High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep

2003 ◽  
Vol 104 (4) ◽  
pp. 349 ◽  
Author(s):  
Kazunori MURAKAMI ◽  
Perenlei ENKHBAATAR ◽  
Katsumi SHIMODA ◽  
Akio MIZUTANI ◽  
Robert A. COX ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Smoke Inhalation ◽  
High Dose ◽  
Dose Heparin

High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep

2003 ◽  
Vol 104 (4) ◽  
pp. 349-356 ◽  
Author(s):  
Kazunori MURAKAMI ◽  
Perenlei ENKHBAATAR ◽  
Katsumi SHIMODA ◽  
Akio MIZUTANI ◽  
Robert A. COX ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
High Dose ◽  
Heparin Infusion ◽  
Infusion Group ◽  
Dose Heparin ◽  
Lung Dysfunction

Thrombin is involved in various inflammatory responses. In sepsis, coagulation abnormalities are major complications. Acute lung injury is one of the most life-threatening problems that can result from sepsis. We hypothesized that high-dose heparin might be effective in attenuating acute lung injury in our sepsis model. Female sheep (n = 16) were surgically prepared for the study. After a tracheotomy, 48 breaths of cotton smoke (<40°C) were insufflated into the airway. Afterwards, live Pseudomonas aeruginosa (5×1011 colony-forming units) bacteria were instilled into the lung. All sheep were ventilated mechanically with 100% O2, and were divided into three groups: a heparin infusion group (n = 6), a Ringer's lactate infusion group (n = 6), and a sham-injury group (n = 4; surgically prepared in the same fashion but receiving no inhalation injury or bacteria). The treatment was started 1h after the insult, and was continued thereafter for 24h. The dose of heparin was adjusted by monitoring to target an activated clotting time of between 300 and 400s (baseline = approx. 150s). Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes, including an increased cardiac output and a fall in systemic vascular resistance. There was a decrease in the arterial partial pressure of O2. In conclusion, high-dose heparin did not prevent lung dysfunction in this model, in which acute lung injury was induced by combined smoke and septic challenge.

scholarly journals Rat model of smoke inhalation-induced acute lung injury

2021 ◽  
Vol 8 (1) ◽  
pp. e000879
Author(s):  
Premila Devi Leiphrakpam ◽  
Hannah R Weber ◽  
Tobi Ogun ◽  
Keely L Buesing
Keyword(s):  
Animal Model ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Caspase 3 ◽  
Small Animal ◽  
Therapeutic Options ◽  
Smoke Inhalation ◽  
Small Animal Model ◽  
Injury Score ◽  
Confounding Variables

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

The differential expression of novel circular RNAs in an acute lung injury rat model caused by smoke inhalation

2017 ◽  
Vol 74 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Zhiqiang Ye ◽  
Xuhui Liu ◽  
Yuewu Yang ◽  
Xianling Zhang ◽  
Ting Yu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Differential Expression ◽  
Rat Model ◽  
Smoke Inhalation ◽  
Circular Rnas

scholarly journals GBT1118, a compound that increases the oxygen affinity of hemoglobin, improves survival in murine hypoxic acute lung injury

2018 ◽  
Vol 124 (4) ◽  
pp. 899-905 ◽  
Author(s):  
Nathan D. Putz ◽  
Ciara M. Shaver ◽  
Kobina Dufu ◽  
Chien-Ming Li ◽  
Qing Xu ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Oxygen Affinity ◽  
High Dose ◽  
Novel Therapy ◽  
Oxygen Affinity Of Hemoglobin

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and pulmonary edema, leading to arterial hypoxemia and death if the hypoxemia is severe. Strategies to correct hypoxemia have the potential to improve clinical outcomes in ARDS. The goal of this study was to evaluate the potential of hemoglobin modification as a novel therapy for ARDS-induced hypoxemia. The therapeutic effect of two different doses of GBT1118, a compound that increases the oxygen affinity of hemoglobin, was evaluated in a murine model of acute lung injury induced by intratracheal LPS instillation 24 h before exposure to 5% or 10% hypoxia ( n = 8–15 per group). As expected, administration of GBT1118 to mice significantly increased the oxygen affinity of hemoglobin. Compared with mice receiving vehicle control, mice treated with GBT1118 had significantly lower mortality after LPS + 5% hypoxia (47% with vehicle vs. 22% with low-dose GBT1118, 13% with high-dose GBT1118, P = 0.032 by log rank) and had reduced severity of illness. Mice treated with GBT1118 showed a sustained significant increase in SpO2 over 4 h of hypoxia exposure. Treatment with GBT1118 did not alter alveolar-capillary permeability, bronchoalveolar lavage (BAL) inflammatory cell counts, or BAL concentrations of IL-1β, TNF-α, or macrophage inflammatory protein-1α. High-dose GBT1118 did not affect histological lung injury but did decrease tissue hypoxia as measured intensity of pimonidazole (Hypoxyprobe) staining in liver ( P = 0.043) and kidney ( P = 0.043). We concluded that increasing the oxygen affinity of hemoglobin using GBT1118 may be a novel therapy for treating hypoxemia associated with acute lung injury. NEW & NOTEWORTHY In this study, we show that GBT1118, a compound that increases hemoglobin affinity for oxygen, improves survival and oxygen saturation in a two-hit lung injury model of intratracheal LPS without causing tissue hypoxia. Modulation of hemoglobin oxygen affinity represents a novel therapeutic approach to treatment of acute lung injury and acute respiratory distress syndrome, conditions characterized by hypoxemia.

scholarly journals Methotrexate induced lung injury in a patient with primary CNS lymphoma: A case report

2012 ◽  
Vol 4 (1) ◽  
pp. e2012020 ◽  
Author(s):  
Puneet Chhabra ◽  
Arjun Dutt law ◽  
Dr vikas Suri ◽  
Dr pankaj Malhotra ◽  
Dr subhash Varma
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Rare Event ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Connective Tissue Disorders ◽  
High Dose Regimen ◽  
Dose Methotrexate

Methotrexate is an antimetabolite commonly used in clinical practice for a variety of indications ranging from rheumatoid arthritis and other connective tissue disorders to high dose regimens in many malignancies. This folate antagonist has got a spectrum of toxicities among which gastrointestinal effects predominate . Lung injury is a well described but rare event and has been reported most often in patients who have been on long term oral therapy for rheumatic disorders. Acute lung injury in a patient receiving a high dose regimen for haematological malignancies has not been reported previously. We present one such case of methotrexate related acute lung injury in a patient of primary CNS lymphoma receiving high dose methotrexate.

scholarly journals Propofol Activation of the Nrf2 Pathway Is Associated with Amelioration of Acute Lung Injury in a Rat Liver Transplantation Model

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Weifeng Yao ◽  
Gangjian Luo ◽  
Guosong Zhu ◽  
Xinjin Chi ◽  
Ailan Zhang ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Water Content ◽  
High Dose ◽  
Lung Pathology ◽  
Lung Water ◽  
Sod Activity ◽  
Nrf2 Pathway ◽  
Lung Water Content

Objective. This study aimed to investigate whether propofol pretreatment can protect against liver transplantation-induced acute lung injury (ALI) and to explore whether Nrf2 pathway is involved in the protections provided by propofol pretreatment.Method. Adult male Sprague-Dawley rats were divided into five groups based on the random number table. Lung pathology was observed by optical microscopy. Lung water content was assessed by wet/dry ratio, and PaO2was detected by blood gas analysis. The contents of H2O2, MDA, and SOD activity were determined by ELISA method, and the expression of HO-1, NQO1, Keap1, and nuclear Nrf2 was assayed by western blotting.Results. Compared with saline-treated model group, both propofol and N-acetylcysteine pretreatment can reduce the acute lung injury caused by orthotopic autologous liver transplantation (OALT), decrease the lung injury scores, lung water content, and H2O2and MDA levels, and improve the arterial PaO2and SOD activity. Furthermore, propofol (but not N-acetylcysteine) pretreatment especially in high dose inhibited the expression of Keap1 and induced translocation of Nrf2 into the nucleus to further upregulate the expression of HO-1 and NQO1 downstream.Conclusion. Pretreatment with propofol is associated with attenuation of OALT-induced ALI, and the Nrf2 pathway is involved in the antioxidative processes.

ACTIVATED PROTEIN C REDUCES COMBINED BURN AND SMOKE INHALATION-INDUCED ACUTE LUNG INJURY IN MICE BY INHIBITING EXCESSIVE PRODUCTION OF NITRIC OXIDE

2004 ◽  
Vol 32 (Supplement) ◽  
pp. A24 ◽  
Author(s):  
Akio Mizutani ◽  
Kazunori Murakami ◽  
Kenji Okajima ◽  
Takayuki Noguchi ◽  
Sachiko Mizutani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Protein C ◽  
Activated Protein C ◽  
Smoke Inhalation
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