung and in mediating acute lung injury. The aim of this study was to determine the effect of mechanical ventilation on PTX3 expression in multiple lung injury models. Male Sprague-Dawley rats were challenged with intravenous injection of lipopolysaccharide (LPS) or hemorrhage followed by resuscitation (HS). The animals were then subjected to either relatively higher (12 ml/kg) or lower (6 ml/kg, positive end-expiratory pressure of 5 cmH2O) volume ventilation for 4 h. High-volume ventilation significantly enhanced PTX3 expression in the lung, either alone or in combination with LPS or hemorrhage. A significant increase of PTX3 immunohistochemistry staining in the lung was seen in all injury groups. The PTX3 expression was highly correlated with the severity of lung injury determined by blood gas, lung elastance, and wet-to-dry ratio. To determine the effects of HS, LPS, or injurious ventilation (25 ml/kg) alone on PTX3 expression, another group of rats was studied. Injurious ventilation significantly damaged the lung and increased PTX3 expression. A local expression of PTX3 induced by high-volume ventilation, either alone or in combination with other pathological conditions, suggests that it may be an important mediator in ventilator-induced lung injury.

scholarly journals Differential Effects of Buffered Hypercapnia versus  Hypercapnic Acidosis on Shock and Lung Injury Induced by Systemic Sepsis

2009 ◽  
Vol 111 (6) ◽  
pp. 1317-1326 ◽  
Author(s):  
Brendan D. Higgins ◽  
Joseph Costello ◽  
Maya Contreras ◽  
Patrick Hassett ◽  
Daniel O' Toole ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Lung Injury ◽  
Cecal Ligation ◽  
Hypercapnic Acidosis ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Systemic Sepsis ◽  
Sprague Dawley Rats ◽  
Hemodynamic Deterioration ◽  
Hemodynamic Profile

Background Acute hypercapnic acidosis protects against lung injury caused by nonseptic insults and after both pulmonary and systemic sepsis. The authors wished to dissect the contribution of the acidosis versus hypercapnia per se to the effects of hypercapnic acidosis on the hemodynamic profile and severity of lung injury induced by systemic sepsis. Methods In the hypercapnic acidosis series, adult male Sprague-Dawley rats were randomized to normocapnia or hypercapnic acidosis-produced by adding 5% carbon dioxide to the inspired gas-and cecal ligation and puncture performed. In the buffered hypercapnia series, animals were first randomized to housing under conditions of environmental normocapnia or hypercapnia-produced by exposure to 8% carbon dioxide-to allow renal buffering. After 96 h, cecal ligation and puncture was performed. In both series, the animals were ventilated for 6 h, and the severity of the lung injury and hemodynamic deterioration were assessed. Results Both hypercapnic acidosis and buffered hypercapnia attenuated the development and severity of hypotension and reduced lactate accumulation compared to normocapnia. Hypercapnic acidosis reduced lung injury and inflammation, decreased mean (+ or - SD) bronchoalveolar lavage protein concentration (232 + or - 50 versus 279 + or - 27 microg x ml(-1)) and median neutrophil counts (3,370 versus 9,120 cells x ml(-1)), and reduced histologic lung injury. In contrast, buffered hypercapnia did not reduce the severity of systemic sepsis induced lung injury. Conclusions Both hypercapnic acidosis and buffered hypercapnia attenuate the hemodynamic consequences of systemic sepsis. In contrast, hypercapnic acidosis, but not buffered hypercapnia, reduced the severity of sepsis-induced lung injury.

scholarly journals Comparison of direct and indirect models of early induced acute lung injury

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Laura Chimenti ◽  
Luis Morales-Quinteros ◽  
Ferranda Puig ◽  
Marta Camprubi-Rimblas ◽  
Raquel Guillamat-Prats ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Acute Phase ◽  
Cecal Ligation ◽  
Sprague Dawley ◽  
Acid Aspiration ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Gastric Contents ◽  
Bacterial Superinfection

Abstract Background The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. Aim To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS. Materials and methods Adult male Sprague-Dawley rats were subjected to intratracheal instillations of (1) HCl to mimic aspiration of gastric contents; (2) lipopolysaccharide (LPS) to mimic bacterial infection; (3) HCl followed by LPS to mimic aspiration of gastric contents with bacterial superinfection; or (4) cecal ligation and puncture (CLP) to induce peritonitis and mimic sepsis. Rats were sacrificed 24 h after instillations or 24 h after CLP. Results At 24 h, rats instilled with LPS or HCl-LPS had increased lung permeability, alveolar neutrophilic recruitment and inflammatory markers (GRO/KC, TNF-α, MCP-1, IL-1β, IL-6). Rats receiving only HCl or subjected to CLP had no evidence of lung injury. Conclusions Rat models of ALI induced directly by LPS or HCl-LPS more closely reproduced the acute phase of human ARDS than the CLP model of indirectly induced ALI.

Hemorrhagic shock induces G-CSF expression in bronchial epithelium

1997 ◽  
Vol 273 (5) ◽  
pp. L1058-L1064 ◽  
Author(s):  
Christian Hierholzer ◽  
Edward Kelly ◽  
Katsuhiko Tsukada ◽  
Eric Loeffert ◽  
Simon Watkins ◽  
...  
Keyword(s):  
Lung Injury ◽  
Hemorrhagic Shock ◽  
Fold Increase ◽  
Bronchial Epithelium ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Inflammatory Processes ◽  
Csf Levels

Hemorrhagic shock (HS) initiates a series of inflammatory processes that includes the activation of polymorphonuclear granulocytic neutrophils (PMN). We tested the hypothesis that HS induces granulocyte colony-stimulating factor (G-CSF), a cytokine that augments PMN effector functions, in the lungs of rats. Sprague-Dawley rats were subjected to compensated or decompensated HS followed by resuscitation and death at 4 or 8 h. Animals subjected to HS demonstrated acute lung injury with PMN infiltration, edema, and hypoxia. Using semiquantitative reverse transcriptase-polymerase chain reaction, we detected a 1.9- to 7.1-fold increase in G-CSF mRNA levels in the lung of animals subjected to HS compared with sham controls. Levels of G-CSF mRNA increased with increased duration of the ischemic phase of resuscitated shock. In situ hybridization revealed that bronchoepithelial cells were the major cellular site of G-CSF mRNA. Thus production of G-CSF mRNA by bronchoepithelial cells is dramatically increased in a rat model of HS that also demonstrated lung injury. Increased local G-CSF levels may contribute to PMN recruitment and activation and resultant lung injury in HS.

Finite Element Modeling of Blast Lung Injury in Sheep

2015 ◽  
Vol 137 (4) ◽  
Author(s):  
Melissa M. Gibbons ◽  
Xinglai Dang ◽  
Mark Adkins ◽  
Brian Powell ◽  
Philemon Chan
Keyword(s):  
Finite Element ◽  
Lung Injury ◽  
Plastic Material ◽  
Field Testing ◽  
Material Model ◽  
Threshold Value ◽  
Element Model ◽  
Blast Overpressure ◽  
Strain And Strain Rate ◽  
Blast Lung Injury

A detailed 3D finite element model (FEM) of the sheep thorax was developed to predict heterogeneous and volumetric lung injury due to blast. A shared node mesh of the sheep thorax was constructed from a computed tomography (CT) scan of a sheep cadaver, and while most material properties were taken from literature, an elastic–plastic material model was used for the ribs based on three-point bending experiments performed on sheep rib specimens. Anesthetized sheep were blasted in an enclosure, and blast overpressure data were collected using the blast test device (BTD), while surface lung injury was quantified during necropsy. Matching blasts were simulated using the sheep thorax FEM. Surface lung injury in the FEM was matched to pathology reports by setting a threshold value of the scalar output termed the strain product (maximum value of the dot product of strain and strain-rate vectors over all simulation time) in the surface elements. Volumetric lung injury was quantified by applying the threshold value to all elements in the model lungs, and a correlation was found between predicted volumetric injury and measured postblast lung weights. All predictions are made for the left and right lungs separately. This work represents a significant step toward the prediction of localized and heterogeneous blast lung injury, as well as volumetric injury, which was not recorded during field testing for sheep.

scholarly journals The Effect of Mechanical Ventilation on TASK-1 Expression in the Brain in a Rat Model

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Buqi Na ◽  
Hong Zhang ◽  
Guangfa Wang ◽  
Li Dai ◽  
Guoguang Xia
Keyword(s):  
Mechanical Ventilation ◽  
Brain Injury ◽  
Lung Injury ◽  
Rat Model ◽  
Central Control ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Lung Histology ◽  
Respiratory Centre ◽  
The Brain

Background and Objective. TWIK-related acid-sensitive potassium channel 1 (TASK-1) is closely related to respiratory central control and neuronal injury. We investigated the effect of MV on TASK-1’s functions and explored the mechanism using a rat model.Methods. Male Sprague-Dawley rats were randomized to three groups:(1)high tidal volume (HVt): MV for four hours with Vt at 10 mL/kg;(2)low Vt (LVt): MV for four hours with Vt at 5 mL/kg;(3)basal (BAS): anesthetized and unventilated animals. We measured lung histology and plasma and brain levels of proteins (IL-6, TNF-α, and S-100B) and determined TASK-1 levels in rat brainstems as a marker of respiratory centre activity.Results. The LISs (lung injury scores) were significantly higher in the HVt group. Brain inflammatory cytokines levels were different to those in serum. TASK-1 levels were significantly lower in the MV groups (P=0.002) and the HVt group tended to have a lower level of TASK-1 than the LVt group.Conclusion. MV causes not only lung injury, but also brain injury. MV affects the regulation of the respiratory centre, perhaps causing damage to it. Inflammation is probably not the main mechanism of ventilator-related brain injury.

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