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 Cecal ligation and puncture accelerates development of ventilator-induced lung injury

2015 ◽  
Vol 308 (5) ◽  
pp. L443-L451 ◽  
Author(s):  
Nadir Yehya ◽  
Yi Xin ◽  
Yousi Oquendo ◽  
Maurizio Cereda ◽  
Rahim R. Rizi ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Mechanical Ventilation ◽  
Lung Injury ◽  
Pulmonary Inflammation ◽  
Cecal Ligation ◽  
Interleukin 1Β ◽  
Sham Operation ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Ventilator Induced Lung Injury

Sepsis is a leading cause of respiratory failure requiring mechanical ventilation, but the interaction between sepsis and ventilation is unclear. While prior studies demonstrated a priming role with endotoxin, actual septic animal models have yielded conflicting results regarding the role of preceding sepsis on development of subsequent ventilator-induced lung injury (VILI). Using a rat cecal ligation and puncture (CLP) model of sepsis and subsequent injurious ventilation, we sought to determine if sepsis affects development of VILI. Adult male Sprague-Dawley rats were subject to CLP or sham operation and, after 12 h, underwent injurious mechanical ventilation (tidal volume 30 ml/kg, positive end-expiratory pressure 0 cmH2O) for either 0, 60, or 120 min. Biochemical and physiological measurements, as well as computed tomography, were used to assess injury at 0, 60, and 120 min of ventilation. Before ventilation, CLP rats had higher levels of alveolar neutrophils and interleukin-1β. After 60 min of ventilation, CLP rats had worse injury as evidenced by increased alveolar inflammation, permeability, respiratory static compliance, edema, oxygenation, and computed tomography. By 120 min, CLP and sham rats had comparable levels of lung injury as assessed by many, but not all, of these metrics. CLP rats had an accelerated and worse loss of end-expiratory lung volume relative to sham, and consistently higher levels of alveolar interleukin-1β. Loss of aeration and progression of edema was more pronounced in dependent lung regions. We conclude that CLP initiated pulmonary inflammation in rats, and accelerated the development of subsequent VILI.

scholarly journals Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaozhu Zhai ◽  
Zhengfei Yang ◽  
Guanghui Zheng ◽  
Tao Yu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Troponin I ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
High Mobility ◽  
Dry Weight ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Potential Biomarker ◽  
Puncture Model

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

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.

scholarly journals Hypercapnic Acidosis Attenuates Lung Injury Induced by Established Bacterial Pneumonia

2008 ◽  
Vol 109 (5) ◽  
pp. 837-848 ◽  
Author(s):  
Martina Ni Chonghaile ◽  
Brendan D. Higgins ◽  
Joseph Costello ◽  
John G. Laffey
Keyword(s):  
Carbon Dioxide ◽  
Lung Injury ◽  
Antibiotic Therapy ◽  
Ischemia Reperfusion ◽  
Lung Compliance ◽  
In Vivo Model ◽  
Hypercapnic Acidosis ◽  
Sprague Dawley ◽  
E Coli

Background Hypercapnic acidosis protects against lung injury after ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. The effects of hypercapnic acidosis in the setting of established pulmonary sepsis are not known. The authors investigated whether hypercapnic acidosis -- induced by adding carbon dioxide to inspired gas -- would be beneficial or deleterious in established Escherichia coli pneumonia in an in vivo model, in the presence and absence of antibiotic therapy. Methods Adult male Sprague-Dawley rats were anesthetized and ventilated. In the first set of experiments, rats were anesthetized, E. coli (5-6.4 x 10(9)/ml colony-forming units) was instilled intratracheally, and the animals were allowed to recover. After 6 h, during which time a severe pneumonia developed, they were reanesthetized and randomly assigned to normocapnia (fraction of inspired carbon dioxide [Fico(2)] = 0.00, n = 10) or hypercapnic acidosis (Fico(2) = 0.05, n = 10). The second set of experiments was performed in a manner identical to that of series 1, but all rats (n = 10 per group) were given intravenous ceftriaxone (30 mg/kg) at randomization. All animals received normocapnia or hypercapnic acidosis for 6 h, and the severity of lung injury was assessed. Results In the absence of antibiotic therapy, hypercapnic acidosis reduced the pneumonia-induced increase in peak airway pressure and the decrease in static lung compliance compared with control conditions. In the presence of antibiotic therapy, which substantially reduced lung bacterial counts, hypercapnic acidosis significantly attenuated the extent of pneumonia-induced histologic injury. Conclusions Hypercapnic acidosis reduced the magnitude of the lung injury induced by established E. coli pneumonia.

Juglone Attenuates Sepsis-Induced Acute Lung Injury via Suppression of the TLR4/Nf-κb Pathway

2020 ◽  
Vol 18 (2) ◽  
pp. 201-206
Author(s):  
Qiu Nan ◽  
Xu Xinmei ◽  
He Yingying ◽  
Fan Chengfen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Cecal Ligation ◽  
Myeloperoxidase Activity ◽  
Nuclear Factor ◽  
Cecal Ligation And Puncture ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa

Sepsis, with high mortality, induces deleterious organ dysfunction and acute lung injury. Natural compounds show protective effect against sepsis-induced acute lung injury. Juglone, a natural naphthoquinone, demonstrates pharmacological actions as a pro-apoptotic substrate in tumor treatment and anti-inflammation substrate in organ injury. In this study, the influence of juglone on sepsis-induced acute lung injury was investigated. First, a septic mice model was established via cecal ligation and puncture, and then verified via histopathological analysis of lung tissues, the wet/dry mass ratio and myeloperoxidase activity was determined. Cecal ligation and puncture could induce acute lung injury in septic mice, as demonstrated by alveolar damage and increase of wet/dry mass ratio and myeloperoxidase activity. However, intragastric administration juglone attenuated cecal ligation and puncture-induced acute lung injury. Secondly, cecal ligation and puncture-induced increase of inflammatory cells in bronchoalveolar lavage fluid was also alleviated by the administration of juglone. Similarly, the protective effect of juglone against cecal ligation and puncture-induced acute lung injury was accompanied by a reduction of pro-inflammatory factor secretion in bronchoalveolar lavage fluid and lung tissues. Cecal ligation and puncture could activate toll-like receptor 4/nuclear factor-kappa B signaling pathway, and administration of juglone suppressed toll-like receptor 4/nuclear factor-kappa B activation. In conclusion, juglone attenuated cecal ligation and puncture-induced lung damage and inflammatory response through inactivation of toll-like receptor 4/nuclear factor-kappa B, suggesting a potential therapeutic strategy in the treatment of sepsis-induced acute lung injury.

Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

2019 ◽  
Vol 18 (2) ◽  
pp. 176-182
Author(s):  
Chen Weiyan ◽  
Deng Wujian ◽  
Chen Songwei
Keyword(s):  
Acute Lung Injury ◽  
B Cells ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Light Chain ◽  
Cecal Ligation ◽  
Nuclear Factor ◽  
Kappa Light Chain ◽  
Cecal Ligation And Puncture ◽  
Light Chain Enhancer

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney

2006 ◽  
Vol 290 (5) ◽  
pp. F1034-F1043 ◽  
Author(s):  
Tarek M. El-Achkar ◽  
Xiaoping Huang ◽  
Zoya Plotkin ◽  
Ruben M. Sandoval ◽  
Georges J. Rhodes ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Expression Patterns ◽  
Cecal Ligation ◽  
Proximal Tubules ◽  
Microbial Pathogens ◽  
Sprague Dawley ◽  
Renal Vasculature ◽  
Two Photon Microscopy ◽  
Sprague Dawley Rats ◽  
Cellular Signal

Toll-like receptors (TLRs) are now recognized as the major receptors for microbial pathogens on cells of the innate immune system. Recently, TLRs were also identified in many organs including the kidney. However, the cellular distribution and role of these renal TLRs remain largely unknown. In this paper, we investigated the expression of TLR4 in a cecal ligation and puncture (CLP) model of sepsis in Sprague-Dawley rats utilizing fluorescence microscopy. In sham animals, TLR4 was expressed predominantly in Tamm-Horsfall protein (THP)-positive tubules. In CLP animals, TLR4 expression increased markedly in all tubules (proximal and distal), glomeruli, and the renal vasculature. The staining showed a strong apical distribution in all tubules. A moderately less intense cellular signal colocalized partially with the Golgi apparatus. In addition, kidneys from septic rats showed increased expression of CD14 and THP. They each colocalized strongly with TLR4, albeit in different tubular segments. We also imaged the kidneys of live septic animals with two-photon microscopy after fluorescent lipopolysaccharide (LPS) injection. Within 10 min, LPS was seen at the brush border of some proximal tubules. Within 60 min, LPS was fully cytoplasmic in proximal tubules. Conversely, distal tubules showed no LPS uptake. We conclude that TLR4, CD14, and THP have specific renal cellular and tubular expression patterns that are markedly affected by sepsis. Systemic endotoxin can freely access the tubular and cellular sites where these proteins are present. Therefore, locally expressed TLRs and other interacting proteins could potentially modulate the renal response to systemic sepsis.

Ursolic acid improves survival and attenuates lung injury in septic rats induced by cecal ligation and puncture

2015 ◽  
Vol 194 (2) ◽  
pp. 528-536 ◽  
Author(s):  
Zhansheng Hu ◽  
Zhilong Gu ◽  
Meina Sun ◽  
Ke Zhang ◽  
Penghui Gao ◽  
...  
Keyword(s):  
Lung Injury ◽  
Ursolic Acid ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture
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